Unraveling mucolipidosis type III gamma through whole genome sequencing in late-onset retinitis pigmentosa: a case report

Abstract

Background: We describe the case of a 47-year-old man referred to a retinal clinic and diagnosed with late-onset retinitis pigmentosa. Surprisingly, genetic testing revealed compound heterozygous pathogenic variants in GNPTG, leading to the diagnosis of the autosomal recessive lysosomal storage disorder mucolipidosis type III gamma. Mucolipidosis type III gamma is typically diagnosed during childhood due to symptoms relating to skeletal dysplasia. Retinal dystrophy is not a common phenotypic feature.

Case presentation: Ophthalmologic examination was consistent with a mild form of retinitis pigmentosa and included fundus photography, measurement of best-corrected visual acuity, optical coherence tomography, electroretinogram and visual field testing. Extraocular findings included joint restriction and pains from an early age leading to bilateral hip replacement by age 30, aortic insufficiency, and hypertension. Genetic analysis was performed by whole genome sequencing filtered for a gene panel of 325 genes associated with retinal disease. Two compound heterozygous pathogenic variants were identified in GNPTG, c.347_349del and c.607dup. The diagnosis of mucolipidosis type III gamma was confirmed biochemically by measurement of increased activities of specific lysosomal enzymes in plasma.

Conclusion: To our knowledge this is the first description of retinitis pigmentosa caused by compound heterozygous variants in GNPTG, providing further indications that late-onset retinal dystrophy is part of the phenotypic spectrum of mucolipidosis type III gamma.

Keywords: Case report; GNPTG; Inherited retinal dystrophy; Lysosomal disease; Mucolipidosis type III gamma; Retinitis pigmentosa; Whole genome sequencing.

Fig. 1

(A) Wide angle fundus photography, Optos. There is blunting of the foveal contour and scattered pigmentary changes in the middle periphery in the form of discrete bone-spicules and pigment clumping. (B) Wide angle fundus autofluorescence. The centre is well bounded. There is pathological patchy hypoautofluorescence in the middle periphery, and more homogenous hyperautofluorescence peripherally. (C) Optical coherence tomography. Extrafoveal scan at the right eye and foveal scan at the left eye. There is a mild epiretinal membrane with flattened foveal profile but without cystoid macular edema

Fig. 2

Threshold perimetry showing peripheral scotoma from the nasal site and well-preserved central sensibility