Pathogenic Variants in HGSNAT associated with Autosomal Recessive Retinitis Pigmentosa without Overt Sanfilippo...

Biallelic variants in the HGSNAT gene are associated with Sanfilippo syndrome, a rare lysosomal storage disorder caused by deficiency of heparan acetyl CoA glucosamine N-Acetyl-transferase enzyme(HGSNAT). The syndrome is characterized by multiple systemic findings, including progressive neurological and retinal degeneration. Retinitis pigmentosa due to HGSNAT gene variants are rarely reported without systemic manifestations.

Here we describe two patients with retinitis pigmentosa and reduced enzymatic activity. One of our patients also had hearing loss. We also present a review of the literature for cases of non-syndromic retinal dystrophy associated with HGSNAT variants in the discussion.

The first patient with retinitis pigmentosa and hearing loss has two variants of uncertain significance in the HGSNAT gene(p.Thr522Met and p.Cys79Arg). HGSNAT enzyme activity was 0.43nmol/17hr/mg(normal:5.8-45nmol/17hr/mg protein). Our second patient with isolated retinitis pigmentosa has two heterozygous pathogenic variants in HGSNAT (p.Arg124Trp and p.Ala615Thr). HGSNAT enzyme activity was 1.13nmol/17hr/mg(normal:5.8-45nmol/17hr/mg protein).

The retinal findings are consistent with HGSNAT-related disease. The first case is the second report of retinitis pigmentosa and hearing loss linked to HGSNAT-related disease. Both cases showed reduced HGSNAT enzyme activity in blood. Although more evidence is needed to definitively link adult-onset hearing loss to HGSNAT variants, it may be due to reduced enzyme activity.