Biotin-thiamine-responsive basal ganglia disease

Ali Mir, Rami Alhazmi  and Raidah Albaradie.  Biotin-Thiamine-Responsive Basal Ganglia Disease—A Treatable Metabolic Disorder .  Pediatric Neurology.  In press.

This two-year-old girl presented with a nine day history of excessive sleepiness, inability to walk, ptosis, irritability, and tonic posturing of extremities. There was no history of fever or recent illness. Magnetic resonance imaging of the brain was performed, and she received intravenous immunoglobulin and pulse corticosteroids for presumed acute disseminated encephalomyelitis (ADEM). The lactate peak on magnetic resonance spectroscopy raised the suspicion of mitochondrial disease. Repeat imaging three weeks later showed improvement, and she returned to baseline. She presented two months later with similar symptoms following gastroenteritis and fever. She was again treated with pulse steroids for suspected recurrent ADEM, but biotin-thiamine-responsive basal ganglia disease (BTBGD) was also considered. Biotin and thiamine were given. Genetic testing detected a pathogenic homozygous c.1264A>G (p.Thr422Ala) variant in SLC19A3. At her 10-month follow-up visit, she was asymptomatic with a normal examination .

BTBGD is an underdiagnosed treatable metabolic disorder. It is an autosomal recessive disorder caused by a mutation in the SLC19A3 gene. It typically presents in children aged three to ten years and is usually preceded by febrile illness.  It is characterized by recurrent subacute encephalopathy, seizures, ataxia, dystonia, supranuclear facial palsy, and external ophthalmoplegia, and if left untreated, can lead to coma and even death.  The central necrosis of both heads of the caudate and complete or partial, involvement of the putamina are consistent radiographic findings during the initial acute encephalopathy and may persist. 

Early recognition is important to avoid delay and misdiagnosis, as the clinical picture could look like ADEM or mitochondrial disease. Prompt administration of biotin and thiamine early in the disease course results in partial or complete improvement.