We present a new case of holocarboxylase
synthetase (HCS) deficiency, a rare autosomal recessive metabolic disorder, causing the "early-onset" form of
multiple carboxylase deficiency. The patient was born at term of healthy consanguineous parents after an uncomplicated pregnancy. On the 2nd day of life she refused oral feeding, became tachydyspnoeic and showed excessive
weight loss. Laboratory studies showed
metabolic acidosis, marked lactic acidaemia, hyperammonaemia and increased urinary excretion of
3-hydroxyisovaleric acid,
3-methylcrotonylglycine, 3-hydroxpropionic
acid and
methylcitric acid.
Peritoneal dialysis combined with oral supplementation of
biotin (10 mg/day) started on the 3rd day of life resulted in rapid clinical recovery and normalisation of biochemical parameters. HCS deficiency was established in lymphocytes and skin fibroblasts. The activities of all
biotin-dependent carboxylases were severely decreased in fibroblasts grown in medium with moderate
biotin concentration (10(-8) mol/l) but normal in a high
biotin medium (10(-5) mol/l). Mitochondrial carboxylase activities in lymphocytes were 23%-29% of mean normal during
therapy with 20 mg of
biotin/day, with the higher dose of 40 mg/day they were within (3-methylcrotoryl-
CoA carboxylase, pyruvate carboxylase) or slightly below (
propionyl-CoA carboxylase) the normal range. At the age of 3 years the patient's physical and psychomotor development are normal. Early
biotin supplementation should be considered in newborns with
lactic acidosis and organoaciduria until a final diagnosis has been established. Furthermore, the required individual dose of
biotin has to be carefully evaluated biochemically for the individual patient.