title: First 2 cases with thiamine-responsive megaloblastic anemia in the Czech Republic, a rare form of monogenic diabetes mellitus: a novel mutation in the thiamine transporter SLC19A2 gene-intron 1 mutation c.204+2T>G.
abstract: Thiamine-responsive megaloblastic anemia (TRMA) is a rare autosomal recessive disorder caused by mutations in the SLC19A2 gene. To date at least 43 mutations have been reported for the gene encoding a plasma membrane thiamine transporter protein (THTR-1). TRMA has been reported in less than 80 cases worldwide. Here, we illustrate 2 female patients with TRMA first diagnosed in the Czech Republic and in central Europe being confirmed by sequencing of the THTR-1 gene SLC19A2. Both subjects are compound heterozygotes with 3 different mutations in the SLC19A2 gene. In case 2, the SLC19A2 intron 1 mutation c.204+2T>G has never been reported before. TRMA subjects are at risk of diabetic ketoacidosis during intercurrent disease and arrythmias. Thiamine supplementation has prevented hematological disorders over a few years in both pediatric subjects, and improved glycaemic control of diabetes mellitus. Patient 1 was suffering from hearing loss and rod-cone dystrophy at the time of diagnosis, however, she was unresponsive to thiamine substitution. Our patient 2 developed the hearing loss despite the early thiamine substitution, however no visual disorder had developed. The novel mutation described here extends the list of SLC19A2 mutations causing TRMA.
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Renata
authors.initials: R
authors.lastname: Pomahačová
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Zamboryová
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Josef
authors.initials: J
authors.lastname: Sýkora
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Petra
authors.initials: P
authors.lastname: Paterová
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Karel
authors.initials: K
authors.lastname: Fiklík
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Tomáš
authors.initials: T
authors.lastname: Votava
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Zdeňka
authors.initials: Z
authors.lastname: Černá
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Petr
authors.initials: P
authors.lastname: Jehlička
authors.affiliation: Department of Paediatrics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Václav
authors.initials: V
authors.lastname: Lád
authors.affiliation: Institute of Medical Genetics, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Ivan
authors.initials: I
authors.lastname: Šubrt
authors.affiliation: Department of Neonatology, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Jiří
authors.initials: J
authors.lastname: Dort
authors.affiliation: Department of Neonatology, Faculty of Medicine in Pilsen, Charles University, Prague, Czech Republic.
authors.forename: Eva
authors.initials: E
authors.lastname: Dortová
mesh_terms: D000749:Anemia, Megaloblastic / Q000235:genetics*; D002675:Child, Preschool; D018153:Czech Republic; D003920:Diabetes Mellitus / Q000235:genetics*; D005260:Female; D006319:Hearing Loss, Sensorineural / Q000235:genetics*; D006801:Humans; D007223:Infant; D026901:Membrane Transport Proteins / Q000235:genetics*; D009154:Mutation; D013832:Thiamine Deficiency / Q000151:congenital* / Q000235:genetics
chemical_list: D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human
keywords: SLC19A2 gene; diabetes mellitus; diabetic ketoacidosis; sensorineural deafness; thiamine transporter; thiamine-responsive megaloblastic anemia