Research activity information

• A novel splice site variant in TIMM8A induced abnormal mRNA splicing resulting in Mohr-Tranebjaerg syndrome.

  Hiroaki Hanafusa, Yusuke Ishida, Ryosuke Bo, Masahiro Nishiyama, Kandai Nozu, Hiroaki Nagase, Hiroyuki Awano

  BACKGROUND: Mohr-Tranebjaerg syndrome (MTS) is an X-linked recessive neurodegenerative disorder caused by pathogenic variants in TIMM8A. Of the 39 previously reported disease-causing variants in the TIMM8A, five are splice site variants; however, none of these variants have been evaluated by transcript analysis. METHODS: We performed panel-based targeted exome analysis in a Japanese boy with sensorineural hearing loss and rapidly progressive dystonia. To assess the effect of the identified splice donor site variant, transcript analysis was performed using RNA derived from peripheral blood. RESULT: A novel hemizygous splice donor site variant in TIMM8A (NM_004085.4:c.132+5G>A) was identified. Transcript analysis revealed three aberrant transcripts: two transcripts with partial intron 1 inclusion of 606 bp or 492 bp (INS606bp and INS492bp) and one transcript with a 60 bp partial deletion of exon 1 (Δ60bp), with no detectable normal transcript. Both INS606bp and INS492bp transcripts contain premature stop codons due to the inserted intronic sequences, leading to the loss of 53 amino acids, whereas the Δ60bp transcript leads to the loss of 20 amino acids. All aberrant transcripts lacked part of the Tim10/DDP family zinc finger domain, which is essential for TIM8A function. CONCLUSION: This study provides the first transcript analysis elucidating the pathogenic mechanism of a splice donor site variant in TIMM8A. The findings suggest that splice donor site variants may share a common disease mechanism involving the production of functionally defective TIM8A protein.

  Jun. 2026, Brain & development, 48(3) (3), 104525 - 104525, English, International magazine

  Scientific journal


• 兵庫県拡大マススクリーニングにおけるムコ多糖症2型の精密検査例の遺伝学的背景の検討 続報

  曽根原 晶子, 大橋 浩基, 洪 聖媛, 松井 美樹, 南部 静紀, 片岡 大, 李 知子, 粟野 宏之, 竹島 泰弘, 野津 寛大, 坊 亮輔

  (一社)日本マススクリーニング学会, Sep. 2025, 日本マス・スクリーニング学会誌, 35(2) (2), 235 - 235, Japanese


• 遺伝学的検査で診断に至った5例の発達遅滞・多発形態異常がある成人例における遺伝カウンセリング

  澤田 優貴, 花房 宏昭, 田中 敬子, 朝貝 芳貴, 坊 亮輔, 國久 智成, 久保 亮治, 永瀬 裕朗, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jul. 2025, 日本遺伝カウンセリング学会誌, 46(2) (2), 216 - 216, Japanese


• Incidence of Homozygous SMN2 Deletion in Japan: Cross-Reactivity of SMN2 Primers with SMN1 Sequence Causes False Negatives in Real-Time PCR Screening.

  Makoto Sakima, Yoshihiro Bouike, Shin-Ichi Wada, Masami Nakamae, Yoriko Noguchi, Ryosuke Bo, Hiroyuki Awano, Jumpei Oba, Hisahide Nishio

  Background: SMN1 and SMN2 are causative and modifier genes, respectively, for spinal muscular atrophy (SMA). The incidence of SMN1 homozygous deletion in Japan is 1 in 20,000. However, the incidence of SMN2 homozygous deletion in Japan remains unknown. Methods: To clarify the incidence of homozygous SMN2 deletion in Japan, real-time polymerase chain reaction (PCR) was performed on dried blood spot (DBS) samples collected from newborns nationwide. Samples with positive or ambiguous results were retested using PCR-restriction fragment length polymorphism (PCR-RFLP) and nucleotide sequence analysis. Results: Of the 1000 DBS samples that were screened using real-time PCR, 51 were positive. Retesting using PCR-RFLP analysis identified 10 false results: six false positives and four false negatives. Therefore, there were 49 true positives among the 1000 samples. Notably, nucleotide sequence analysis revealed that the false negatives were caused by the cross-reactivity of SMN2 primers with SMN1 sequences. Conclusions: The incidence of homozygous SMN2 deletion in Japan is approximately 1 in 20 people. This incidence is much higher than that of homozygous SMN1 deletion and may reflect the vulnerability of the SMN2 region. Importantly, the results of the present study suggest that false negatives in the screening process were caused by cross-reactivity with non-target gene sequences.

  Jun. 2025, Genes, 16(6) (6), English, International magazine

  Scientific journal


• 【小児外科疾患のQOL;最近の話題】胃瘻を有するデュシェンヌ型筋ジストロフィー症例

  光明 祐希, 大片 祐一, 粟野 宏之, 坊 亮輔, 尾藤 祐子

  (株)東京医学社, May 2025, 小児外科, 57(5) (5), 482 - 486, Japanese


• Fragmented QRS in Lateral Leads on Electrocardiography Is Associated with Cardiac Dysfunction and Left Ventricular Dilation in Duchenne Muscular Dystrophy.

  Tetsushi Yamamoto, Shuichiro Ogawa, Yusuke Ide, Kokoro Miyazaki, Aiko Sunami, Yoshinori Nambu, Ryosuke Bo, Masafumi Matsuo, Hiroyuki Awano

  Background/Objectives: Duchenne muscular dystrophy (DMD) is an X-linked inherited muscle disease. Patients with DMD demonstrate improved prognosis with angiotensin-converting enzyme inhibitors and beta-blockers at the time of cardiac dysfunction. However, most deaths due to DMD are due to cardiac dysfunction. Fragmented QRS (fQRS) is an abnormal finding that forms a notch in the QRS wave on electrocardiography (ECG) and is associated with fibrosis and scarring of the myocardium. Methods: Patients with DMD were examined for the number of leads of fQRS, their sites of appearance, changes in cardiac dysfunction, and age using the chest leads of a synthesized 18-ECG. A retrospective analysis of 184 patients under 20 years of age with DMD and known genetic mutations was performed; they were divided into three age groups: 3-10, 11-15, and 16-20 years. The chest leads of the ECG were defined as follows: V1-3, anterior leads; V4-6, lateral leads; V7-9, posterior leads; and V3R-V5R, right-sided chest leads. Cardiac dysfunction was defined as a left ventricular (LV) ejection fraction <53% on the same day, and echocardiography was performed. LV dilation was defined as dilation beyond the normal range, considering the body surface area. Results: In 167 of 184 patients (91%), fQRS was present in one or more chest leads. The number of fQRS leads in the anterior and lateral walls was significantly higher in 16-20-year-olds than in 3-10-year-olds. The total number of chest leads with fQRS was 4.9 ± 3.1 in the cardiac dysfunction group and 3.5 ± 2.5 in the preserved group. The cardiac dysfunction group had a significantly greater number of fQRS leads than did the preserved group (p = 0.003). The group with LV dilation had a significantly greater number of fQRS leads than did the non-dilation group (p = 0.009). Conclusions: The fQRS site is associated with age, cardiac dysfunction, and LV dilation. Multivariate regression analysis revealed that the number of anterior leads of the fQRS correlated with age and that of lateral leads of the fQRS with cardiac dysfunction and LV dilation. The number of fQRS leads on the lateral wall marks cardiac dysfunction and LV dilation.

  Mar. 2025, Biomedicines, 13(4) (4), English, International magazine

  Scientific journal


• Total Intramuscular Fat Fraction of Thigh Muscles as a Predictor of Nusinersen Efficacy in Pediatric SMA Type II and III.

  Kiiko Iketani, Hiroyuki Awano, Hiromi Hashimura, Shoko Sonehara, Hiroaki Hanafusa, Yoshinori Nambu, Hisahide Nishio, Kandai Nozu, Ryosuke Bo

  Background/Objectives: Nusinersen is a disease-modifying drug for spinal muscular atrophy (SMA) that improves motor function. However, its effects on the skeletal muscles remain unclear. This study aimed to assess the intramuscular fat fraction in patients with SMA types II and III using muscle magnetic resonance imaging (MRI) and to explore the relationship between muscle tissue, lipid metabolism, and motor function during nusinersen treatment. Methods: This study included seven pediatric patients with SMA types II and III who received nusinersen treatment. Muscle MRIs were performed at three time points. Images of the central thigh were used to measure the cross-sectional area (CSA) and muscle fat area, and the intramuscular fat fraction (IMFF) was calculated. The thigh muscles were categorized into three groups: quadriceps, adductor, and hamstrings. Results: The median (range) of total IMFF for SMA type II and III at T-0, T-2, and T-4 were 18.5 (12.6-48.4), 24.4 (10.1-61.4), and 39.0 (30.0-68.6) % and increased over time. In five patients whose motor function was evaluated, a moderate negative correlation was observed between the changes in the Hammersmith Functional Motor Score Expanded (HSFME) and IMFF (r = -0.51). No significant changes in serum triglyceride or total cholesterol levels were observed during treatment. Conclusions: An increase in IMFF was associated with a decline in motor function. The baseline IMFF score was related to improvements in motor function scores, suggesting that the IMFF of the thigh muscle may serve as a novel, objective, and quantitative skeletal muscle-related biomarker for predicting the effects of nusinersen on muscle tissue.

  Mar. 2025, Diagnostics (Basel, Switzerland), 15(6) (6), English, International magazine

  Scientific journal


• Epidemiology of SARS-CoV-2 Infection in Patients with Neuromuscular Disease and Inborn Errors of Metabolism: A Cross-sectional Study for a Pediatric Outpatient Referral in Japan.

  Sungwon Hong, Kiiko Iketani, Shoko Sonehara, Hiroaki Hanafusa, Yoshinori Nambu, Kandai Nozu, Hiroyuki Awano, Ryosuke Bo

  The coronavirus disease 2019 (COVID-19) pandemic has affected people worldwide, and pediatric patients with underlying diseases are at high risk of developing severe COVID-19. However, there are limited reports on the clinical impact of COVID-19, especially in patients with underlying neuromuscular diseases (NMD) and inborn errors of metabolism (IEM). This study aimed to investigate the incidence and clinical presentation of COVID-19 in patients with NMD and IEM. This was a single-center, cross-sectional study of patients with NMD and IEM in Japan for 2 years, from April 1, 2020 to March 31, 2022. Among 255 participants with a median age of 14 (range: 0-50) years, 192 (75%) and 63 (25%) had NMD and IEM, respectively. Among 255 patients, 8 (5 NMD and 3 IEM) were positive for the anti-severe acute respiratory syndrome coronavirus 2 nucleocapsid antibody, and the incidence was considered 3%. All positive patients had mild or asymptomatic COVID-19. None of the patients exhibited moderate or severe symptoms. In conclusion, this study revealed that the incidence of COVID-19 was low, and mild or subclinical infection was common even in patients with NMD and IEM, who may be at a higher risk of severe COVID-19.

  Feb. 2025, The Kobe journal of medical sciences, 70(4) (4), E106-E112, English, Domestic magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Fructose-1,6-bisphosphatase deficiency presenting with neonatal hyperlactatemia and elevated lactate-to-pyruvate ratio.

  Sanae Naito, Sachiyo Fukushima, Hiroaki Hanafusa, Tomoaki Ioroi, Hiroyuki Awano, Kandai Nozu, Ryosuke Bo

  2025, Pediatrics international : official journal of the Japan Pediatric Society, 67(1) (1), e70267, English, International magazine

  Scientific journal


• Serum titin/creatinine ratio as a biomarker for discriminating disease severity in Duchenne and Becker muscular dystrophies.

  Yoshinori Nambu, Kayo Osawa, Taku Shirakawa, Aiko Sunami, Shoko Sonehara, Ryosuke Bo, Kandai Nozu, Masafumi Matsuo, Hiroyuki Awano

  INTRODUCTION: Duchenne/Becker muscular dystrophies (DMD/BMD) are inherited muscle diseases, collectively referred to as dystrophinopathy, which are characterized by progressive degeneration or loss. Although serum creatine kinase (CK) is a classical biomarker of DMD and BMD, it alone cannot clearly differentiate between severe DMD and milder BMD. Among potential biomarkers, the levels of the fragmented products of titin, a structural muscle protein, may directly reflect the degree of muscle loss in DMD and BMD. Therefore, this study measured the serum titin/creatinine (Cr) ratio and evaluated its discriminatory ability in patients with DMD and BMD. METHODS: The patients with dystrophinopathy and healthy controls were included in this study. Patients were classified by the reading frame rule (out-of-frame, DMD; in-frame, BMD). Exceptional cases in which in-frame variants presented with severe symptoms or out-of-frame variants presented with mild symptoms were considered clinically DMD or clinically BMD, respectively. Serum titin levels were measured using enzyme-linked immunosorbent assay. Serum Cr levels measured on the same day were used to calculate serum titin/Cr ratios. RESULTS: The DMD, BMD, and control groups included 89 patients (85 DMD and four clinically DMD; aged 3-32 years), 21 patients (16 BMD and five clinically BMD; aged 6-33 years), and five participants (aged 7-12 years), respectively. Although serum CK levels did not differ significantly between DMD and BMD, the serum titin/Cr ratio in DMD was approximately 10 times higher than that in BMD group (p < 0.0001). Receiver operating characteristic curve analysis revealed that the ability of serum titin/Cr to distinguish DMD from BMD was superior to that of serum CK. Serum titin/Cr ratios in patients with DMD were higher than those with BMD across all age groups (3-10, 11-15, 16-20, and 21-33), but serum CK levels in patients with DMD were significantly higher than those with BMD only in the 11-15 and 21-33-year age groups. CONCLUSION: Unlike serum CK, the serum titin/Cr ratio in patients with DMD was consistently higher than that in patients with BMD, regardless of age. Serum titin/Cr was shown to be a biomarker to discriminate clinical severity in patients with dystrophinopathy.

  2025, Frontiers in neurology, 16, 1591748 - 1591748, English, International magazine

  Scientific journal


• 二次性頭痛の鑑別の中で発見し得た症状の乏しいもやもや病

  鮫島 智大, 山口 宏, 伊藤 立人, 川村 葵, 曽根原 晶子, 洪 聖媛, 花房 宏昭, 老川 静香, 徳元 翔一, 坊 亮輔, 永瀬 裕朗

  (一社)日本小児神経学会, Nov. 2024, 脳と発達, 56(6) (6), 460 - 460, Japanese


• Health-related quality of life and caregiver burden of pediatric patients with inborn errors of metabolism in Japan using EQ-5D-Y, PedsQL, and J-ZBI.

  Keiko Konomura, Chikahiko Numakura, Akari Nakamura-Utsunomiya, Eri Hoshino, Go Tajima, Hironori Kobayashi, Kimitoshi Nakamura, Nobuyuki Shimozawa, Ryosuke Bo, Takeru Shiroiwa, Yosuke Shigematsu, Takashi Fukuda

  PURPOSE: Inborn errors of metabolism (IEM) are known with poor long-term health concerns; however, the health-related quality of life (HRQoL) and the burden placed on families remain unclear. This study investigated the self- and proxy-reported HRQoL of pediatric patients with IEM with or without developmental disabilities and the burden placed on their caregivers. METHODS: Patients with IEM aged 8-15 years and their caregivers were asked to respond to the Pediatric Quality of Life Inventory (PedsQL), EuroQoL five-dimension questionnaire for younger populations (EQ-5D-Y), and Japanese version of the Zarit Caregiver Burden Interview (J-ZBI). We compared EQ-5D-Y scores with matched EQ-5D-Y population norms. Intraclass correlation coefficients (ICC) for self and proxy HRQoL scores of those without developmental disabilities were calculated. Correlation coefficients of HRQoL proxy responses with J-ZBI score were estimated. RESULTS: We included 66 patients with IEM (mean age, 11.5 years; males, 41.2%) in the study. The mean (± standard deviation) EQ-5D-Y scores without and with developmental disabilities were 0.957 (± 0.071) and 0.821 (± 0.175), respectively. The EQ-5D-Y scores significantly increased compared with the reference values (p < 0.01, effect size = 0.337). The ICC values were 0.331 and 0.477 for the EQ-5D-Y and PedsQL scores, respectively. HRQoL proxy scores had strong negative correlations with J-ZBI scores. CONCLUSION: The HRQoL of patients with IEM without developmental disabilities in our study was similar to that of the general Japanese population. The HRQoL of patients with IEM with developmental disabilities was low and associated with a tendency towards an increased burden of care.

  Sep. 2024, Quality of life research : an international journal of quality of life aspects of treatment, care and rehabilitation, English, International magazine

  Scientific journal


• 兵庫県/神戸市の拡大新生児マススクリーニングにおけるポンペ病精密検査例の遺伝学的背景と酵素活性の検討

  曽根原 晶子, 大橋 浩基, 松井 美樹, 花房 宏昭, 南部 静紀, 李 知子, 粟野 宏之, 竹島 泰弘, 野津 寛大, 坊 亮輔

  (一社)日本マススクリーニング学会, Jul. 2024, 日本マス・スクリーニング学会誌, 34(2) (2), 209 - 209, Japanese


• 兵庫県における拡大新生児マススクリーニングの現状

  武田 紗季, 李 知子, 柴田 暁男, 坊 亮輔, 山本 暢之, 上田 雅章, 粟野 宏之, 野津 寛大, 飯島 一誠, 竹島 泰弘

  (一社)日本周産期・新生児医学会, Jun. 2024, 日本周産期・新生児医学会雑誌, 60(Suppl.1) (Suppl.1), P282 - P282, Japanese


• Duchenne型筋ジストロフィー患者に対するプレドニゾロンの歩行能力への影響とACTN3遺伝型の関連

  佐伯 淳二郎, 南部 静紀, 曽根原 晶子, 花房 宏昭, 坊 亮輔, 野津 寛大, 粟野 宏之

  (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S236 - S236, Japanese


• Duchenne型筋ジストロフィー患者および保護者を対象とした「病気の説明」に関するアンケート調査

  八木 麻理子, 坊 亮輔, 粟野 宏之, 李 知子, 福井 美苗, 本田 順子, 竹島 泰弘

  (一社)日本小児神経学会, May 2024, 脳と発達, 56(Suppl.) (Suppl.), S256 - S256, Japanese


• 意識障害と片麻痺を繰り返した46,XX,der(18)t(12;18)(p11.2;p11.2)

  川村 葵, 山口 宏, 伊藤 立人, 曽根原 晶子, 洪 聖媛, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 坊 亮輔, 永瀬 裕朗

  (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 151 - 151, Japanese


• 持続する右下肢痛で発症した骨肉腫の1例

  伊藤 立人, 川村 葵, 曽根原 晶子, 西村 明紘, 洪 聖媛, 鮫島 智大, 花房 宏昭, 老川 静香, 徳元 翔一, 山口 宏, 坊 亮輔, 山本 暢之, 永瀬 裕朗

  (一社)日本小児神経学会, Mar. 2024, 脳と発達, 56(2) (2), 152 - 152, Japanese


• Response to: Is pancreatitis actually a phenotypic manifestation of Leigh syndrome?

  Kengo Nakashima, Ryosuke Bo, Hiroyuki Awano, Masahiro Nishiyama, Kazumoto Iijima

  2024, Pediatrics international : official journal of the Japan Pediatric Society, 66(1) (1), e15783, English, International magazine


• Newborn Screening for Spinal Muscular Atrophy: A 2.5-Year Experience in Hyogo Prefecture, Japan

  Shoko Sonehara, Ryosuke Bo, Yoshinori Nambu, Kiiko Iketani, Tomoko Lee, Hideki Shimomura, Masaaki Ueda, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hisahide Nishio, Hiroyuki Awano

  Newborn screening (NBS) for spinal muscular atrophy (SMA) is necessary, as favorable outcomes can be achieved by treatment with disease-modifying drugs in early infancy. Although SMA-NBS has been initiated in Japan, its clinical results have not been fully reported. We report the findings of the initial 2.5 years of a pilot SMA-NBS of approximately 16,000 infants conducted from February 2021 in Hyogo Prefecture, Japan. Clinical data of 17 infants who tested positive were retrospectively obtained from the NBS follow-up centers participating in this multicenter cohort observational study. Genetic testing revealed 14 false positives, and three infants were diagnosed with SMA. Case 1 had two copies of survival motor neuron (SMN) 2 and showed SMA-related symptoms at diagnosis. Case 2 was asymptomatic, with two copies of SMN2. Asymptomatic case 3 had four copies of SMN2 exon 7, including the SMN1/2 hybrid gene. Cases 1 and 2 were treated within 1 month and case 3 at 8 months. All the patients showed improved motor function scores and did not require respiratory support. The identification of infants with SMA via NBS and early treatment improved their motor and respiratory outcomes. Thus, implementation of SMA-NBS at a nationwide scale should be considered.

  MDPI AG, Dec. 2023, Genes, 14(12) (12), 2211 - 2211

  Scientific journal


• Electrocardiographic R wave amplitude in V6 lead as a predictive marker of cardiac dysfunction in Duchenne muscular dystrophy

  Tetsushi Yamamoto, Yoshinori Nambu, Ryosuke Bo, Shotaro Morichi, Misato Yanagiya, Masafumi Matsuo, Hiroyuki Awano

  Elsevier BV, Nov. 2023, Journal of Cardiology, 82(5) (5), 363 - 370

  Scientific journal


• 拡大新生児マススクリーニングで診断されたSMN2遺伝子4コピーのSMAに対して発症前治療を行った1例

  曽根原 晶子, 坊 亮輔, 洪 聖媛, 南部 静紀, 花房 宏昭, 李 知子, 竹島 泰弘, 西尾 久英, 粟野 宏之

  (一社)日本マススクリーニング学会, Aug. 2023, 日本マス・スクリーニング学会誌, 33(2) (2), 260 - 260, Japanese


• 拡大新生児マススクリーニングで診断されたSMN2遺伝子4コピーのSMAに対して発症前治療を行った1例

  曽根原 晶子, 坊 亮輔, 洪 聖媛, 南部 静紀, 花房 宏昭, 李 知子, 竹島 泰弘, 西尾 久英, 粟野 宏之

  (一社)日本マススクリーニング学会, Aug. 2023, 日本マス・スクリーニング学会誌, 33(2) (2), 260 - 260, Japanese


• 無精子症の精査を契機に染色分体早期解離(PCS)が判明した夫婦へ遺伝カウンセリングを行った1例

  田中 敬子, 花房 宏昭, 濱 真奈美, 千葉 公嗣, 坊 亮輔, 國久 智成, 久保 亮治, 粟野 宏之, 野津 寛大

  (一社)日本遺伝カウンセリング学会, Jun. 2023, 日本遺伝カウンセリング学会誌, 44(2) (2), 163 - 163, Japanese


• 拡大新生児マススクリーニングで発見された脊髄性筋萎縮症の2例

  曽根原 晶子, 坊 亮輔, 池谷 紀衣子, 南部 静紀, 老川 静香, 徳元 翔一, 山口 宏, 冨岡 和美, 永瀬 裕朗, 竹島 泰弘, 飯島 一誠, 野津 寛大, 西尾 久英, 粟野 宏之

  (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S319 - S319, Japanese


• ヌシネルセン治療を4年間行った脊髄性筋萎縮症3型の大腿MRIの変化

  池谷 紀衣子, 坊 亮輔, 曽根原 晶子, 花房 宏昭, 南部 静紀, 西尾 久英, 橋村 宏美, 粟野 宏之

  (一社)日本小児神経学会, May 2023, 脳と発達, 55(Suppl.) (Suppl.), S323 - S323, Japanese


• COVID-19感染症を契機に急性増悪した全身型重症筋無力症の女児例

  金谷 真吾, 岩本 宗矩, 山口 宏, 南部 静紀, 徳元 翔一, 坊 亮輔, 冨岡 和美, 西山 将広, 粟野 宏之, 野津 寛大, 永瀬 裕朗

  (公社)日本小児科学会, Apr. 2023, 日本小児科学会雑誌, 127(4) (4), 627 - 627, Japanese


• Correction: Noguchi et al. PCR-Based Screening of Spinal Muscular Atrophy for Newborn Infants in Hyogo Prefecture, Japan. Genes 2022, 13, 2110.

  Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hiroyuki Awano

  The authors wish to make the following correction to this paper [...].

  Mar. 2023, Genes, 14(3) (3), English, International magazine


• 妊娠中に成長ホルモン補充療法の再開を要したPIT-1異常症の1例

  辻本 泰貴, 坂東 弘教, 山本 雅昭, 大町 侑香, 本村 悠馬, 大井 佑夏, 佐々木 百合子, 山本 直希, 鈴木 正暉, 浦井 伸, 井口 元三, 高橋 路子, 栖田 園子, 尾崎 可奈, 出口 雅士, 洪 聖暖, 坊 亮輔, 粟野 宏之, 福岡 秀規, 小川 渉

  (一社)日本内分泌学会, Feb. 2023, 日本内分泌学会雑誌, 98(4) (4), 1035 - 1035, Japanese


• Clinical and molecular investigation of 37 Japanese patients with multiple acyl-CoA dehydrogenase deficiency: p.Y507D in ETFDH, a common Japanese variant, causes a mortal phenotype.

  Kenji Yamada, Yoshimitsu Osawa, Hironori Kobayashi, Ryosuke Bo, Yuichi Mushimoto, Yuki Hasegawa, Seiji Yamaguchi, Takeshi Taketani

  Multiple acyl-CoA dehydrogenase deficiency (MADD) is an inherited metabolic disease caused by a defect in electron transfer flavoprotein alpha (ETFA), ETF beta (ETFB), or ETF dehydrogenase (ETFDH), and riboflavin metabolism disorders have recently been reported to present as mimicking MADD. MADD is roughly classified into neonatal (type 1 or 2) and later-onset (type 3) forms. To identify clinicogenetic characteristics in Japan, we investigated 37 Japanese patients with MADD diagnosed from 1997 to 2020. The causes of MADD were ETFDH deficiency in 26 patients, ETFA deficiency in four, ETFB deficiency in six, and riboflavin metabolism disorder in one. All 15 patients with the neonatal-onset type died by 2 years of age, while five of 22 patients with the later-onset form died by 3 years of age. Furthermore, 8 of 15 patients with the later-onset form of ETFDH deficiency treated with riboflavin were riboflavin non-responders. p.Y507D in ETFDH was identified as the most common variant (9 of 48 alleles, 18.8%). Of two patients with a homozygous p.Y507D variant, one experienced disease onset and died in the neonatal period, while the other experienced disease onset at two months of age and died at two years old, suggesting that the p.Y507D variant results in fatal outcomes. Our study concluded that more than half of Japanese patients with MADD died by three years old, and more than half of patients with the later-onset form had poor responsiveness to riboflavin, partly due to the unique Japanese p.Y507D variant in ETFDH.

  Dec. 2022, Molecular genetics and metabolism reports, 33, 100940 - 100940, English, International magazine

  Scientific journal


• PCR-Based Screening of Spinal Muscular Atrophy for Newborn Infants in Hyogo Prefecture, Japan.

  Yoriko Noguchi, Ryosuke Bo, Hisahide Nishio, Hisayuki Matsumoto, Keiji Matsui, Yoshihiko Yano, Masami Sugawara, Go Ueda, Yogik Onky Silvana Wijaya, Emma Tabe Eko Niba, Masakazu Shinohara, Yoshihiro Bouike, Atsuko Takeuchi, Kentaro Okamoto, Toshio Saito, Hideki Shimomura, Tomoko Lee, Yasuhiro Takeshima, Kazumoto Iijima, Kandai Nozu, Hiroyuki Awano

  Spinal muscular atrophy (SMA) is a common devastating neuromuscular disorder, usually involving homozygous deletion of the SMN1 gene. Newly developed drugs can improve the motor functions of infants with SMA when treated in the early stage. To ensure early diagnosis, newborn screening for SMA (SMA-NBS) via PCR-based genetic testing with dried blood spots (DBSs) has been spreading throughout Japan. In Hyogo Prefecture, we performed a pilot study of SMA-NBS to assess newborn infants who underwent routine newborn metabolic screening between February 2021 and August 2022. Hyogo Prefecture has ~40,000 live births per year and the estimated incidence of SMA is 1 in 20,000-25,000 based on genetic testing of symptomatic patients with SMA. Here, we screened 8336 newborns and 12 screen-positive cases were detected by real-time PCR assay. Multiplex ligation-dependent probe amplification assay excluded ten false positives and identified two patients. These false positives might be related to the use of heparinized and/or diluted blood in the DBS sample. Both patients carried two copies of SMN2, one was asymptomatic and the other was symptomatic at the time of diagnosis. SMA-NBS enables us to prevent delayed diagnosis of SMA, even if it does not always allow treatment in the pre-symptomatic stage.

  Nov. 2022, Genes, 13(11) (11), English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• シトルリン低値による遅発型OTC欠損症・CPS1欠損症に対する新生児スクリーニング

  李 知子, 上田 雅章, 坊 亮輔, 粟野 宏之, 竹島 泰弘

  (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 187 - 187, Japanese


• 死亡時のアシルカルニチン分析結果を契機に確定診断したグルタル酸血症2型の一例

  坊 亮輔, 池谷 紀衣子, 花房 宏昭, 南部 静紀, 奥谷 貴弘, 野津 寛大, 粟野 宏之

  (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 193 - 193, Japanese


• 糖原病9a型の3家系6人における食事療法開始後の身長の推移

  池谷 紀衣子, 坊 亮輔, 洪 聖媛, 花房 宏昭, 南部 静紀, 粟野 宏之

  (一社)日本先天代謝異常学会, Oct. 2022, 日本先天代謝異常学会雑誌, 38, 215 - 215, Japanese


• 兵庫県拡大マススクリーニングにおけるムコ多糖症2型の精密検査例の遺伝学的背景の検討

  坊 亮輔, 李 知子, 上田 雅章, 野津 寛大, 竹島 泰弘, 飯島 一誠, 粟野 宏之

  (一社)日本マススクリーニング学会, Aug. 2022, 日本マス・スクリーニング学会誌, 32(2) (2), 233 - 233, Japanese


• 日齢50にonasemnogene abeparvovecを投与した脊髄性筋萎縮症1型の1例

  南部 静紀, 粟野 宏之, 坊 亮輔, 洪 聖媛, 西尾 久英, 飯島 一誠

  (一社)日本小児神経学会, Jul. 2022, 脳と発達, 54(4) (4), 262 - 265, Japanese


• オナセムノゲンアベパルボベク治療後に、ヌシネルセン治療を追加した脊髄性筋萎縮症1型の1例

  南部 静紀, 坊 亮輔, 徳元 翔一, 山口 宏, 冨岡 和美, 西山 将広, 永瀬 裕朗, 西尾 久英, 野津 寛大, 粟野 宏之

  (一社)日本小児神経学会, May 2022, 脳と発達, 54(Suppl.) (Suppl.), S210 - S210, Japanese


• 初回発症時にMASを合併した若年性特発性若年性関節炎の1例

  吉本 啓修, 洪 聖媛, 古林 真佐美, 南部 静紀, 徳元 翔一, 山口 宏, 坊 亮輔, 冨岡 和美, 西山 将広, 粟野 宏之, 永瀬 裕朗, 飯島 一誠

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 545 - 545, Japanese


• 兵庫県における治療可能となった難病に対する拡大新生児マススクリーニングの取り組み

  粟野 宏之, 坊 亮輔, 山本 暢之, 李 知子, 上田 雅章, 野津 寛大, 竹島 泰弘, 飯島 一誠

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 547 - 547, Japanese


• 過去5年間の小児摂食障害に対する家族療法の経験

  冨岡 和美, 永瀬 裕朗, 洪 聖媛, 南部 静紀, 徳元 翔一, 山口 宏, 坊 亮輔, 西山 将広, 粟野 宏之

  (公社)日本小児科学会, Mar. 2022, 日本小児科学会雑誌, 126(3) (3), 551 - 551, Japanese


• Frequent recurrence of pancreatitis in a patient with Leigh syndrome.

  Kengo Nakashima, Ryosuke Bo, Hiroyuki Awano, Masahiro Nishiyama, Kazumoto Iijima

  Jan. 2022, Pediatrics international : official journal of the Japan Pediatric Society, 64(1) (1), e15021, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 極低出生体重児におけるビオチンおよびビオチン関連代謝産物の推移

  坊 亮輔, 山田 健治, 洪 聖媛, 南部 静紀, 藤岡 一路, 小林 弘典, 長谷川 有紀, 渡邊 敏明, 野津 寛大, 粟野 宏之

  (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 131 - 131, Japanese


• 著しい高アンモニア血症がない急性肝障害から診断したOTC欠損症の一例

  洪 聖媛, 南部 静紀, 坊 亮輔, 粟野 宏之

  (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 158 - 158, Japanese


• 尿中有機酸分析がHMG-CoA合成酵素欠損症の発症早期診断に有用であった乳児の一例

  太田 亮, 三星 アカリ, 松本 真明, 永井 正志, 坊 亮輔, 森貞 直哉, 粟野 宏之, 飯島 一誠, 尾崎 佳代

  (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 163 - 163, Japanese


• 極低出生体重児におけるビオチンおよびビオチン関連代謝産物の推移

  坊 亮輔, 山田 健治, 洪 聖媛, 南部 静紀, 藤岡 一路, 小林 弘典, 長谷川 有紀, 渡邊 敏明, 野津 寛大, 粟野 宏之

  (一社)日本先天代謝異常学会, Sep. 2021, 日本先天代謝異常学会雑誌, 37, 131 - 131, Japanese


• The perioperative transition of serum biomarkers of a 1.5-year-old boy with very-long-chain acyl-CoA dehydrogenase deficiency.

  Ryosuke Bo, Hiroyuki Awano, Kenji Yamada, Mayu Ooi, Yuichi Okata, Yuko Bitoh, Satoshi Mizobuchi, Kazumoto Iijima

  Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD, OMIM 201475) is a congenital fatty acid oxidation disorder. Individuals with VLCADD should avoid catabolic states, including strenuous exercise and long-term fasting; however, such conditions are required when undergoing surgery. The perioperative management of VLCADD in infants has rarely been reported and details regarding the transition of serum biomarkers reflecting catabolic status have not been disclosed. Herein, we present the perioperative clinical and biological data of cryptorchidism in a 1.5-year-old boy with VLCADD. The patient was diagnosed through newborn screening and his clinical course was very stable. Genetic testing of ACADVL revealed compound heterozygous variants c.506 T > C (p.Met169Thr) and c.606-609delC (p.L216*). The enzyme activity of the patient with VLCAD was only 20% compared to that of healthy control. Left orchiopexy for the pediatric cryptorchidism was planned and performed at 1 and a half year of age. Induction anesthesia involved thiopental, fentanyl and rocuronium. The glucose infusion rate was maintained above 6.6 mg/kg/min starting the day before surgery until the operation was completed. Anesthesia was maintained with sevoflurane at approximately 2%. The serum concentration of tetradecenoylcarnitine were stable during the operation, ranging between 0.08 and 0.19 μM (cutoff <0.2 μM), and never deviated from the reference range. Concentration of other serum biomarkers including free fatty acid, 3-OH-butyrate, and creatine kinase, remained similarly unchanged. In this report, we describe the uneventful perioperative management of unilateral orchiopexy for left cryptorchidism in a 1.5-year-old boy with VLCADD using sufficient glucose infusion and volatile anesthesia.

  Jun. 2021, Molecular genetics and metabolism reports, 27, 100760 - 100760, English, International magazine

  Link to Kobe Univ. Repository (Kernel)


• ピボキシル基含有抗菌薬内服母体から出生したイソ吉草酸血症の1例

  増田 知佳, 坊 亮輔, 粟野 宏之, 小林 弘典, 但馬 剛, 飯島 一誠

  (一社)日本マススクリーニング学会, May 2021, 日本マス・スクリーニング学会誌, 31(1) (1), 41 - 47, Japanese


• 新生児スクリーニングにおけるシトルリン低値を用いたオルニチントランスカルバミラーゼ(OTC)欠損症スクリーニングの可能性

  李 知子, 坊 亮輔, 粟野 宏之, 上田 雅章, 港 敏則, 竹島 泰弘

  (公社)日本小児科学会, Apr. 2021, 日本小児科学会雑誌, 125(4) (4), 673 - 673, Japanese


• The ACTN3 577XX Null Genotype Is Associated with Low Left Ventricular Dilation-Free Survival Rate in Patients with Duchenne Muscular Dystrophy.

  Masashi Nagai, Hiroyuki Awano, Tetsushi Yamamoto, Ryosuke Bo, Masafumi Matsuo, Kazumoto Iijima

  BACKGROUND: Duchenne muscular dystrophy (DMD) is a fatal progressive muscle-wasting disease caused by mutations in the DMD gene. Dilated cardiomyopathy is the leading cause of death in DMD; therefore, further understanding of this complication is essential to reduce morbidity and mortality. METHODS: A common null variant (R577X) in the ACTN3 gene, which encodes α-actinin-3, has been studied in association with muscle function in healthy individuals; however it has not yet been examined in relationship to the cardiac phenotype in DMD. In this study, we determined the ACTN3 genotype in 163 patients with DMD and examined the correlation between ACTN3 genotypes and echocardiographic findings in 77 of the 163 patients. RESULTS: The genotypes 577RR(RR), 577RX(RX) and 577XX(XX) were identified in 13 (17%), 44 (57%) and 20 (26%) of 77 patients, respectively. We estimated cardiac involvement-free survival rate analyses using Kaplan-Meier curves. Remarkably, the left ventricular dilation (> 55 mm)-free survival rate was significantly lower in patients with the XX null genotype (P < 0.01). The XX null genotype showed a higher risk for LV dilation (hazard ratio 9.04). CONCLUSIONS: This study revealed that the ACTN3 XX null genotype was associated with a lower left ventricular dilation-free survival rate in patients with DMD. These results suggest that the ACTN3 genotype should be determined at the time of diagnosis of DMD to improve patients' cardiac outcomes.

  Oct. 2020, Journal of cardiac failure, 26(10) (10), 841 - 848, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 新生児スクリーニングで経験した興味深い症例提示とその対応 ピボキシル基含有抗生剤内服中の母体より出生したイソ吉草酸血症の一例

  坊 亮輔, 粟野 宏之

  (一社)日本マススクリーニング学会, Sep. 2020, 日本マス・スクリーニング学会誌, 30(2) (2), 135 - 135, Japanese


• False positive cases of elevated tetradecenoyl carnitine in newborn mass screening showed significant loss of body weight.

  Ryosuke Bo, Hiroyuki Awano, Kosuke Nishida, Kazumichi Fujioka, Atsushi Nishiyama, Osamu Miyake, Kazumoto Iijima

  Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency, a condition in which the body is unable to break down long-chain fatty acids properly, is the most common fatty acid oxidation disorder in Japan. Tandem mass spectrometry has been used in newborn screening (NBS), allowing the detection of patients with VLCAD deficiency even before symptoms manifest. However, tandem mass spectrometry has a high false positive rate. We investigated the clinical characteristics of patients with false positive results for tetradecenoyl acylcarnitine (C14:1). This case-control study used data collected between the 1st of January 2014 and the 31st of March 2019. The case group was defined as patients having levels of both C14:1 and C14:1/C2 ratio higher than cut-off levels in the first newborn mass screening, who were eventually diagnosed as false positives by attending doctors at Kobe University Hospital, Palmore Hospital, or Kakogawa Central City Hospital in Japan. The control group comprised 100 patients randomly selected from the three facilities. The false positive group included 17 cases, and the control group contained 300 patients. The demographics of each group did not show any significant differences in sex, body weight at birth, Cesarean section rate, complete breastfeeding rate, or the number of feedings per day. However, the change in body weight at the sampling day of NBS in the false positive and control groups was -10.2%, and - 4.6%, respectively, showing a statistically significant difference (p < 0.01). In addition, body weight gain at the one-month medical checkup was 38.9 g/day in the false positive group and 44.1 g/day in the control group (p < 0.05). An elevation of C14:1 carnitine has been reported in situations involving the catalysis of fatty acid. Therefore, patients with severe body weight loss might be associated with poor sucking or poor milk supply, which might cause a false positive elevation of C14:1 and C14:1/C2. In suspected VLCAD deficiency, attending doctors should pay attention to body weight changes recorded during newborn mass screening.

  Sep. 2020, Molecular genetics and metabolism reports, 24, 100634 - 100634, English, International magazine

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Need for strict clinical management of patients with carnitine palmitoyltransferase II deficiency: Experience with two cases detected by expanded newborn screening.

  Ryosuke Bo, Ikuma Musha, Kenji Yamada, Hironori Kobayashi, Yuki Hasegawa, Hiroyuki Awano, Masato Arao, Toru Kikuchi, Takeshi Taketani, Akira Ohtake, Seiji Yamaguchi, Kazumoto Iijima

  In Japan, carnitine palmitoyltransferase II (CPTII) deficiency has been included as one of the primary target diseases in the expanded newborn mass screening program since 2018. However, many cases of the severe infantile hepatocardiomuscular form of CPTII deficiency showed severe neurodevelopmental delay or sudden death, which indicated that management of CPTII deficiency in the acute phase remains to be studied in detail. Herein, we discuss two cases diagnosed by newborn mass screening. Patient 1 was under strict clinical management from the neonatal period, with >20 admissions in 14 months, while Patient 2 was managed using a relatively relaxed approach, with only 2 admissions in the same period. Patient 1 showed normal development; however, Patient 2 expired at the age of 1 year 2 months. To develop strategies for preventing sudden deaths in patients with CPTII deficiency, this retrospective study focused on detailed clinical management practices and biochemical findings during the acute phase. We also investigated the correlation between conventional biomarkers (such as creatine kinase) and long-chain acylcarnitines. We propose that strict monitoring and immediate medical attention, even in case of slight fever or minor abdominal symptoms, can help prevent sudden death in patients with CPTII deficiency. Considering the higher morbidity rate of such patients, strict and acute management of CPTII deficiency cannot be overemphasized.

  Sep. 2020, Molecular genetics and metabolism reports, 24, 100611 - 100611, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• ACTN3ヌル遺伝子型はDMDの拡張型心筋症の早期発症と関連する

  永井 正志, 粟野 宏之, 山本 哲志, 坊 亮輔, 西尾 久英, 松尾 雅文, 飯島 一誠

  (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S248 - S248, Japanese


• 神経筋疾患患者に対する排痰補助装置のオシレーション機能が及ぼす気道分泌物除去効果に関する検討

  粟野 宏之, 永井 正志, 坊 亮輔, 石田 悠介, 冨岡 和美, 西山 将広, 竹田 洋樹, 永瀬 裕朗, 飯島 一誠

  (一社)日本小児神経学会, Aug. 2020, 脳と発達, 52(Suppl.) (Suppl.), S300 - S300, Japanese


• CPT2欠損症では厳格な入院管理体制が必要である

  坊 亮輔, 山田 健治, 武者 育麻, 小林 弘典, 長谷川 有紀, 粟野 宏之, 大竹 明, 山口 清次

  (株)メディカルレビュー社, Apr. 2020, The Lipid, 31(1) (1), 91 - 91, Japanese


• 抗アセチルコリン受容体抗体価が発症時0.3nmol/Lから最大15.4nmol/Lに上昇した眼筋型重症筋無力症

  洪 聖媛, 西山 将広, 田中 司, 永井 正志, 坊 亮輔, 石田 悠介, 冨岡 和美, 粟野 宏之, 永瀬 裕朗, 飯島 一誠

  (株)日本小児医事出版社, Apr. 2020, 小児科臨床, 73(4) (4), 499 - 502, Japanese


• 胃腸炎回復期に低血糖を起こした中鎖アシルCoA脱水素酵素(MCAD)欠損症の一例

  中西 啓太, 邱 智前, 呉 東祐, 小谷 晋平, 鴨井 良明, 金 修妍, 山根 正之, 奥谷 貴弘, 坊 亮輔, 粟野 宏之, 飯島 一誠

  (公社)日本小児科学会, Feb. 2020, 日本小児科学会雑誌, 124(2) (2), 405 - 405, Japanese


• 乳汁分泌不全による栄養障害性脂肪肝

  吉田 阿寿美, 石森 真吾, 坊 亮輔, 阪田 美穂, 粟野 宏之, 親里 嘉展, 西山 敦史, 米谷 昌彦

  生後10ヵ月、女児。生後8ヵ月までは体重増加、運動発達も問題はなかったが、同時期に母親が妊娠6週目であることが発覚し、以後、母親の乳汁分泌の低下に伴い、児は急激な体重減少や、つかまり立ちができなくなると言った退行が認められ、精査目的で当院へ受診となった。入院時、肝逸脱酵素の上昇、脂肪肝、血糖低下、血中乳酸値上昇を認め、先天性代謝異常症が疑われたが、経管栄養により体重は増加し、退行していた各症状も改善した。以上、これらの臨床的経過から、本症例の原因は最終的に乳汁分泌不全による栄養障害性脂肪肝と診断された。

  (公社)日本小児科学会, Dec. 2019, 日本小児科学会雑誌, 123(12) (12), 1812 - 1818, Japanese


• 兵庫県内の1型糖尿病患者に対するグルカゴン製剤の処方率

  松本 真明, 廣田 勇士, 永井 正志, 坊 亮輔, 松岡 敦子, 浜口 哲矢, 竹内 健人, 中川 靖, 粟野 宏之

  日本先進糖尿病治療研究会, Nov. 2019, 日本先進糖尿病治療研究会雑誌, 15, 46 - 46, Japanese


• 新生児マススクリーニングにおけるC14:1偽陽性例では出生後の体重減少が大きい

  坊 亮輔, 粟野 宏之, 西田 浩輔, 藤岡 一路, 西山 敦史, 三宅 理, 飯島 一誠

  日本マススクリーニング学会, Oct. 2019, 日本マス・スクリーニング学会誌, 29(2) (2), 190 - 190, Japanese

  [Refereed]


• Preliminary Effectiveness and Safety of High Frequency Oscillation in Addition to Mechanical Insufflation and Exsufflation for Intratracheal Mucus Removal in Patients With Neuromuscular Disease: Protocol for a Prospective Study.

  Awano H, Nagai M, Bo R, Murao M, Ishida Y, Tanaka T, Tomioka K, Nishiyama M, Nagase H, Iijima K

  BACKGROUND: Mechanical insufflation-exsufflation (MI-E) is necessary for noninvasive management of respiratory clearance in patients with neuromuscular disorders (NMDs). Its utility has been proven, and the technique is recommended in a number of international guidelines for the management of patients with NMDs. However, the clearance of thick secretions adhering to the tracheobronchial walls could be problematic when these patients suffer from respiratory tract infections. To improve the effectiveness of the noninvasive technique, a novel device combining MI-E with high frequency oscillation (HFO) has been developed. However, the efficacy of HFO therapy in NMDs has not been well studied. OBJECTIVE: The aim of this study was to elucidate the effect of MI-E combined with HFO for mucus removal in NMD patients. To evaluate its efficacy, changes in transcutaneous oxygen saturation (SpO2), which may predict intratracheal mucus removal, will be measured before and after use of MI-E. METHODS: This is a single-center, nonblinded, nonrandomized prospective study that will enroll 5 subjects hospitalized in Kobe University Hospital owing to respiratory tract infection. All subjects will receive MI-E therapy a few times daily and will receive HFO every other day, for 6 days. Before and after MI-E use, SpO2 will be obtained and the change in SpO2 (ΔSpO2) between MI-E with and without HFO will be calculated. For every subject, the average of ΔSpO2 with or without HFO will be obtained and the null hypothesis that there is a mean change of 0 in the SpO2 between MI-E with and without HFO will be tested using the paired t test. If the treatment with HFO is found to be statistically significantly superior to the treatment without HFO, the study will conclude that HFO addition is more efficacious than no HFO addition. RESULTS: A total of 2 subjects have already been recruited and enrolled in this study as of August 2018. CONCLUSIONS: This unique protocol will assess the efficacy of adding HFO to MI-E during the acute phase of respiratory tract infection in patients with NMDs. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/12102.

  Jun. 2019, JMIR research protocols, 8(6) (6), e12102, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Duchenne型筋ジストロフィー患者を対象としたわさびの根茎に含まれるスルフィニル成分の筋崩壊抑制効果の検討

  粟野 宏之, 永井 正志, 坊 亮輔, 松本 真明, 白川 卓, 丸山 順裕, 鍋島 陽一, 松尾 雅文, 飯島 一誠

  (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S264 - S264, Japanese


• The prescription rates of glucagon for hypoglycemia by pediatricians and physicians are low in Japan.

  Masaaki Matsumoto, Hiroyuki Awano, Yushi Hirota, Masashi Nagai, Ryosuke Bo, Atsuko Matsuoka, Tetsushi Hamaguchi, Takehito Takeuchi, Yasushi Nakagawa, Wataru Ogawa, Kazumoto Iijima

  PURPOSE: Hypoglycemia is a common and life-threatening complication in type 1 diabetes mellitus (T1DM) patients. Current guidelines recommend glucagon for treating hypoglycemia in out-of-hospital settings; however, glucagon is reportedly underused in such patients. We conducted a doctor-oriented, questionnaire-based survey of pediatricians and physicians to determine the glucagon prescription rate and identify the reason(s) for its underuse in T1DM patients. METHODS: A questionnaire was mailed to 415 pediatricians and 200 physicians employed at 66 facilities with >100 general wards throughout Hyogo, Japan. The following variables were surveyed: doctor's specialty, glucagon prescription rate, familiarity with glucagon use guidelines, barriers to prescribing glucagon, and attitude changes after education. RESULTS: After 16 doctors were found to have retired, 599 doctors were enrolled; 305 (187 pediatricians and 118 physicians) returned a completed questionnaire. In all, 45 pediatricians and 104 physicians were treating T1DM patients, of whom 24% and 28% reported prescribing glucagon, respectively. The guideline familiarity rate among pediatricians was lower than that among physicians. The major barrier to prescribing glucagon was the complex preparation procedure required by patients/caregivers. More than half of the doctors who did not prescribe glucagon began doing so after being educated about the guidelines. CONCLUSION: The glucagon prescription rate was low among both pediatricians and physicians in Japan.

  May 2019, Endocrine, 64(2) (2), 233 - 238, English, International magazine

  [Refereed]

  Link to Kobe Univ. Repository (Kernel)


• 兵庫県内の糖尿病内科医の1型糖尿病患者に対するグルカゴン製剤の処方実態

  中川 靖, 廣田 勇士, 松本 真明, 浜口 哲矢, 松岡 敦子, 竹内 健人, 永井 正志, 坊 亮輔, 粟野 宏之, 小川 渉

  (一社)日本糖尿病学会, Apr. 2019, 糖尿病, 62(4) (4), 257 - 257, Japanese


• FreeStyle Libreの1型糖尿病患者での測定精度に関する検討

  松本 真明, 高橋 利和, 永井 正志, 坊 亮輔, 粟野 宏之, 中川 靖, 廣田 勇士, 小川 渉, 飯島 一誠

  日本先進糖尿病治療研究会, Nov. 2018, 日本先進糖尿病治療研究会雑誌, 14, 39 - 39, Japanese


• タンデムマス法による新生児マススクリーニング検査により早期診断した原発性全身性カルニチン欠乏症の乳児例

  芳原 良子, 糸永 知代, 関口 和人, 前田 美和子, 福島 直喜, 山口 清次, 坊 亮輔, 笹井 英雄, 深尾 敏幸, 井原 健二

  症例は3ヵ月女児で、日齢4に施行したタンデムマス法による新生児マススクリーニング検査で遊離カルニチン(C0)低値を指摘されていた。その後も肝逸脱酵素上昇なども認めたため、精査目的で当院小児科に入院した。C0低値、他のアシルカルニチン低値、カルニチンクリアランス上昇、母親C0正常でカルニチンクリアランス正常、肝逸脱酵素上昇、腹部エコー検査で脂肪肝の所見を認め、原発性全身性カルニチン欠乏症と臨床診断した。速やかにレボカルニチンの補充療法を開始した。徐々に肝逸脱酵素は低下し、生後1歳の時点で基準値内となった。感染症罹患、特に胃腸炎罹患の際には低血糖の危険性があり、入院の上で経口摂取が回復するまで糖液補液治療を2度行ったが、急性発症することはなかった。2歳5ヵ月現在、発達と発育は正常である。

  (一社)大分市医師会, Jun. 2018, アルメイダ医報, 43(1) (1), 55 - 59, Japanese


• Renal insufficiency mimicking glutaric acidemia type 1 on newborn screening

  Matsumoto Masaaki, Awano Hiroyuki, Bo Ryosuke, Nagai Masashi, Tomioka Kazumi, Nishiyama Masahiro, Ninchouji Takeshi, Nagase Hiroaki, Yagi Mariko, Morioka Ichiro, Hasegawa Yuki, Takeshima Yasuhiro, Iijima Kazumoto

  Jan. 2018, Pediatrics International (Web), 60(1) (1), 67‐69, English

  [Refereed]

  Scientific journal


• Renal insufficiency mimicking glutaric acidemia type 1 on newborn screening.

  Matsumoto M, Awano H, Bo R, Nagai M, Tomioka K, Nishiyama M, Ninchouji T, Nagase H, Yagi M, Morioka I, Hasegawa Y, Takeshima Y, Iijima K

  BACKGROUND: Glutaryl carnitine (C5DC) in dried blood spots is used as a biomarker for glutaric aciduria type 1 (GA-1) screening. C5DC, however, is the only screening marker for this condition, and various pathological conditions may interfere with C5DC metabolism. Recently, C5DC elevation has been reported in cases of renal insufficiency. METHOD: Five patients who were positive for GA-1 on newborn screening with tandem mass spectrometry between September 2012 and March 2015 at Kobe University Hospital were enrolled in this study. RESULTS: GA-1 was not confirmed on urinary organic acids analysis in any of the patients. C5DC decreased immediately in four patients, but one patient, who had high C5DC for at least 4 months, was diagnosed with bilateral renal hypoplasia. CONCLUSION: In the case of persistently elevated C5DC, renal insufficiency should be considered as a differential diagnosis.

  Jan. 2018, Pediatrics international : official journal of the Japan Pediatric Society, 60(1) (1), 67 - 69, English, International magazine

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• Newborn screening for carnitine palmitoyltransferase II deficiency using (C16+C18:1)/C2: Evaluation of additional indices for adequate sensitivity and lower false-positivity

  Go Tajima, Keiichi Hara, Miyuki Tsumura, Reiko Kagawa, Satoshi Okada, Nobuo Sakura, Shinsuke Maruyama, Atsuko Noguchi, Tomonari Awaya, Mika Ishige, Nobuyuki Ishige, Ikuma Musha, Sayaka Ajihara, Akira Ohtake, Etsuo Naito, Yusuke Hamada, Tomotaka Kono, Tomoko Asada, Hideo Sasai, Toshiyuki Fukao, Ryoji Fujiki, Osamu Ohara, Ryosuke Bo, Kenji Yamada, Hironori Kobayashi, Yuki Hasegawa, Seiji Yamaguchi, Masaki Takayanagi, Ikue Hata, Yosuke Shigematsu, Masao Kobayashi

  Nov. 2017, MOLECULAR GENETICS AND METABOLISM, 122(3) (3), 67 - 75, English

  [Refereed]

  Scientific journal


• Clinical and molecular investigation of 14 Japanese patients with complete TFP deficiency: a comparison with Caucasian cases

  Ryosuke Bo, Kenji Yamada, Hironori Kobayashi, Purevsuren Jamiyan, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Ikue Hata, Yo Niida, Yosuke Shigematsu, Kazumoto Iijima, Seiji Yamaguchi

  Sep. 2017, JOURNAL OF HUMAN GENETICS, 62(9) (9), 809 - 814, English

  [Refereed]

  Scientific journal


• A newborn case with carnitine palmitoyltransferase II deficiency initially judged as unaffected by acylcarnitine analysis soon after birth

  Kenji Yamada, Ryosuke Bo, Hironori Kobayashi, Yuki Hasegawa, Mako Ago, Seiji Fukuda, Seiji Yamaguchi, Takeshi Taketani

  Elsevier Inc., Jun. 2017, Molecular Genetics and Metabolism Reports, 11, 59 - 61, English

  [Refereed]

  Scientific journal

  Link to Kobe Univ. Repository (Kernel)


• 乳幼児期における発達障害児の感覚特性についての検討 自閉症および知的障害特性との関連

  前山 花織, 高木 康子, 吉岡 三惠子, 加藤 威, 溝渕 雅巳, 北山 真次, 高田 哲, 坊 亮輔, 冨岡 和美, 西山 将広, 粟野 宏之, 永瀬 裕朗, 飯島 一誠, 西村 範行

  (一社)日本小児神経学会, May 2017, 脳と発達, 49(Suppl.) (Suppl.), S360 - S360, Japanese


• 幼児期からの糖・脂質代謝の経過をフォローしえたPTRF遺伝子変異による全身性脂肪萎縮症の一例

  松本 真明, 粟野 宏之, 廣田 勇士, 永井 正志, 坊 亮輔, 冨岡 和美, 前山 花織, 西山 将広, 李 知子, 永瀬 裕明, 八木 麻理子, 竹島 泰弘, 小川 渉, 飯島 一誠

  (一社)日本糖尿病学会, Apr. 2017, 糖尿病, 60(Suppl.1) (Suppl.1), S - 379, Japanese


• Efficacy and Complications of Fosphenytoin Versus Continuous Midazolam in Children with Febrile Status Epilepticus

  NISHIYAMA Masahiro, NAGASE Hiroaki, ISHIDA Yusuke, TANAKA Tsukasa, FUJITA Kyoko, TOYOSHIMA Daisaku, MARUYAMA Azusa, MATSUMOTO Masaaki, TOMIOKA Kazumi, BO Ryosuke, MAEYAMA Kaori, AWANO Hiroyuki, TAKEDA Hiroki, UETANI Yoshiyuki, TAKADA Satoshi, IIJIMA Kazumoto

  Apr. 2017, Brain & Development, 39(3 Supplement) (3 Supplement), 330, English

  [Refereed]

  Scientific journal


• 超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討

  松本 真明, 粟野 宏之, 永井 正志, 坊 亮輔, 冨岡 和美, 前山 花織, 西山 将広, 永瀬 裕朗, 森岡 一朗, 飯島 一誠

  (公社)日本小児科学会, Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 374 - 374, Japanese


• Efficacy of bezafibrate on fibroblasts of glutaric acidemia type II patients evaluated using an in vitro probe acylcarnitine assay

  Kenji Yamada, Hironori Kobayashi, Ryosuke Bo, Jamiyan Purevsuren, Yuichi Mushimoto, Tomoo Takahashi, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Seiji Yamaguchi

  Jan. 2017, BRAIN & DEVELOPMENT, 39(1) (1), 48 - 57, English

  [Refereed]

  Scientific journal


• A de novo 50-bp GNAS Intragenic Duplication in a Patient with Pseudohypoparathyroidism Type 1a.

  Erina Suzuki, Ryosuke Bo, Kaori Sue, Hiroyuki Awano, Tsutomu Ogata, Satoshi Narumi, Masayo Kagami, Shinichiro Sano, Maki Fukami

  Germline intragenic mutations in the GNAS locus result in pseudohypoparathyroidism type 1a (PHP1a) and related conditions. Nearly half of the previously reported GNAS intragenic mutations were structural variants, including 3 tandem duplications of 12-25 bp. However, the precise mutation spectrum and the genomic basis of GNAS structural variants remain to be clarified. Here, we report a de novo 50-bp tandem duplication in GNAS (c.723_772dup50, p.Glu259Leufs*29) identified in a patient with typical clinical features of PHP1a. The mutant transcript was predicted to undergo mRNA decay or encode a nonfunctional protein. The 2 breakpoints of the duplication shared a 1-bp microhomology but were not associated with long homology or nucleotide stretches. We also examined the breakpoint structures of 3 previously reported GNAS duplications and found that 1 had a structure similar to that of our case, while the remaining 2 had blunt-ended breakpoints without microhomologies. In silico analyses revealed that the GNAS-flanking region was not enriched with repeats, palindromes, noncanonical DNA motifs, or GC content. This study expands the mutation spectrum of GNAS and provides the first indication that GNAS intragenic structural variants are induced by multiple processes, including nonhomologous end-joining and/or microhomology-mediated break-induced replication, independently of known rearrangement-inducing DNA features.

  2017, Cytogenetic and genome research, 153(3) (3), 125 - 130, English, International magazine

  [Refereed]

  Scientific journal


• 頻回の入院管理によって代謝不全を予防したカルニチンパルミトイルトランスフェラーゼ(CPT)-2欠損症の1例

  BOU RYOUSUKE

  Nov. 2016, 特殊ミルク情報, (52) (52), 48 - 51, Japanese

  Scientific journal


• LC-MS/MSによる血清中アシルカルニチンの定量分析の新規非誘導体化法の開発及び既存簡易測定法との比較検討

  小林 弘典, 山田 健治, 坊 亮輔, 長谷川 有紀, 山口 清次, 大山 直子, 竹内 一博, 城下 友義, 井手野 晃

  (一社)日本医用マススペクトル学会, Aug. 2016, JSBMS Letters, 41(Suppl.) (Suppl.), 50 - 50, Japanese


• Clinical, biochemical and molecular investigation of adult-onset glutaric acidemia type II: Characteristics in comparison with pediatric cases

  Kenji Yamada, Hironori Kobayashi, Ryosuke Bo, Tomoo Takahashi, Jamiyan Purevsuren, Yuki Hasegawa, Takeshi Taketani, Seiji Fukuda, Takuya Ohkubo, Takanori Yokota, Mutsufusa Watanabe, Taiji Tsunemi, Hidehiro Mizusawa, Hiroshi Takuma, Ayako Shioya, Akiko Ishii, Akira Tamaoka, Yosuke Shigematsu, Hideo Sugie, Seiji Yamaguchi

  Mar. 2016, BRAIN & DEVELOPMENT, 38(3) (3), 293 - 301, English

  [Refereed]

  Scientific journal


• インフルエンザ罹患を機に意識障害を呈し、ミトコンドリアHMG-CoA合成酵素欠損症と診断した1例

  李 知子, 濱平 陽史, 坊 亮輔, 山田 健治, 小林 弘典, 長谷川 有紀, 山口 清次, 笹井 英雄, 大塚 博樹, 深尾 敏幸, 飯島 一誠, 竹島 泰弘

  (公社)日本小児科学会, Jan. 2016, 日本小児科学会雑誌, 120(1) (1), 91 - 91, Japanese


• Metabolic Survey of Hidden Inherited Metabolic Diseases in Children With Apparent Life-Threatening Event(ALTE)or Sudden Unexpected Death in Infancy(SUDI)by Analyses of Organic Acids and Acylcarnitines Using Mass Spectrometries

  Takahashi Tomoo, Hasegawa Yuki, Yamada Kenji, Bo Ryosuke, Kobayashi Hironori, Taketani Takeshi, Fukuda Seiji, Yamaguchi Seiji

  To determine the relation between sudden unexpected death in infancy （SUDI） or apparent lifethreatening events （ALTE） and inborn errors of metabolism （IMD）, we investigated clinical and biochemical features in patients presenting with SUDI or ALTE, who were diagnosed with having hidden IMD. Subjects were infants between aged from 2 days and 3 years, detected during the period b

  Shimane University Faculty of Medicine, 2016, Shimane journal of medical science, 32(2) (2), 61 - 68, English

  [Refereed]

  Scientific journal


• Elevation of pivaloylcarnitine by sivelestat sodium in two children.

  Kenji Yamada, Hironori Kobayashi, Ryosuke Bo, Tomoo Takahashi, Yuki Hasegawa, Makoto Nakamura, Nobuyuki Ishige, Seiji Yamaguchi

  Nov. 2015, Molecular genetics and metabolism, 116(3) (3), 192 - 4, English, International magazine

  [Refereed]

  Scientific journal


• A fetus with mitochondrial trifunctional protein deficiency: Elevation of 3-OH-acylcarnitines in amniotic fluid functionally assured the genetic diagnosis.

  BO RYOSUKE

  Mitochondrial trifunctional protein (TFP) is a multienzyme complex that catalyzes the last three steps of the β-oxidation cycle of long-chain fatty acids. In the prenatal diagnosis of TFP deficiency, acylcarnitine (AC) analysis has been considered difficult because of limited excretion of long-chain ACs into the fetal urine and hence into the amniotic fluid. Here, we report our

  Nov. 2015, Mol Genet Metab Rep., 5(6) (6), 1 - 4, English

  [Refereed]

  Scientific journal


• 臨床検査を目的としたLC-MS/MSによる血清中アシルカルニチンの定量分析法の開発

  小林 弘典, 山田 健治, 坊 亮輔, 長谷川 有紀, 山口 清次, 城下 友義, 伊藤 利将, 井手野 晃, 大原 利成

  (一社)日本医用マススペクトル学会, Aug. 2015, JSBMS Letters, 40(Suppl.) (Suppl.), 78 - 78, Japanese

• 神経学的症状の精査の中で診断に至った偽性副甲状腺機能低下症の3症例

  朝貝芳貴, 花房宏昭, 大橋浩基, 池谷紀衣子, 曽根原晶子, 洪聖媛, 坊亮輔, 永瀬裕朗, 野津寛大

  2025, 近畿小児科学会プログラム・抄録集, 38th


• 便中のフィルムアレイ検査が診療方針決定に有用であったエルシニア腸炎の2例

  酒井菜々花, 朝貝芳貴, 大橋浩基, 末宗和樹, 斉賀佳穂, 曽根原晶子, 鮫島智大, 花房宏昭, 老川静香, 南部静紀, 徳元翔一, 山口宏, 坊亮輔, 永瀬裕朗, 野津寛大

  2025, 日本小児科学会雑誌, 129(6) (6)


• 摂食障害患者の体重の回復と骨密度の検討

  伊藤立人, 冨岡和美, 川村葵, 曽根原晶子, 京野由紀, 鮫島智大, 花房宏昭, 老川静香, 南部静紀, 徳元翔一, 山口宏, 坊亮輔, 野津寛大, 永瀬裕朗

  2025, 日本小児科学会雑誌, 129(6) (6)


• 幅広い血縁者の解析がバリアントの評価に有用であったARXによる発達性てんかん性脳症の1男児例

  花房宏昭, 花房宏昭, 山口宏, 澤田優貴, 田中敬子, 老川静香, 坊亮輔, 中川卓, 森貞直哉, 野津寛大, 永瀬裕朗

  2025, 日本小児遺伝学会学術集会プログラム・抄録集, 47th


• 血清アシルカルニチン分析で異常を認めない横紋筋融解症に対して網羅的遺伝子解析が有用であった3例

  曽根原晶子, 坊亮輔, 朝貝芳貴, 大橋浩基, 池谷紀衣子, 花房宏昭, 南部静紀, 森貞直哉, 粟野宏之, 野津寛大

  2025, 近畿小児科学会プログラム・抄録集, 38th


• MCAD欠損症8名のsick day時の臨床データおよび注意点

  大橋浩基, 坊亮輔, 朝貝芳貴, 曽根原晶子, 池谷紀衣子, 金谷真吾, 花房宏昭, 南部静紀, 山本寛子, 西山敦史, 奥谷貴弘, 尾崎佳代, 粟野宏之, 野津寛大

  2025, 近畿小児科学会プログラム・抄録集, 38th


• Examination of the rate of consent obtained for expanded newborn screening at our hospital

  山本寛子, 徳田央士, 松野下夏樹, 竹中佳奈栄, 富永健太, 川崎圭一郎, 坊亮輔, 山本暢之, 野津寛大, 李知子, 竹島泰弘

  2025, 日本小児科学会雑誌, 129(2) (2)


• The second case of a child with systemic carnitine deficiency, in which multiple institutions worked together before birth to safely manage the perinatal period before genetic results were available

  尾崎佳代, 西藤知城, 柏坂舞, 池谷紀衣子, 松本真明, 坊亮輔, 山本茜, 小林弘典, 森貞直哉

  2024, 日本マススクリーニング学会誌, 34(2) (2)


• The impact of the rise in cost of the expanded newborn screening on the number of tests and the rate of consent obtained

  大橋浩基, 坊亮輔, 曽根原晶子, 洪聖媛, 花房宏昭, 南部静紀, 藤岡一路, 粟野宏之, 野津寛大

  2024, 日本小児科学会雑誌, 128(2) (2)


• 兵庫県内の糖尿病内分泌内科医を対象とした経鼻グルカゴン製剤に対するアンケート調査

  高吉倫史, 廣田勇士, 松本真明, 池谷紀衣子, 池谷紀衣子, 曽根原晶子, 上田真莉子, 西影星二, 芳村魁, 山本あかね, 坊亮輔, 粟野宏之

  2024, 糖尿病(Web), 67(2) (2)


• 古典型フェニルケトン尿症に対しペグバリアーゼを導入することによりフェニルアラニン血中濃度を低下することができた一例

  酒井善紀, 坊亮輔, 角谷美咲, 橋本七月, 池谷紀衣子, 曽根原晶子, 花房宏昭, 南部静紀, 粟野宏之

  2024, 兵庫県小児科医会報, (82) (82)


• A newborn case of congenital lactose intolerance (CLD) detected by newborn mass screening (NBS)

  大橋浩基, 朝貝芳貴, 曽根原晶子, 花房宏昭, 南部静紀, 粟野宏之, 坊亮輔

  2024, 日本マススクリーニング学会誌, 34(2) (2)


• 乳酸/ピルビン酸比の上昇を伴う高乳酸血症を呈したフルクトース1,6ビスホスファターゼ欠損症の新生児例

  内藤沙苗, 坊亮輔, 池谷紀衣子, 大橋浩基, 曽根原晶子, 花房宏昭, 南部静紀, 福嶋祥代, 五百蔵智明, 粟野宏之

  2024, 日本先天代謝異常学会雑誌, 40 (CD-ROM)


• MCAD欠損症8名のシックデイ時の臨床データおよび注意点

  大橋浩基, 曽根原晶子, 池谷紀衣子, 南部静紀, 金谷真吾, 山本寛子, 西山敦史, 尾崎佳代, 粟野宏之, 坊亮輔

  2024, 日本先天代謝異常学会雑誌, 40 (CD-ROM)


• シトルリン低値による遅発型オルニチントランスカルバミラーゼ(OTC)欠損症・カルバミルリン酸合成酵素(CPS)1欠損症に対する新生児スクリーニング~兵庫県でのpilot study~

  李知子, 上田雅章, 坊亮輔, 粟野宏之, 竹島泰弘

  2024, 日本小児科学会雑誌, 128(4) (4)


• 兵庫県拡大新生児スクリーニングで発見された脊髄性筋萎縮症の3例

  曽根原晶子, 坊亮輔, 池谷紀衣子, 南部静紀, 山本暢之, 李知子, 上田剛, 上田雅章, 奥谷貴弘, 菅原勝美, 粟野宏之, 竹島泰弘, 飯島一誠, 野津寛大

  2024, 日本小児科学会雑誌, 128(4) (4)


• 兵庫県における拡大新生児マススクリーニングの現状

  武田紗季, 李知子, 柴田暁男, 坊亮輔, 山本暢之, 上田雅章, 粟野宏之, 野津寛大, 飯島一誠, 竹島泰弘

  2024, 日本周産期・新生児医学会雑誌(Web), 60(Suppl.1) (Suppl.1)


• 拡大新生児マススクリーニングでムコ多糖症1型と診断したが心筋症を呈し造血幹細胞移植に難航している1例

  曽根原晶子, 坊亮輔, 久保慎吾, 佐藤有美, 山本暢之, 山本将平, 李知子, 粟野宏之, 竹島泰弘, 野津寛大

  2024, 日本先天代謝異常学会雑誌, 40 (CD-ROM)


• 医師を対象とした非医療従事者による経鼻グルカゴン製剤使用に関する意見調査

  松本真明, 池谷紀衣子, 曽根原晶子, 高吉倫史, 山本あかね, 上田真莉子, 坊亮輔, 廣田勇士, 小川渉, 粟野宏之

  2023, 日本小児・思春期糖尿病学会年次学術集会プログラム・抄録集, 28th


• 神戸こども初期急病センターを受診した低血糖患者における“血清グルコース値×Δanion gap”の分布

  洪聖媛, 坊亮輔, 曽根原晶子, 近藤淳, 花房宏昭, 鮫島智大, 南部静紀, 野津寛大, 粟野宏之, 粟野宏之

  2023, 日本先天代謝異常学会雑誌, 39


• High expectancy of nasal glucagon administration by non-healthcare professionals among pediatricians

  松本真明, 池谷紀衣子, 池谷紀衣子, 曽根原晶子, HONG Sungwon, 樋口アカリ, 高吉倫史, 山本茜, 西影星二, 芳村魁, 上田真莉子, 坊亮輔, 尾崎佳代, 廣田勇士, 粟野宏之

  2023, 日本小児内分泌学会学術集会プログラム・抄録集, 56th


• SMAの新生児マススクリーニング:ヘパリン加血液で作成した乾燥濾紙血検体を用いたPCR検査の検討

  吉田奈津希, 野口依子, 籔内温子, 松本久幸, 今西孝充, 矢野嘉彦, 坊亮輔, 粟野宏之, 西尾久英

  2023, 日本臨床検査医学会誌, 71


• 遺伝学的検査が死後の原因検索に有用であったグルタル酸血症2型の症例

  花房宏昭, 花房宏昭, 坊亮輔, 坊亮輔, 曽根原晶子, 洪聖媛, 南部静紀, 平久進也, 森貞直哉, 粟野宏之, 野津寛大, 野津寛大

  2023, 日本小児遺伝学会学術集会プログラム・抄録集, 46th


• 兵庫県内の1型糖尿病患者に対する経鼻グルカゴン製剤の処方の実態

  松本真明, 池谷紀衣子, 池谷紀衣子, 曽根原晶子, 洪聖媛, 樋口アカリ, 高吉倫史, 山本あかね, 西影星二, 芳村魁, 上田真莉子, 坊亮輔, 尾崎佳代, 廣田勇士, 小川渉, 粟野宏之

  2023, 日本先進糖尿病治療研究会雑誌(Web), 17(3) (3)


• A SMA1 infant who received Zolgensma therapy at the age of 50 days

  南部静紀, 粟野宏之, 洪聖媛, 徳元翔一, 山口宏, 坊亮輔, 冨岡和美, 西山将広, 篠原正和, 永瀬裕朗, 西尾久英, 飯島一誠

  2021, 日本小児科学会雑誌, 125(2) (2)


• 胃腸炎罹患後に低血糖発作をおこした中鎖アシルCoA脱水素酵素(MCAD)欠損症の1例

  坊亮輔, 粟野宏之, 永井正志, 中西啓太, 石田悠介, 冨岡和美, 村尾真理子, 田中司, 西山将広, 奥谷貴弘, 永瀬裕朗, 飯島一誠

  2020, 日本小児科学会雑誌, 124(6) (6)


• 治療抵抗性の眼筋型重症筋無力症に対してステロイドパルス療法を行った2歳女児例

  洪聖媛, 田中司, 西山将広, 永井正志, 坊亮輔, 石田悠介, 冨岡和美, 村尾真理子, 粟野宏之, 永瀬裕朗, 飯島一誠

  2020, 日本小児科学会雑誌, 124(6) (6)


• 1歳以降にヌシネルセン治療を開始した脊髄性筋萎縮症1型の3例

  永井 正志, 粟野 宏之, 坊 亮輔, 村尾 真理子, 石田 悠介, 冨岡 和美, 田中 司, 西山 将広, 永瀬 裕朗, 西尾 久英, 飯島 一誠

  (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S288 - S288, Japanese


• 1歳以降にヌシネルセン治療を開始した脊髄性筋萎縮症1型の3例

  永井 正志, 粟野 宏之, 坊 亮輔, 村尾 真理子, 石田 悠介, 冨岡 和美, 田中 司, 西山 将広, 永瀬 裕朗, 西尾 久英, 飯島 一誠

  (一社)日本小児神経学会, May 2019, 脳と発達, 51(Suppl.) (Suppl.), S288 - S288, Japanese


• 酵素活性・負荷試験で異常を認めなかった糖原病IXa型の2歳男児例

  坊 亮輔, 粟野 宏之, 元生 和宏, 永井 正志, 松本 真明, 冨岡 和美, 前山 花織, 田中 司, 西山 将広, 中尻 智史, 西山 敦史, 永瀬 裕朗, 飯島 一誠

  (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 615 - 615, Japanese


• 新生児マススクリーニングを契機に発見された先天性乳糖不耐症の新生児例

  坊 亮輔, 粟野 宏之, 永井 正志, 松本 真明, 冨岡 和美, 田中 司, 西山 将広, 永瀬 裕朗, 飯島 一誠

  (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 623 - 623, Japanese


• 1型糖尿病患者に対するグルカゴンの処方実態

  松本 真明, 粟野 宏之, 廣田 勇士, 永井 正志, 坊 亮輔, 冨岡 和美, 前山 花織, 田中 司, 西山 将広, 永瀬 裕朗, 小川 渉, 飯島 一誠

  (公社)日本小児科学会, Mar. 2019, 日本小児科学会雑誌, 123(3) (3), 616 - 616, Japanese


• バセドウ病を合併した若年ミオクロニーてんかんの1例

  三上華奈, 永井正志, 石田悠介, 冨岡和美, 村尾真理子, 田中司, 坊亮輔, 西山将広, 粟野宏之, 永瀬裕朗, 竹中佳奈栄, 飯島一誠

  2019, 日本小児科学会雑誌, 123(3) (3)


• 幼児期からヌシネルセン治療を開始した脊髄性筋萎縮症3型の2例の経過

  永井正志, 粟野宏之, 坊亮輔, 村尾真理子, 石田悠介, 冨岡和美, 田中司, 西山将広, 永瀬裕朗, 西尾久英, 飯島一誠

  2019, 日本小児科学会雑誌, 123(2) (2)


• 急性散在性脳脊髄炎の髄液所見の検討

  西山将広, 永井正志, 坊亮輔, 冨岡和美, 前山花織, 田中司, 粟野宏之, 永瀬裕朗, 佐々木香織, 親里嘉展, 中川卓, 高見勇一, 山口宏, 山口宏, 石田悠介, 石田悠介, 豊嶋大作, 丸山あずさ, 飯島一誠

  2019, 日本小児科学会雑誌, 123(3) (3)


• 7歳時に診断した若年/成人型ガラクトシアリドーシスの臨床経過

  坊亮輔, 粟野宏之, 永井正志, 冨岡和美, 田中司, 西山将広, 永瀬裕朗, 成田綾, 飯島一誠

  日本先天代謝異常学会, Sep. 2018, 日本先天代謝異常学会雑誌, 34, 201 - 201, Japanese


• 神戸大学における小児科と麻酔科の連携による脊髄性筋萎縮症のヌシネルセン治療

  永井 正志, 粟野 宏之, 松本 真明, 坊 亮輔, 冨岡 和美, 田中 司, 西山 将広, 前山 花織, 永瀬 裕朗, 小幡 典彦, 溝渕 知司, 西尾 久英, 飯島 一誠

  (一社)日本小児神経学会, May 2018, 脳と発達, 50(Suppl.) (Suppl.), S352 - S352, Japanese


• カーボカウントが1型糖尿病の血糖管理に有用であった7歳男児例

  松本真明, 粟野宏之, 坊亮輔, 冨岡和美, 前山花織, 西山将広, 永瀬裕朗, 飯島一誠

  01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 809, Japanese


• 先天性甲状腺機能低下症(CH)のフォロー中に偽性副甲状腺機能低下症と診断された1例

  坊亮輔, 粟野宏之, 松本真明, 永井正志, 冨岡和美, 田中司, 西山将広, 前山花織, 永瀬裕朗, 飯島一誠

  01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 816, Japanese


• 不明熱の精査中にRadiologically Isolated Syndromeが疑われた1例

  元生和宏, 冨岡和美, 松本真明, 永井正志, 坊亮輔, 前山花織, 田中司, 西山将広, 粟野宏之, 永瀬裕朗, 飯島一誠

  01 Apr. 2018, 日本小児科学会雑誌, 122(4) (4), 820, Japanese


• 2歳時に早期診断が出来た脊髄性筋萎縮症3a型の女児例

  永井正志, 粟野宏之, 松本真明, 坊亮輔, 冨岡和美, 田中司, 西山将広, 前山花織, 永瀬裕朗, 西尾久英, 飯島一誠

  01 Feb. 2018, 日本小児科学会雑誌, 122(2) (2), 460, Japanese


• 乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討

  前山花織, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, 高田哲, 松本真明, 永井正志, 坊亮輔, 冨岡和美, 西山将広, 粟野宏之, 永瀬裕朗, 飯島一誠, 西村範行

  2018, 日本小児科学会雑誌, 122(4) (4)


• 偶発的に発見された成長ホルモン産生下垂体腺腫の11歳男児例

  永井正志, 粟野宏之, 松本真明, 坊亮輔, 石田悠介, 冨岡和美, 田中司, 村尾真理子, 西山将広, 谷口理章, 飯島一誠

  2018, 日本小児内分泌学会学術集会プログラム・抄録集, 52nd


• 発作性運動誘発性ジスキネジアを呈した偽性副甲状腺機能低下症の一例

  坊亮輔, 粟野宏之, 西山将広, 永井正志, 冨岡和美, 田中司, 永瀬裕朗, 飯島一誠

  2018, 日本小児内分泌学会学術集会プログラム・抄録集, 52nd, 228, Japanese


• カルニチンのみで良好な経過をたどる慢性進行型メチルマロン酸血症同胞例

  坊亮輔, 粟野宏之, 永井正志, 松本真明, 富岡和美, 前山花織, 田中司, 西山将広, 永瀬裕朗, 飯島一誠

  12 Sep. 2017, 日本先天代謝異常学会雑誌, 33, 202, Japanese


• ビタミンB12反応性メチルマロン酸血症の1例

  永井正志, 粟野宏之, 松本真明, 坊亮輔, 冨岡和美, 前山花織, 西山将広, 西山敦史, 永瀬裕朗, 長谷川有紀, 飯島一誠

  01 May 2017, 日本小児科学会雑誌, 121(5) (5), 908‐909, Japanese


• 超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討

  松本真明, 粟野宏之, 永井正志, 坊亮輔, 冨岡和美, 前山花織, 西山将広, 永瀬裕朗, 森岡一朗, 飯島一誠

  01 Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 374, Japanese


• 近位筋優位の筋力低下から筋疾患が疑われたシャルコー・マリー・トゥース病2型

  永井正志, 粟野宏之, 松本真明, 坊亮輔, 冨岡和美, 前山花織, 西山将広, 港敏則, 永瀬裕朗, 飯島一誠

  01 Feb. 2017, 日本小児科学会雑誌, 121(2) (2), 380, Japanese


• CGMが診断・治療に有用であったダンピング症候群の乳児例

  松本真明, 粟野宏之, 福岡秀規, 永井正志, 坊亮輔, 冨岡和美, 前山花織, 田中司, 西山将広, 永瀬裕明, 飯島一誠

  2017, 日本内分泌学会雑誌, 93(2) (2)


• 新生児期に高TSH血症を示した偽性副甲状腺機能低下症の乳児期BMI

  坊亮輔, 粟野宏之, 永井正志, 松本真明, 富岡和美, 前山花織, 田中司, 西山将大, 永瀬裕朗, 飯島一誠

  2017, 日本小児内分泌学会学術集会プログラム・抄録集, 51st, 207, Japanese


• 幼児期からの糖・脂質代謝の経過をフォローしえたPTRF遺伝子変異による全身性脂肪萎縮症の一例

  松本真明, 粟野宏之, 廣田勇士, 永井正志, 坊亮輔, 冨岡和美, 前山花織, 西山将広, 李知子, 永瀬裕明, 八木麻理子, 竹島泰弘, 小川渉, 飯島一誠

  2017, 糖尿病(Web), 60(Suppl) (Suppl), S.379(J‐STAGE), Japanese


• ビタミンB12反応性を認めた軽症メチルマロニルCoAムターゼ欠損症の一例

  永井正志, 粟野宏之, 松本真明, 坊亮輔, 冨岡和美, 西山将広, 西山敦史, 永瀬裕朗, 長谷川有紀, 飯島一誠

  30 Sep. 2016, 日本先天代謝異常学会雑誌, 32, 191, Japanese


• グルタル酸血症１型

  BOU RYOUSUKE

  2016, 小児内科 増刊号, 48, 118 - 123, Japanese

  Introduction scientific journal

• CGMが診断・治療に有用であったダンピング症候群の乳児例

  松本 真明, Hiroyuki Awano, Fukuoka Hidenori, Fujita Kaori, Nagase Hiroaki, Nishiyama Masahiro, Iijima Kazumoto

  第27回臨床内分泌代謝Update, Nov. 2017, Japanese, 日本内分泌学会, 神戸, Domestic conference

  Poster presentation


• 症候性PKDを呈した偽性副甲状腺機能低下症の8歳女児例

  Hiroyuki Awano, Nishiyama Masahiro, 松本真明, Fujita Kaori, Nagase Hiroaki, Takada Satoshi, Iijima Kazumoto

  日本小児神経学会近畿地方会, Oct. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference

  Oral presentation


• カルニチンのみで良好な経過をたどる慢性進行型メチルマロン酸血症同胞例

  Hiroyuki Awano, 松本真明, Fujita Kaori, Nishiyama Masahiro, Nagase Hiroaki, Iijima Kazumoto

  第59回日本先天代謝異常学会, Oct. 2017, Japanese, 日本先天代謝異常学会, 埼玉, Domestic conference

  Poster presentation


• FreeStyle Libreの1型糖尿病患者での測定精度に関する検討

  松本 真明, 高橋 利和, Hiroyuki Awano, 中川 靖, Hirota Yushi, Ogawa Wataru, Iijima Kazumoto

  第17回日本先進糖尿病治療研究会, Oct. 2017, Japanese, 日本先進糖尿病治療研究会, 新潟, Domestic conference

  Oral presentation


• 不明熱の精査中にRadiologically Isolated Syndromeが疑われた1例

  元生和宏, 松本真明, Fujita Kaori, Nishiyama Masahiro, Hiroyuki Awano, Nagase Hiroaki, Iijima Kazumoto

  第272回日本小児科学会兵庫県地方会, Sep. 2017, Japanese, 日本小児科学会, 姫路, Domestic conference

  Oral presentation


• 新生児期に高TSH血症を示した偽性副甲状腺機能低下症の乳児期BMI

  Hiroyuki Awano, 松本真明, Nishiyama Masahiro, Fujita Kaori, Nagase Hiroaki, Iijima Kazumoto

  第51回日本小児内分泌学会, Sep. 2017, Japanese, 日本小児内分泌学会, 大阪, Domestic conference

  Poster presentation


• 内科・小児科の連携強化と 主食量の自己決定による サマーキャンプ中の血糖コントロールの改善

  松本 真明, Hiroyuki Awano, 竹内 健人, 山内 裕美子, 柏原 米男, Hirota Yushi, 石﨑 由美子, 宅見 徹, 高橋 利和, Ogawa Wataru, Iijima Kazumoto

  第23回日本小児・思春期糖尿病研究会年次学術集会, Jul. 2017, Japanese, 日本小児・思春期糖尿病研究会, 東京, Domestic conference

  Oral presentation


• 内科・小児科の連携強化と主食量の自己決定によるサマーキャンプ中の血糖コントロールの改善

  松本真明, Hiroyuki Awano, 竹内健人, 山内裕美子, 柏原米男, Hirota Yushi, 石﨑 由美子, 宅見徹, 高橋利和, Ogawa Wataru, Iijima Kazumoto

  第23回日本小児・思春期糖尿病研究会, Jul. 2017, Japanese, 日本小児・思春期糖尿病研究会, 東京, Domestic conference

  Poster presentation


• 乳幼児期における発達障害児の感覚特性についての検討～自閉症および知的障害特性との関連～

  Fujita Kaori, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, Takada Satoshi, Nishiyama Masahiro, Hiroyuki Awano, Nagase Hiroaki, Iijima Kazumoto, Nishimura Noriyuki

  第59回日本小児神経学会学術集会, Jun. 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference

  Oral presentation


• 幼児期からの糖・脂質代謝の経過をフォローしえたPTRF遺伝子変異による全身性脂肪萎縮症の一例（ポスター発表）

  松本真明, Hiroyuki Awano, Hirota Yushi, Fujita Kaori, Nishiyama Masahiro, 李 知子, Nagase Hiroaki, 八木麻理子, 竹島 泰弘, Ogawa Wataru, Iijima Kazumoto

  第60回日本糖尿病学会年次学術集会, May 2017, Japanese, 日本糖尿病学会, 名古屋, Domestic conference

  Poster presentation


• 幼児期からの糖・脂質代謝の経過をフォローしえたPTRF 遺伝子変異による全身性脂肪萎縮症の一例

  松本 真明, Hiroyuki Awano, Hirota Yushi, Fujita Kaori, Nishiyama Masahiro, 李 知子, Nagase Hiroaki, 八木 麻理子, 竹島 泰弘, Ogawa Wataru, Iijima Kazumoto

  第60回日本糖尿病学会年次学術集会, May 2017, Japanese, 日本糖尿病学会, 名古屋, Domestic conference

  Oral presentation


• 不明熱を契機にRadiologically Isolated Syndromeを呈した1例

  Nishiyama Masahiro, 松本真明, Fujita Kaori, Hiroyuki Awano, Nagase Hiroaki, Takada Satoshi, Iijima Kazumoto

  第61回 日本小児神経学会近畿地方会, May 2017, Japanese, 日本小児神経学会, 大阪, Domestic conference

  Oral presentation


• 乳幼児感覚プロファイルを用いた発達障害児の感覚特性に関する検討

  Fujita Kaori, 高木康子, 吉岡三惠子, 加藤威, 溝渕雅巳, 北山真次, Takada Satoshi, 松本真明, Nishiyama Masahiro, Hiroyuki Awano, Nagase Hiroaki, Iijima Kazumoto, Nishimura Noriyuki

  270回 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 尼崎, Domestic conference

  Oral presentation


• 超低出生体重児のSGA性低身長症に対する成長ホルモン治療の検討

  松本真明, Hiroyuki Awano, Fujita Kaori, Nishiyama Masahiro, Nagase Hiroaki, Morioka Ichiro, Iijima Kazumoto

  第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference

  Poster presentation


• 先天性甲状腺機能低下症（CH）のフォロー中に偽性副甲状腺機能低下症と診断された1例

  Hiroyuki Awano, 松本真明, Nishiyama Masahiro, Fujita Kaori, Nagase Hiroaki, Iijima Kazumoto

  日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 神戸, Domestic conference

  Oral presentation


• 近位筋優位の筋力低下から筋疾患が疑われたシャルコー・マリー・トゥース病2型

  Hiroyuki Awano, 松本真明, Fujita Kaori, Nishiyama Masahiro, 港敏朗, Nagase Hiroaki, Iijima Kazumoto

  第120回 日本小児科学会学術集会, May 2017, Japanese, 日本小児科学会, 東京, Domestic conference

  Poster presentation


• カーボカウントが1型糖尿病の血糖管理に有用であった7歳男児例

  松本 真明, Hiroyuki Awano, Fujita Kaori, Nishiyama Masahiro, Nagase Hiroaki, Iijima Kazumoto

  270回 日本小児科学会兵庫県地方会, May 2017, Japanese, 日本小児科学会, 尼崎, Domestic conference

  Oral presentation

• ジストロフィンDp71欠失がミトコンドリア機能に与える病態の解明

  坊 亮輔

  日本学術振興会, 科学研究費助成事業, 若手研究, 神戸大学, 01 Apr. 2023 - 31 Mar. 2026

  Duchenne型筋ジストロフィー(DMD)はDMD遺伝子異常により発症する進行性筋萎縮症である。DMDでは筋力低下以外にも全身臓器におよぶ多様な合併症を呈する。この多彩な臨床像の原因の一つとして、申請者らのグループはジストロフィンのアイソフォームの一つであるDp71に着目し、これまでにミトコンドリア機能の障害で確認される低身長がDp71欠損群で非欠失群に比較して高頻度に認められる点、Dp71がヒトのミトコンドリアに局在する点などを研究成果として報告してきた。これらの結果は、Dp71欠損がDMD患者のミトコンドリア機能を障害する可能性を示唆するものといえる。そのため、本研究では以下の3点を明らかにする。①Dp71欠損群でのミトコンドリア機能に関係する多種のバイオマーカーの変動を非欠損群と比較する、②患者由来の皮膚線維芽細胞、筋細胞を用いてDp71欠損の有無によるミトコンドリア機能の違いを比較する、③Dp71欠損群にみられるミトコンドリア機能を改善させる可能性のある薬剤を探索的に検討する。本研究の成果は、DMD患者の多彩な筋外合併症とミトコンドリア機能の間を繋ぐ病態生理の解明に寄与するとともに、未だ治療法の確立しないDMDの筋外合併症に対する新規薬剤ターゲットの可能性を明らかにすることとなる。


• Development of novel therapy due to correcting splicing error of patients with galactosialidosis

  Bo Ryosuke

  Japan Society for the Promotion of Science, Grants-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists, Kobe University, 01 Apr. 2019 - 31 Mar. 2022

  Galactosialiodosis is a rare lysosomal disease, caused by mutation in the CTSA gene. In Japanese cases, common variant, IVS7＋3A>G, has been identified, which was related to the milder phenotype. However, this mechanism of genotype and phenotype was not fully declared. At first, we analyzed the splicing pattern of this variant both in vivo and vitro. In previous report, this common variant produced exon 7 skipping and normal mRNA. However, our study revealed normal mRNA was not obtained in both. Furthermore, novel alternative splicing product including gt insertion was demonstrated. Skipping of exon 7 (92 bases) was assumed to cause nonsense medicated decay, but this product could be strongly related to the milder phenotype. We planed to clarify whether the specific antisense nucleotide can modify the splicing pattern of CTSA gene or not, but we can not obtain any sufficient effect However, this new splicing variant could be the novel target of therapy with galactosialidosis.