title: Thiamine transporter-2 deficiency: outcome and treatment monitoring.
abstract: BACKGROUND
  The clinical characteristics distinguishing treatable thiamine transporter-2 deficiency (ThTR2) due to SLC19A3 genetic defects from the other devastating causes of Leigh syndrome are sparse.
  
  
  METHODS
  We report the clinical follow-up after thiamine and biotin supplementation in four children with ThTR2 deficiency presenting with Leigh and biotin-thiamine-responsive basal ganglia disease phenotypes. We established whole-blood thiamine reference values in 106 non-neurological affected children and monitored thiamine levels in SLC19A3 patients after the initiation of treatment. We compared our results with those of 69 patients with ThTR2 deficiency after a review of the literature.
  
  
  RESULTS
  At diagnosis, the patients were aged 1 month to 17 years, and all of them showed signs of acute encephalopathy, generalized dystonia, and brain lesions affecting the dorsal striatum and medial thalami. One patient died of septicemia, while the remaining patients evidenced clinical and radiological improvements shortly after the initiation of thiamine. Upon follow-up, the patients received a combination of thiamine (10-40 mg/kg/day) and biotin (1-2 mg/kg/day) and remained stable with residual dystonia and speech difficulties. After establishing reference values for the different age groups, whole-blood thiamine quantification was a useful method for treatment monitoring.
  
  
  CONCLUSIONS
  ThTR2 deficiency is a reversible cause of acute dystonia and Leigh encephalopathy in the pediatric years. Brain lesions affecting the dorsal striatum and medial thalami may be useful in the differential diagnosis of other causes of Leigh syndrome. Further studies are needed to validate the therapeutic doses of thiamine and how to monitor them in these patients.
authors: Juan Darío
authors: JD
authors: Ortigoza-Escobar
authors: Mercedes
authors: M
authors: Serrano
authors: Marta
authors: M
authors: Molero
authors: Alfonso
authors: A
authors: Oyarzabal
authors: Mónica
authors: M
authors: Rebollo
authors: Jordi
authors: J
authors: Muchart
authors: Rafael
authors: R
authors: Artuch
authors: Pilar
authors: P
authors: Rodríguez-Pombo
authors: Department of Child Neurology, Sant Joan de Déu Hospital, University of Barcelona, Passeig Sant Joan de Déu, 2, Esplugues, Barcelona 08950, Spain. bperez@hsjdbcn.org.
authors: Belén
authors: B
authors: Pérez-Dueñas
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007888:Leigh Disease / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008991:Monitoring, Physiologic; D016896:Treatment Outcome
chemical_list: D026901:Membrane Transport Proteins; C492291:SLC19A3 protein, human