Family Case of Biotin-Thiamine-Responsive Basal Ganglia Disease

Background: Thiamine-biotin-dependent disease of the basal ganglia is a rare neurodegenerative hereditary disease caused by mutations in the SLC19A3 gene. Most cases are described among people from Saudi Arabia.

Case studies: A young pregnant woman at 12 weeks gestation presented with aggravated anamnesis. Her first child died at the age of 1.5 years after suffering a severe metabolic crisis at 9 months. The parents are second-cousin siblings belonging to the Turkic ethnic group. High-throughput sequencing of the proband revealed a pathogenic homozygous variant c.223GA, p.D75N in the SLC19A3 gene and two compound-heterozygous variants c.1208CT, p.A403V and c.529GA, p.V177M in the PAH gene. Prenatal analysis of the foetus revealed the presence of the same biallelic variants in the SLC19A3 and PAH genes. The boy was born at term and received thiamine (100 mg/kg/day) from birth and biotin after 4 months (10 mg/day). Four years later, the woman gave birth to another boy, this time without a prenatal diagnosis and the child was immediately given thiamine (100 mg/kg/day). Further DNA diagnostics revealed a family homozygous variant in the SLC19A3 gene and a heterozygous c.1208CT variant in the PAH gene in the third child. Currently, both children continue to receive daily thiamine (100 mg/kg/day) and biotin (10 mg/day) and have developed accordingly. Brain MRIs have revealed no pathology. Interestingly, the blood phenylalanine level in the older child was within the reference values according to neonatal screening and remains within the normal range (0−120 µmol/l) against the background of a normal diet. In cases of a family history, thiamine-biotin-dependent basal ganglia disease should be considered despite its rare occurrence. The earliest possible introduction of thiamine and biotin with good compliance increases the chances of preventing the development of neurodegenerative processes.