In
multiple carboxylase deficiency (MCD), the
biotin-dependent carboxylases have decreased activity due to either
biotinidase deficiency or holocarboxylase
synthetase (HS) deficiency. We report the case of two siblings from Ghana, the first of which presented shortly after birth with profound
lactic acidosis and a urine organic
acid profile consistent with MCD. In the first sibling, treatment with pulverized
biotin tablets (20 mg) was begun immediately, but the patient died
at 10 days of age from
cardiac arrest secondary to refractory
metabolic acidosis. Autopsy revealed a
biotin bezoar. Sequencing of HCLS showed homozygosity for a novel missense variant (p.G241W). The second sibling had a similar presentation at birth: severe
metabolic acidosis and respiratory distress. A urine organic
acid profile was consistent with HS deficiency; he was treated with
biotin powder (20 mg), and after 24 h, the
lactate decreased significantly; by day 5 of life, the patient was tolerating 40 mg of
biotin, feeding by mouth and off all other medications and support. This is the first report of the p.G241W mutation. To our knowledge, this is also the first mutation described in West African patients with HS deficiency and the cases demonstrate that it is
biotin responsive. Additionally, our experience suggests that the powdered form of
biotin supplementation may be more digestible than
tablets for the treatment of severe neonatal HS deficiency.