Biotin‐responsive multiple carboxylase deficiency in an 8‐year‐old boy with normal serum biotinidase and fibroblast holocarboxylase‐synthetase activities

Abstract

An 8-year-old boy with late onset multiple carboxylase deficiency is described. Biotinidase deficiency and holocarboxylase-synthetase deficiency have been excluded. A very slow biochemical response to biotin was found. The decrease in urinary organic acid excretion followed first-order kinetics with a half-life of about 50 days. The initially low carboxylase activities in thrombocytes were increased but not normalized after 3 months of treatment.

Diagnosis and molecular analysis of an atypical case of holocarboxylase synthetase deficiency

“…In the present study, we identi®ed a mutation in the HCS gene of a patient who was originally reported as having late-onset MCD with normal serum biotinidase and ®broblast HCS activities [6]. The onset of symptoms in this patient occurred when he was 8 years old; the oldest reported onset of HCS de®ciency.…”

“…A patient who developed his ®rst episode of metabolic acidosis at 8 years and had the characteristic organic aciduria of MCD has been reported previously [6]. His clinical symptoms and organic aciduria were responsive to biotin therapy, although the decrease in his urinary 3-hydroxyisovalerate concentration was exceptionally slow.…”

“…The clinical ®ndings of a Swedish patient with HCS de®ciency have been previously described in detail [6]. In brief, at the age of 8 years, he was hospitalized due to an episode of reduced consciousness and confusion.…”

Mutations in the holocarboxylase synthetase geneHLCS

“…The amelioration of her biochemical and clinical abnormalities after biotin treatment started was relatively slow among patients with HLCS [Holme et al, 1988]. This mutation resulted in abnormal splicing with a decreased level of normal mRNA .…”

“…As previously noted, some patients homozygous for this mutation may be asymptomatic. In spite of a rather mild phenotype associated with IVS1015G4A among HLCS-deficient patients at the onset, the clinical responses to biotin treatment are slow and partial in some cases [Holme et al, 1988;Santer et al, 2003]. …”