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
Abstrakt
Tiamine-responsive megaloblastc 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. 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 mutaions causing TRMA.