Thiamine-responsive megaloblastic anemia syndrome with novel compound heterozygous SLC19A2 mutations and thrombotic...

Thiamine-responsive megaloblastic anemia syndrome represents a rare autosomal recessive condition originating from mutations in the SLC19A2 gene. It is characterized by a classical triad of megaloblastic anemia, insulin-dependent diabetes mellitus, and sensorineural hearing loss. We present the case of a woman diagnosed with thiamine-responsive megaloblastic anemia, with no history of consanguinity, in whom genetic testing revealed novel SLC19A2 mutations and an unreported clinical manifestation.

This case describes an 18-year-old mestizo female patient who presented with a medical history of diabetes starting in infancy, bilateral sensorineural hearing loss, and megaloblastic anemia. The diagnosis of thiamine-responsive megaloblastic anemia was confirmed by genetic testing, which detected compound heterozygous mutations in the SLC19A2 gene that included a pathogenic frameshift mutation (c.620_624dup; p.Pro209Phefs*21) and a missense variant (c.170 T > C; p.Leu57Pro). The patient also experienced thrombotic events, including deep vein and mesenteric thrombosis, previously unreported findings in thiamine-responsive megaloblastic anemia. High-dose thiamine treatment resulted in improved hematologic and glycemic control.

This case broadens the genetic and clinical spectrum of thiamine-responsive megaloblastic anemia, highlighting the importance of genetic testing in young patients with the classic triad and showing that early thiamine therapy can markedly improve outcomes.