title: Biotin-responsive basal ganglia disease should be renamed biotin-thiamine-responsive basal ganglia disease: a retrospective review of the clinical, radiological and molecular findings of 18 new cases.
abstract: BACKGROUND
  Biotin-responsive basal ganglia disease (BBGD) is an autosomal recessive neurometabolic disorder. It is characterized by sub acute encephalopathy with confusion, seizure, dysarthria and dystonia following a history of febrile illness. If left untreated with biotin, the disease can progress to severe quadriparesis and even death.
  
  
  METHODS
  A retrospective chart review of 18 patients with BBGD from two tertiary institutions describing their clinical, magnetic resonance imaging and molecular findings was conducted.
  
  
  RESULTS
  Eighteen children from 13 families seen over a period of nine years (2003-2012) were included. (Age range: 14month to 23 years, M: F: 1:1). The clinical features included sub acute encephalopathy, ataxia (n= 18), seizures (n= 13) dystonia (n=12) ,dysarthria (n= 9), quadriparesis and hyperreflexia (n=9). Magnetic resonance imaging demonstrated abnormal signal intensity with swelling in the basal ganglia during acute crises (n= 13/13) and atrophy of the basal ganglia and necrosis during follow up (n= 13/13). One-third of the present patients showed the recurrence of acute crises while on biotin therapy alone, but after the addition of thiamine, crises did not recur. All of the patients have a homozygous missense mutation in exon 5 of the SLC19A3 gene. The frequency of acute crises, delay in diagnosis and initiation of treatment significantly influenced the outcome. On follow up, four patients died, two had spastic quadriplegia, six had normal outcome and the rest had speech and motor dysfunctions.
  
  
  CONCLUSIONS
  Clinicians should suspect BBGD in any child presenting with sub acute encephalopathy, abnormal movement and MRI findings as described above. Both biotin and thiamine are essential for disease management. Since biotin alone could not prevent the recurrence of crises in some patients, a more appropriate term to describe the disease would be biotin-thiamine-responsive basal ganglia disease (BTBGD).
authors.affiliation: Division of Genetics, Department of Pediatrics, King Abdulaziz Medical City, Riyadh, Saudi Arabia. dralfadhel@yahoo.com
authors.forename: Majid
authors.initials: M
authors.lastname: Alfadhel
authors.forename: Makki
authors.initials: M
authors.lastname: Almuntashri
authors.forename: Raafat H
authors.initials: RH
authors.lastname: Jadah
authors.forename: Fahad A
authors.initials: FA
authors.lastname: Bashiri
authors.forename: Muhammad Talal
authors.initials: MT
authors.lastname: Al Rifai
authors.forename: Hisham
authors.initials: H
authors.lastname: Al Shalaan
authors.forename: Mohammed
authors.initials: M
authors.lastname: Al Balwi
authors.forename: Ahmed
authors.initials: A
authors.lastname: Al Rumayan
authors.forename: Wafaa
authors.initials: W
authors.lastname: Eyaid
authors.forename: Waleed
authors.initials: W
authors.lastname: Al-Twaijri
mesh_terms: D000293:Adolescent; D000328:Adult; D001479:Basal Ganglia / Q000473:pathology; D001480:Basal Ganglia Diseases / Q000145:classification* / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D001710:Biotin / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D009154:Mutation; D011859:Radiography; D013831:Thiamine / Q000627:therapeutic use*; D014899:Wernicke Encephalopathy / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000503:physiopathology; D055815:Young Adult
chemical_list: D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human; D001710:Biotin; D013831:Thiamine