Leber's congenital amaurosis as the retinal degenerative phenotype in thiamine responsive megaloblastic anemia: a case report.

BACKGROUND: Thiamine responsive megaloblastic anemia syndrome (TRMA), an autosomal recessive disorder is caused by mutations in the SLC19A2 gene which encodes for thiamine transporter 1 (THTR1) protein. TRMA presents with a triad of clinical features that includes diabetes mellitus, megaloblastic anemia and sensorineural hearing loss. Apart from the triad, reported ophthalmic features include cone rod dystrophy, optic atropy and retinitis pigmentosa.

MATERIALS AND METHODS: A female child presented with Leber's congenital amaurosis at 10 months of age, later diagnosed with hearing impairment at 1 year, diabetes mellitus and megaloblastic anemia at 3 and a half years of age and hence as a case of thiamine responsive megaloblastic anemia. Six exons of the candidate gene SLC19A2 were screened by PCR and direct sequencing. SIFT and PolyPhen analysis was done to predict the probable effect of the mutation.

RESULTS: Sequence analysis of the SLC19A2 coding region revealed a novel missense mutation in exon 2; c.314 G > A (p.G105E). Segregation analysis revealed parents heterozygous for the mutation and unaffected sib homozygous for wild type. SIFT and PolyPhen analyses predicted the mutation to be "damaging" (score-0.02) and "probably damaging" (score-0.994), respectively.

CONCLUSIONS: SLC19A2, the high-affinity thiamine transporter, is the only gene known to be associated with TRMA. Here we describe for the first time Leber's congenital amaurosis as the retinal phenotype and also report a novel point mutation in the SLC19A2 gene that co-segregated with the disease in a TRMA patient.