Aim:Thiamine-responsive megaloblastic anaemia syndrome(TRMA)is the association of diabetes mellitus,anaemia and deafness,due to mutations in SLC19A2,encoding a thiamine transporter protein.This is a unique monogenic f...Aim:Thiamine-responsive megaloblastic anaemia syndrome(TRMA)is the association of diabetes mellitus,anaemia and deafness,due to mutations in SLC19A2,encoding a thiamine transporter protein.This is a unique monogenic form of vitamin-dependent diabetes for which there is limited long-term data.We aimed to study genotype-phenotype relationships and long-term follow-up in our cohort.Methods:We have studied 13 patients from seven families and have follow-up data for a median of 9 y(2-30 y).Results:All patients originated from Kashmir or Punjab,and presented with non-immune,insulin deficient diabetes mellitus,sensorineural deafness and a variable anaemia in the first 5 y of life,the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow.The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d,but during puberty thiamine supplements became ineffective,and almost all patients require insulin therapy and regular blood transfusions in adulthood.All patients are homozygous for mutations in the SLC19A2 gene.We have identified a novel missense mutation(T158R)that was excluded in 100 control alleles.Conclusion:Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements;however,most patients become fully insulin dependent after puberty.A mutation screening strategy is feasible and likely to identify mutations in almost all cases.展开更多
文摘Aim:Thiamine-responsive megaloblastic anaemia syndrome(TRMA)is the association of diabetes mellitus,anaemia and deafness,due to mutations in SLC19A2,encoding a thiamine transporter protein.This is a unique monogenic form of vitamin-dependent diabetes for which there is limited long-term data.We aimed to study genotype-phenotype relationships and long-term follow-up in our cohort.Methods:We have studied 13 patients from seven families and have follow-up data for a median of 9 y(2-30 y).Results:All patients originated from Kashmir or Punjab,and presented with non-immune,insulin deficient diabetes mellitus,sensorineural deafness and a variable anaemia in the first 5 y of life,the anaemia progressing to megaloblastic and sideroblastic changes in the bone marrow.The anaemia and diabetes mellitus responded to oral thiamine hydrochloride 25 mg/d,but during puberty thiamine supplements became ineffective,and almost all patients require insulin therapy and regular blood transfusions in adulthood.All patients are homozygous for mutations in the SLC19A2 gene.We have identified a novel missense mutation(T158R)that was excluded in 100 control alleles.Conclusion:Diabetes in this syndrome is due to an insulin insufficiency that initially responds to thiamine supplements;however,most patients become fully insulin dependent after puberty.A mutation screening strategy is feasible and likely to identify mutations in almost all cases.
