Chapter title |
Japanese Male Siblings with 2-Methyl-3-Hydroxybutyryl-CoA Dehydrogenase Deficiency (HSD10 Disease) Without Neurological Regression
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Chapter number | 570 |
Book title |
JIMD Reports, Volume 32
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Published in |
JIMD Reports, June 2016
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DOI | 10.1007/8904_2016_570 |
Pubmed ID | |
Book ISBNs |
978-3-66-254384-9, 978-3-66-254385-6
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Authors |
Akagawa, Shohei, Fukao, Toshiyuki, Akagawa, Yuko, Sasai, Hideo, Kohdera, Urara, Kino, Minoru, Shigematsu, Yosuke, Aoyama, Yuka, Kaneko, Kazunari, Shohei Akagawa, Toshiyuki Fukao, Yuko Akagawa, Hideo Sasai, Urara Kohdera, Minoru Kino, Yosuke Shigematsu, Yuka Aoyama, Kazunari Kaneko |
Editors |
Eva Morava, Matthias Baumgartner, Marc Patterson, Shamima Rahman, Johannes Zschocke, Verena Peters |
Abstract |
2-Methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency (HSD10 disease) is a rare X-linked disorder caused by a mutation in the HSD17B10 gene. Fewer than 30 patients with this disorder have been reported worldwide. The classical infantile form of HSD10 disease is characterized by a progressive neurodegenerative course with retinopathy and cardiomyopathy, although HSD10 disease has broad clinical heterogeneity. However, several male patients have not shown neurological regression. Here, we describe two Japanese siblings with HSD10 disease without neurological regression. A 4-year-old boy presented with unconsciousness due to severe hypoglycemia. Laboratory testing on admission showed mild metabolic acidosis and mild hyperammonemia. Urinary organic acid analysis in the acute phase showed elevated excretion of 2-methyl-3-hydroxybutyric acid, tiglylglycine, and ketones. However, 2-methylacetoacetate was not elevated. HSD10 disease was suspected based on urinary organic acid data. The patient had a novel hemizygous c.470C>T (p.A157V) mutation in the HSD17B10 gene. His mother was a heterozygous carrier of this mutation. The patient's older brother also had the c.470C>T (p.A157V) mutation. Neurological development was normal at the time of evaluation. The pilot newborn screening results using tandem mass spectrometry of the proband were reevaluated retrospectively and showed a high C5:1 carnitine level of 0.070 nmol/mL (upper cutoff limit, 0.05 nmol/mL) and a normal C5-OH carnitine level of 0.290 nmol/mL (upper cutoff limit, 1.0 nmol/mL). His affected brother and another patient with the atypical form of HSD10 disease having p.A154T also showed elevated C5:1 but not C5-OH in serum acylcarnitine analysis. Thus, these data suggested that some patients with this disorder may be identified using newborn screening. |
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United States | 1 | 100% |
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Members of the public | 1 | 100% |
Mendeley readers
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Unknown | 10 | 100% |
Demographic breakdown
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Student > Ph. D. Student | 2 | 20% |
Unspecified | 1 | 10% |
Lecturer | 1 | 10% |
Student > Bachelor | 1 | 10% |
Student > Doctoral Student | 1 | 10% |
Other | 2 | 20% |
Unknown | 2 | 20% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 2 | 20% |
Unspecified | 1 | 10% |
Agricultural and Biological Sciences | 1 | 10% |
Biochemistry, Genetics and Molecular Biology | 1 | 10% |
Social Sciences | 1 | 10% |
Other | 1 | 10% |
Unknown | 3 | 30% |