title: Thiamine responsive megaloblastic anemia: the puzzling phenotype.
abstract: BACKGROUND
  Thiamine responsive megaloblastic anemia (TRMA) is characterized by a triad of megaloblastic anemia, non-type 1 diabetes mellitus and sensorineural deafness. Other clinical findings have been described in few cases. The SLC19A2 gene on chromosome 1q 23.3 is implicated in all cases with TRMA. Our aim is to discuss the clinical manifestations of all Omani children diagnosed with TRMA and determine genotype-phenotype relationship.
  
  
  METHODS
  Clinical and laboratory data of all patients diagnosed in Oman were retrospectively collected. Mutation analysis of affected families was conducted using two Microsatellite markers. Genotyping was performed with fluorescent-labeled PCR primers. To define the deletion breakpoint region, PCR reactions were carried out using different primer pairs located at the introns 3 and 3'-untranslated region with Expand Long Template PCR kit.
  
  
  RESULTS
  A total of six children have been diagnosed with this syndrome. They were five females and one male. They all presented with sensorineural deafness at birth while the age of anemia presentation ranged between 6 weeks to 19 months. They all belong to same family with complex interfamilial marriages and presented with the typical triad. Of interest is the very rare presentation of one patient with Uhl cardiac anomaly (total absence of right ventricular myocardium with apposition of endocardium and pericardium) that has never been described before in patients with TRMA. All patients have a novel large deletion of 5,224 bp involving exons 4, 5, and 6 of SLC19A2.
  
  
  CONCLUSIONS
  TRMA is a disease of expanding phenotypic spectrum with poor genotype-phenotype correlation.
authors.affiliation: Department of Child Health, Sultan Qaboos University Hospital, Muscat, Oman.
authors.forename: Ismail
authors.initials: I
authors.lastname: Beshlawi
authors.forename: Shoaib
authors.initials: S
authors.lastname: Al Zadjali
authors.forename: Wafa
authors.initials: W
authors.lastname: Bashir
authors.forename: Mohamed
authors.initials: M
authors.lastname: Elshinawy
authors.forename: Abdulhakim
authors.initials: A
authors.lastname: Alrawas
authors.forename: Yasser
authors.initials: Y
authors.lastname: Wali
mesh_terms: D000749:Anemia, Megaloblastic / Q000188:drug therapy / Q000235:genetics*; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D010641:Phenotype; D012189:Retrospective Studies; D013831:Thiamine / Q000627:therapeutic use*
chemical_list: D013831:Thiamine
keywords: SLC19A2 gene; TRMA; Uhl anomaly