Severe Biotinidase Deficiency in a Newborn Due to a Novel Mutation: A Case Report

Hyperammonaemia is one of the common causes of early neonatal deterioration. Inborn errors of metabolism are frequent contributors to hyperammonaemia in newborns. Profound biotinidase deficiency is a rare cause that closely mimics inborn errors of metabolism. This report describes a rare case of profound biotinidase deficiency presenting as deterioration in the early neonatal period, characterised by hyperammonaemia, acidosis, hypoglycaemia, and ketosis. A three-day-old male patient presented with poor feeding and vomiting for six hours, along with respiratory difficulty for the same duration. The baby was hypotonic, exhibiting weak plantar and palmar grasp reflexes, poor sucking reflex, and reduced Moro reflex. The differential diagnoses considered included early onset sepsis and inborn errors of metabolism; however, the sepsis screen was negative. Blood investigations revealed severe metabolic acidosis, hyperammonaemia, hypoglycaemia, and ketonuria. Acyl carnitine levels (C5-OH) were above normal, and serum biotinidase levels were very low. This patient was diagnosed with severe biotinidase deficiency, and genetic analysis revealed a rare homozygous nonsense mutation in the Biotinidase (BTD) gene. This mutation led to a profound deficiency of the biotinidase enzyme, resulting in early neurological complaints. After the initial stabilisation of the baby, he was started on biotin supplementation and was placed under regular follow-up. Profound biotinidase deficiency should be considered as one of the causes of early neonatal deterioration. The management of profound deficiencies involves treating the acute presentation while correcting acid-base imbalances, hypoglycaemia, and related issues. The mainstay of long-term treatment is lifelong biotin supplementation.