J Ye1, T Wang, L S Han, W J Qiu, H W Zhang, Y F Zhang, X L Gao, Y Wang, X F Gu. 1. Department of Pediatric Endocrinology and Genetic Metabolism, Xin Hua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, 1665 Kong Jiang Road, Shanghai, 200092, China.
Abstract
OBJECTIVE: To report the clinical course and explore the gene mutation spectrum of four Chinese children with biotinidase deficiency. METHODS: Four Chinese patients aged 4 months to 8 years were referred to this study. Tandem mass spectrometry, gas chromatography-mass spectrometry and the determination of biotinidase activities were performed for selective screening of biotinidase deficiency. Four patients with biotinidase deficiency were diagnosed, treated with biotin and followed. RESULTS: (1) Four patients with biotinidase deficiency were diagnosed by characteristic metabolites, such as elevated blood levels of 3-hydroxyisovalerylcarnitine (6.22 +/- 3.1 mumol/L), elevated 3-methylcrontonylglycine, methylcitrate and 3-hydroxypropionate in urine and very low biotinidase activities. (2) These patients have been treated with biotin for 1-8 years; two of them still have mental retardation, and two have irreversible hearing or vision disability. (3) In the four patients, six different mutations in the biotinidase gene were identified: c.98G:del7ins3, c.1369G>A (p. V457M), c.1384delA, c.1493_1494insT, c.1284C>A (p.Y428X) and c.1157G>A (p.W386X). The latter four mutations are novel variations. Seven out of eight mutations are located on exon 4 of the biotinidase gene. CONCLUSIONS: Early recognition of biotinidase deficiency is crucial to avoid permanent damage. Determination of biotinidase activity should be included in neonatal screening in China. Exon 4 may be a hot-spot for biotinidase gene mutations in Chinese patients. Four novel gene variations may be disease-causing mutations and should be confirmed by expression studies.
OBJECTIVE: To report the clinical course and explore the gene mutation spectrum of four Chinese children with biotinidase deficiency. METHODS: Four Chinese patients aged 4 months to 8 years were referred to this study. Tandem mass spectrometry, gas chromatography-mass spectrometry and the determination of biotinidase activities were performed for selective screening of biotinidase deficiency. Four patients with biotinidase deficiency were diagnosed, treated with biotin and followed. RESULTS: (1) Four patients with biotinidase deficiency were diagnosed by characteristic metabolites, such as elevated blood levels of 3-hydroxyisovalerylcarnitine (6.22 +/- 3.1 mumol/L), elevated 3-methylcrontonylglycine, methylcitrate and 3-hydroxypropionate in urine and very low biotinidase activities. (2) These patients have been treated with biotin for 1-8 years; two of them still have mental retardation, and two have irreversible hearing or vision disability. (3) In the four patients, six different mutations in the biotinidase gene were identified: c.98G:del7ins3, c.1369G>A (p. V457M), c.1384delA, c.1493_1494insT, c.1284C>A (p.Y428X) and c.1157G>A (p.W386X). The latter four mutations are novel variations. Seven out of eight mutations are located on exon 4 of the biotinidase gene. CONCLUSIONS: Early recognition of biotinidase deficiency is crucial to avoid permanent damage. Determination of biotinidase activity should be included in neonatal screening in China. Exon 4 may be a hot-spot for biotinidase gene mutations in Chinese patients. Four novel gene variations may be disease-causing mutations and should be confirmed by expression studies.
Authors: A Morrone; S Malvagia; M A Donati; S Funghini; F Ciani; I Pela; A Boneh; H Peters; E Pasquini; E Zammarchi Journal: Am J Med Genet Date: 2002-07-22
Authors: A Yamaguchi; M Fukushi; O Arai; Y Mizushima; Y Sato; Y Shimizu; K Tomidokoro; N Takasugi Journal: Tohoku J Exp Med Date: 1987-08 Impact factor: 1.848
Authors: Division of Biochemistry and Metabolism, Medical Genetics Branch Chinese Medical Association; Division of Genetics and Metabolism, Child Diseases and Health Care Branch Chinese Association for Maternal and Child Health; Division of Genetics and Metabolism, Rare Diseases Committee of Beijing Medical Association Journal: Zhejiang Da Xue Xue Bao Yi Xue Ban Date: 2022-02-25
Authors: Taciane Borsatto; Fernanda Sperb-Ludwig; Samyra E Lima; Maria R S Carvalho; Pablo A S Fonseca; José S Camelo; Erlane M Ribeiro; Paula F V de Medeiros; Charles M Lourenço; Carolina F M de Souza; Raquel Boy; Têmis M Félix; Camila M Bittar; Louise L C Pinto; Eurico C Neto; Henk J Blom; Ida V D Schwartz Journal: PLoS One Date: 2017-05-12 Impact factor: 3.240