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

• Published in: Journal of human genetics 2017-09, Vol.62 (9), p.809-814
• Main Authors: Bo, Ryosuke, Yamada, Kenji, Kobayashi, Hironori, Jamiyan, Purevsuren, Hasegawa, Yuki, Taketani, Takeshi, Fukuda, Seiji, Hata, Ikue, Niida, Yo, Shigematsu, Yosuke, Iijima, Kazumoto, Yamaguchi, Seiji
• Format: Article
• Language: English
• Subjects: 3-Hydroxyacyl-CoA dehydrogenase; Adolescent; Asian Continental Ancestry Group - genetics; Cardiomyopathies - diagnosis; Cardiomyopathies - genetics; Child; Child, Preschool; Clinical aspects; Enzyme Activation; European Continental Ancestry Group - genetics; Family; Fatty liver; Female; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Genotype; Humans; Hypocalcemia; Hypoparathyroidism; Infant; Infant, Newborn; Lipid Metabolism, Inborn Errors - diagnosis; Lipid Metabolism, Inborn Errors - genetics; Male; Metabolic disorders; Mitochondria; Mitochondrial Myopathies - diagnosis; Mitochondrial Myopathies - genetics; Mitochondrial Trifunctional Protein - deficiency; Mitochondrial Trifunctional Protein - genetics; Mitochondrial Trifunctional Protein, alpha Subunit - genetics; Mitochondrial Trifunctional Protein, alpha Subunit - metabolism; Mitochondrial Trifunctional Protein, beta Subunit - genetics; Mitochondrial Trifunctional Protein, beta Subunit - metabolism; Mutation; Neonates; Nervous System Diseases - diagnosis; Nervous System Diseases - genetics; Oxidation; Patients; Peripheral neuropathy; Pregnancy; Protein deficiency; Rhabdomyolysis - diagnosis; Rhabdomyolysis - genetics; White people
• ISSN: 1434-5161; 1435-232X
• DOI: 10.1038/jhg.2017.52

Mitochondrial trifunctional protein (TFP) deficiency is an inherited metabolic disorder of mitochondrial fatty-acid oxidation. Isolated long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency is often reported in Caucasian countries due to a common mutation. However, the molecular and clinical basis of complete TFP deficiency has not been extensively reported. In this study, 14 Japanese cases (13 families) with complete TFP deficiency, including 9 previously reported cases, were analyzed to clarify the clinical and molecular characteristics of TFP deficiency. The clinical types of the 14 patients were as follows: 12 cases of neonatal (n=7) or myopathic (n=5) types and 2 cases of intermediate type. Peripheral neuropathy was found in four cases and hypocalcemia due to hypoparathyroidism, which is rarely reported in Caucasian patients, had developed in four cases. Maternal hemolysis, elevated liver enzymes and low platelet count syndrome and acute fatty liver of pregnancy were noted in two and one mothers, respectively. Fourteen mutations were identified in 26 alleles in Japanese patients, including two novel mutations (HADHA: c.361C>T, and HADHA-HADHB: g.26233880_ 26248855del), although no common mutations were found. This study suggests that the molecular and clinical aspects of Japanese patients with TFP deficiencies differ from those of Caucasian patients.