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.

Leber congenital amaurosis as an initial manifestation in a Chinese patient with thiamine‐responsive megaloblastic anemia syndrome

“…But we do not know if they will show up later. The similar situation, delayed diagnosis, has been reported in many previous cases (Kang et al, 2021; Odaman‐Al et al, 2019; Pichler et al, 2012; Pomahačová et al, 2017; Potter et al, 2017). This is mostly attributed to the low awareness of clinicians for this syndrome and treating TRMA as separate unrelated diseases over a long period of time.…”

“…Only few cases of such scenario, ocular manifestation was the first symptom, had been reported in the literature (Bergmann et al, 2009;Srikrupa et al, 2014). As we know, TRMA could present with ophthalmic features, such as retinitis pigmentosa, optic atrophy, cone-rod dystrophy, maculopathy, and Leber congenital amaurosis (Meire et al, 2000;Pomahac ˇová et al, 2017;Shaw-Smith et al, 2012;Srikrupa et al, 2014;Zhang et al, 2021). But these presentations are nonspecific that ophthalmologists tend to ignore them to link with systemic manifestations, especially when other symptoms SLC19A2 encodes the thiamine transporter 1 (THTR-1) that brings thiamine (vitamin B1) into cells.…”