A case of biotin responsive infantile encephalopathy is reported from the Department of Pediatrics and Child Neuropsychiatry, University of Verona, Italy; and Hopital des Enfants Malades, Paris, France. At one month of age the infant developed dermatitis of the ears. At two months she began to have tonic clonic seizures occurring several times a day and refractory to treatment with carbamazepine, phenobarbital, phenytoin, clonazepam, nitrazepam, ACTH, and hydrocortisone. Seizure frequency increased up to ten per day. At three months, she became hypotonic and a CT scan showed enlargement of cortical sulci and lateral ventricles. At four months she was very lethargic and floppy, reflexes were hyperactive, and plantar responses were extensor. Her behavior was autistic-like and her scalp hair was sparse. The urine examination showed an increased excretion of 2-ketoglutaric acid and 3-hydroxy-isovaleric acid. Serum biotinidase activity was 0.15 nmol min−1 ml−1 (normal range 5.2). Father’s biotinidase activity was 0.31 (8% of normal) and the mother’s 0.42 (10% of normal). An electroencephalogram showed frequent independent spikes of variable amplitude prominent in the left posterior temporal region and numerous EEG seizures. Within 36 hours of starting biotin therapy 5 mg BD there was dramatic clinical improvement; the infant became responsive to surrounding stimuli, seizures were controlled and antiepileptic treatment was reduced to only phenobarbital 15 mg BD. After ten days of treatment the urinary examination was normal and the EEG showed a well organized background activity and no paroxysmal abnormalities. At two years four months the neurological exam was normal, the CT scan and EEG normal, and the dose of biotin was at 7.5 mg a day. The authors suggest a therapeutic trial of biotin in all drug resistant infantile seizures. 
COMMENT. Two forms of biotin responsive encephalopathy are reported. 1) neonatal holocarboxalase synthetase deficiency (HCSD) and 2) late onset infantile or juvenile biotinidase deficiency (BD). HCSD patients have vomiting, lethargy, and hypotonia associated with metabolic ketoacidosis, hyperammonemia, and organic acidemia. BD infants present with seizures, ataxia, skin rash and alopecia. Seizures are reported in two of five HCSD cases and in 15 of 28 BD cases. The authors stress that the epileptic symptomatology may be the first clinical feature in BD cases. Myoclonias, auditory myoclonus, and repetitive startles documented in the present case were thought to be nonepileptic in nature.