Clinical, biochemical and genetic features of 13 children with maple syrup urine disease

Abstract

Objective To explore the clinical, treatment, and genetic findings of maple syrup urine disease (MSUD). Methods Six boys and 7 girls out of 13 patients from unrelated Chinese families were enrolled.MSUD was detected in one patient by newborn screening.Twelve patients had the onset from the age of 2 days to 1 year and 6 months.They presented vomiting, feeding difficulties, lethargy, coma and psychomotor retardation.Blood amino acids were analyzed, and gene analysis was performed. Results The patients were hospitalized, age ranging from 16 days to 1 year and 8 months.Among them, 11 cases were of classical type and had very early onset.Only 1 patient with interme-diate type had relatively late onset.The girl detected by newborn screening was treated at the age of 9 days.She was healthy now with unknown MSUD type.Eleven classical MSUD children were diagnosed because of significantly elevated blood branched chain aminoacids (leucine, isoleucine, valine and alloisoleucine). Fourteen mutations were found from 10 patients who accepted gene analysis, including 7 mutations in BCKDHA gene (c.178G>T, c. 491T>C, c. 659C>T, c. 740A>G, c. 1214_1219dupCCAACC, c.1234G>A and IVS6+ 1delG0), 5 mutations in BCKDHB gene (c.482T>G, c. 508C>T, c. 767A>G, c. 768C>G and IVS4, -2A>C), 2 mutations in DBT gene (c.1A>G and c. 1150A>G). Two patients had normal development.One patient died from respiratory failure at the age of 4 years and 6 months. Conclusions MSUD is a rare life-threatening disorder which leads to metabolic crisis and brain damage with high mortality.Neonatal screening, early diagnosis and dietary treatment are crucial to improve the outcome. Key words: Maple syrup urine disease; Branched chain amino acid; BCKDHA gene; BCKDHB gene; DBT gene