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.