Deficiency of holocarboxylase synthetase presents in more than 50% of cases in the
neonatal period with tachypnea or Kussmaul breathing, hypotonia, and
seizures. Severe metabolic acidosis with ketosis and hyperammonemia.
Untreated patients and those with less severe defects present with mental
retardation, hair loss, and skin lesions (erythematous rash often with
superinfection with Candida). Deficiency of biotinidase presents later in infancy or childhood. Lethargy,
hypotonia, seizures, ataxia; respiratory problems (apnea/hyperventilation,
frequent stridor). Skin manifestations such as periorificial eczematoid
dermatitis and alopecia are less common. Intermittent organic aciduria.
Immune deficiency leads to recurrent infections. If untreated, psychomotor
delay and permanent neurologic deficit (hearing loss, optic atrophy).
Treatment: In both conditions there is a dramatic response to biotin, with resolution
of clinical and biochemical abnormalities but not fixed neurologic sequelae.
The dose of biotin varies from 2.5 to 5 mg/week (partial deficiency in
biotinidase) to 2.5 to 10 mg/day (profound deficiency in biotinidase) or
even more; 10 to 20 mg/day in case of holocarboxylase deficiency.