Holocarboxylase synthetase deficiency: report of one case.
Holocarboxylase synthetase (HCS) is an enzyme that catalyzes biotin incorporation into carboxylases, and its deficiency causes biotin-responsive multiple carboxylase deficiency. We report a patient who had his first episode at 32 months of age. The main clinical findings were a characteristic rash, projectile vomiting, progressive consciousness loss, organophosphate order, and hypotension. Laboratory examinations showed metabolic acidosis with ketolactic acidosis, hyperammonemia, and urine organic acid profile suggestive of a biotin utilization abnormality consistent with multiple carboxylase deficiency. Nucleotide sequence analysis of the biotinidase gene of the patient revealed negative finding, however, analysis of HCS gene found a homozygous 1809C->T (R508W) mutation. R508W is a rare mutation in Taiwanese HCS deficiency patients, which is associated with the late-onset phenotype. The patient responded dramatically to biotin, and has remained normal growth and development during more than three years of follow-up. Therefore, a high index of suspicion for timely diagnosis and treatment could prevent severe complications.
Chou
I-Ching
IC
Department of Pediatrics, China Medical University Hospital, Taichung.
Wang
Chung-Shing
CS
Lin
Wei-Der
WD
Lin
Hsin-Chen
HC
Tsai
Chang-Hai
CH
Wang
Tso-Ren
TR
Tsai
Fuu-Jen
FJ
D001710:Biotin / Q000627:therapeutic use; D019731:Carbon-Nitrogen Ligases / Q000235:genetics*; D002675:Child, Preschool; D028922:Holocarboxylase Synthetase Deficiency / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation
D001710:Biotin; D019731:Carbon-Nitrogen Ligases; C023312:holocarboxylase synthetases