Thiamine-responsive megaloblastic anemia in two Ingush siblings with a homozygous SLC19A2 c.1223+1G>A variant

Abstract

Thiamine-responsive megaloblastic anemia (Rogers syndrome; OMIM #249270) is a rare autosomal recessive disorder caused by pathogenic variants in the SLC19A2 gene, which encodes the high-affinity thiamine transporter type 1. The disease is characterized by the classic triad of symptoms: megaloblastic anemia, non-autoimmune diabetes mellitus, and progressive sensorineural hearing loss. We report two sibling brothers of Ingush origin with genetically confirmed Rogers syndrome. In the older brother (3 years), the disease manifested with the classic triad in combination with cardiomyopathy, cardiac arrhythmias, and ophthalmologic pathology; the diagnosis was established in the setting of a fully developed clinical picture. In the younger brother (11 months), the disease was suspected based on a positive family history and early laboratory abnormalities (anemia, hyperglycemia, hyperlactatemia), which allowed initiation of thiamine replacement therapy prior to the onset of irreversible clinical symptoms. In both patients, whole genome sequencing identified a homozygous SLC19A2 variant c.1223+1GA. At follow-up 1.5 years later, the younger brother, while on continuous thiamine therapy, retained normal hearing and showed no evidence of anemia or diabetes mellitus.