title: Biotin-responsive basal ganglia disease revisited: clinical, radiologic, and genetic findings.
abstract: OBJECTIVE
  To investigate the clinical, genetic, and neuroradiologic data of biotin-responsive basal ganglia disease (BBGD) and clarify the disease spectrum.
  
  
  METHODS
  We first investigated all patients attending our Division of Pediatric Neurology with a genetically proven diagnosis of BBGD between 2009 and 2011. All patients underwent a detailed medical history and clinical examination, extensive laboratory investigations including genetic tests, and brain MRI. Finally, we conducted a systematic review of the literature.
  
  
  RESULTS
  We enrolled 10 patients meeting the diagnostic criteria for BBGD, and analyzed the data on 14 patients from 4 previous reports. The BBGD occurred predominantly in preschool/school-aged patients in the Saudi population, but it was also observed in other ethnic groups. The typical clinical picture consisted of recurrent subacute encephalopathy leading to coma, seizures, and extrapyramidal manifestations. The brain MRI typically showed symmetric and bilateral lesions in the caudate nucleus and putamen, infra- and supratentorial brain cortex, and in the brainstem. Vasogenic edema characterized the acute crises as demonstrated by diffusion-weighted imaging/apparent diffusion coefficient MRI. Atrophy and gliosis in the affected regions were observed in patients with chronic disease. Early treatment with a combination of biotin and thiamine resulted in clinical and neuroradiologic improvement. Death and neurologic sequelae including dystonia, mental retardation, and epilepsy were observed in those who were not treated or were treated late.
  
  
  CONCLUSIONS
  BBGD is an underdiagnosed pan-ethnic treatable condition. Clinicians caring for patients with unexplained encephalopathy and neuroimaging showing vasogenic edema in the bilateral putamen and caudate nuclei, infra- and supratentorial cortex, and brainstem should consider this disorder early in the hospital course because a therapeutic trial with biotin and thiamine can be lifesaving.
authors.affiliation: Division of Pediatric Neurology, Department of Pediatrics, Riyadh Military Hospital, Kingdom of Saudi Arabia.
authors.forename: Brahim
authors.initials: B
authors.lastname: Tabarki
authors.forename: Shatha
authors.initials: S
authors.lastname: Al-Shafi
authors.forename: Saad
authors.initials: S
authors.lastname: Al-Shahwan
authors.forename: Zeeshan
authors.initials: Z
authors.lastname: Azmat
authors.forename: Amel
authors.initials: A
authors.lastname: Al-Hashem
authors.forename: Nawal
authors.initials: N
authors.lastname: Al-Adwani
authors.forename: Nabil
authors.initials: N
authors.lastname: Biary
authors.forename: Mohamed
authors.initials: M
authors.lastname: Al-Zawahmah
authors.forename: Sonia
authors.initials: S
authors.lastname: Khan
authors.forename: Giulio
authors.initials: G
authors.lastname: Zuccoli
mesh_terms: D001284:Atrophy; D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D038524:Diffusion Magnetic Resonance Imaging; D005260:Female; D005911:Gliosis / Q000473:pathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D011859:Radiography; D012189:Retrospective Studies; D012640:Seizures / Q000209:etiology; D013831:Thiamine / Q000627:therapeutic use; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human; D014815:Vitamins; D013831:Thiamine