Biotin responsive seizures and encephalopathy due to biotinidase deficiency.

Biotinidase deficiency is a disorder of multiple carboxylase deficiency with an autosomal recessive mode of inheritance and was first described by Wolf and colleagues in 1983 The reported incidence in various neonatal screening programs worldwide is 1:60,000 live births. Biotin, a vitamin B complex is necessary to activate the carboxylase enzymes system. The carboxylase enzymes are essential for the metabolism of amino acids, carbohydrate and fatty acids. Biotin is normally required in a very small quantity as most of it is re-cycled by biotinidase enzyme. Biotinidase deficiency results in the depletion of body biotin stores, thus leading to the failure of carboxylase enzymes causing severe metabolic consequences. Biotin deficiency is characterized by acute metabolic encephalopathy, neuro-developmental delay, anti-epileptic drug resistant seizure disorder, muscular hypotonia, alopecia and skin rash.

A boy aged three months presented with history of recurrent seizures since 35 days of age. He used to have five to six convulsive seizures a day, each lasting for five minutes. He was extremely lethargic and sleepy most of the time with poor cry, sucking, and motor activity. Three of his siblings had died with similar illness. Seizures were uncontrolled with phenobabitone and clonazepam. He was tried on pyridoxine without any effect. On examination, there were no dysmorphic features or neuro-cutaneous markers. The scalp hair was very thin and scanty and the eye brows and eye lashes were virtually absent. He also had nappy dermatitis. Neurological examination revealed a lethargic child with dull and expressionless face. There was no eye contact and he could not track the moving objects. There was generalized hypotonia with marked head lag. The neonatal reflexes were very sluggish. The deep tendon reflexes were exaggerated. Rest of the systemic examination was unremarkable. Investigations revealed mildly elevated ammonia 127 micromole/L (normal 16 – 60 micromole/L) and lactate 3.9 micromole/L (normal 0.5 – 2.0 micromole/L). Blood sugar, renal, hepatic and bone profile were normal and no keto-acidosis. EEG revealed burst suppression pattern and asynchrony, multi-focal spike discharges consisting with early infantile encephalopathy. Magnetic resonance imaging (MRI) of brain revealed diffuse white matter changes with marked cortical atrophy. Tandem mass spectrometry revealed high C5 hydroxycarnitine levels. The urine organic acid profile showed marked increase of 3-hydroxyisovarelate,