Isolated Hypotaurinemia and Early-Onset Retinal Degeneration Associated with a Novel In-Frame SLC6A6 Variant of Uncertain Significance in a Consanguineous Family

Taurine is the most abundant free amino acid in the retina, and its uptake depends on the sodium- and chloride-dependent transporter TauT, encoded by SLC6A6. Biallelic SLC6A6 variants cause early-onset retinal dystrophy with severely reduced plasma taurine, at times accompanied by cardiomyopathy, and both the retinal and cardiac disease can stabilize with oral taurine, which makes early recognition important. We describe two brothers from a consanguineous Saudi family who presented in early childhood with poor vision, infantile nystagmus, hyperopia, marked peripheral retinal vascular attenuation, and loss of the ellipsoid zone on optical coherence tomography, with severely reduced scotopic and photopic full-field electroretinography in the older sibling. Whole-exome sequencing identified a homozygous in-frame deletion in SLC6A6 (NM_003043.5): c.85_129del, p.Arg29_Lys43del, which removes 15 conserved residues and was classified as a variant of uncertain significance. Both patients had isolated hypotaurinemia (12 and 7 µmol/L) against an otherwise normal amino acid profile, and echocardiography showed no cardiomyopathy. After two years of oral taurine at 100 mg/kg/day, plasma taurine normalized, the retinal findings remained stable, and cardiac evaluation stayed normal. This report adds the first small in-frame SLC6A6 deletion to the mutational spectrum, confirms isolated hypotaurinemia as a specific biochemical marker, and supports taurine supplementation together with cardiac surveillance.