Fabry disease due to G171S GLA mutation: An atypical small nerve fiber sparing variant?

To describe the ocular manifestations and in vivo confocal microscopic findings in a patient carrying the recently described hemizygous G171S GLA gene mutation.

A 63-year-old Albanian male patient was evaluated for cataract surgery. Anamnesis showed pacemaker implantation in left ventricular hypertrophy, chronic kidney disease, family history for kidney transplantation, and late onset of sporadic acroparesthesias. Bilateral cornea verticillata, and increased tortuosity in conjunctival and retinal vessels were present. In vivo confocal microscopy revealed clusters of hyper-reflective corneal epithelial cells centripetally extending from the limbus. Interestingly, the nerve fiber number, density, and length in the corneal sub-basal nerve plexus were preserved. Alpha-galactosidase A activity was almost absent and hemizygous c.511G>A mutation (G171S - p.Gly171Ser) of the GLA gene was identified. The patient was referred for initiation of enzyme replacement therapy, and genetic counseling was recommended for at-risk family members.

This is the third reported case of Fabry disease due to GLA G171S mutation. All patients are of Albanian descent. Cornea verticillata and vascular anomalies remain common ocular manifestations, as well as cardiac and renal involvement. Confirming its pathogenicity, this mutation results in a "classic" Fabry disease phenotype, but it seems to be associated with a relative small nerve fiber sparing that may delay a correct diagnosis. The diagnosis of Fabry disease still remains challenging due to its clinical heterogeneity, but a thorough ophthalmological examination can promote early detection and, consequently, early initiation of enzyme replacement therapy.