Ten patients with biotin-responsive basal ganglia disease are reported from the King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia, and Brown University School of Medicine, Hasbro Children’s and Rhode Island Hospitals, Providence, RI. All were of Middle Eastern, mainly Saudi ethnic origin, all were children of consanguinous marriages, and all had a history of siblings with a similar disease that was undiagnosed and resulted in death in 17 children. Patients diagnosed and treated were followed for 3 to 10 years. Symptoms of an acute or subacute encephalopathy, presenting between ages 1 and 14 years, usually pre-school, included a prodrome of confusion and lethargy followed by coma and vomiting, and progressing to dysarthria and dysphagia/drooling (8 patients), seizures (5), facial or gaze paralysis (4), dystonia and rigidity (10), opisthotonus (3), and quadriparesis (6). Following treatment with biotin, 5-10 mg/kg/day, symptoms resolved without neurologic sequelae. They returned when biotin was discontinued, sometimes resulting in residual paraparesis, dystonia, or mild mental retardation, despite reintroduction of biotin. The presumed defect in biotin metabolism or transporter mechanism was undetermined since enzyme assays for biotinidase and carboxylase, in addition to other biochemical, toxicological, and viral studies, were normal. Brain MRI always showed bilateral central necrosis of the head of the caudate nucleus and complete or partial involvement of the putamen, and lesions were unchanged after prolonged biotin therapy. 
COMMENT. A diagnosis of biotin-responsive basal ganglia syndrome should be considered in children born to consanguinous parents, and presenting as an acute or subacute encephalopathy, with confusion, vomiting and seizures, followed by symptoms of brainstem and extrapyramidal involvement, and accompanied by caudate and putamen necrosis on MRI. The first patient with this syndrome, diagnosed by Dr Edward Rabe, now of Maine, USA, had failed to respond to trials of acyclovir, thiamine, carnitine, phenobarbital and diazepam, but showed immediate improvement when biotin was introduced in megadoses, 10-40 x greater than those required in biotin deficiency states. Characteristic signs of the infantile type of biotin encephalopathy, including skin rash, alopecia, ketoacidosis, and organic acidemia, were absent, and presumably, the smaller biotin doses (5-10 mg daily) employed in cases of biotin deficiency were found ineffective. A defect in biotin transport across the blood-brain barrier was postulated, since assays of biotinidase and carboxylase were normal. See Progress in Pediatric Neurology I, II, & III, (PNB Publishers) for reports of neonatal and infantile biotin encephalopathy. This apparent nonspecific effect of biotin in cases of idiopathic familial progressive encephalopathy might prompt trials of megadose biotin in children with chronic refractory encephalopathies.