Identification of novel compound heterozygous variants in SLC19A2 and the genotype-phenotype associations in thiamine-responsive megaloblastic anemia

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

“…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.…”

“…TRMA is a complex rare syndrome and due to its rarity and broad spectrum of clinical symptoms which are nonspecific, so it can be easily misdiagnosed especially when the clinical presentations are incomplete. TRMA is progressive and most patients (84.1%) show the cardinal triad of the syndrome (Zhang et al, 2021). However, the different symptoms are mostly not congenital and often appear one after another over the long period of time (Bergmann et al, 2009; Zhang et al, 2021).…”

“…TRMA is progressive and most patients (84.1%) show the cardinal triad of the syndrome (Zhang et al, 2021). However, the different symptoms are mostly not congenital and often appear one after another over the long period of time (Bergmann et al, 2009; Zhang et al, 2021). This is also one of the important reasons why TRMA is often misdiagnosed or delayed diagnosed.…”

“…Generally, hearing loss occurred as the earliest sign of the triad of TRMA, with a median age of onset of 14.5 months. And the median age of onset of anemia and diabetes was 18 and 20 months, respectively (Zhang et al, 2021). However, vision impairment was the initial symptom in our patient.…”

“…TRMA has an extremely low incidence with less than 200 reported cases worldwide so far (Zhang et al, 2021), and mostly found in consanguineous families of Middle and Far Eastern origins. In addition to the typical symptom triad of TRMA, other manifestations have been observed, like retinal degeneration, optic atrophy, neurological deficit, developmental delay, and cardiac abnormalities (Habeb et al, 2018; Shaw‐Smith et al, 2012).…”