Characterization of a Case of Pigmentary Retinopathy in Sanfilippo Syndrome Type IIIA Associated with Compound Heterozygous Mutations in the SGSH Gene

Ophthalmic Genet. 2016 Jun;37(2):217-27. doi: 10.3109/13816810.2015.1028647. Epub 2015 Sep 2.

Abstract

Purpose: To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel.

Methods: Heparan-N-sulfatidase enzyme function testing in skin fibroblasts and white blood cells and SGSH gene sequencing were obtained. Clinical office examinations, examinations under anesthesia, electroretinogram, spectral domain optical coherence tomography (SD-OCT), and fundus photography were performed over a 5-year period.

Results: Fundus examination revealed a progressive breadcrumb-like pigmentary retinopathy with perifoveal pigmentary involvement. SD-OCT showed loss of normal neuroretinal lamination and cystic macular changes responsive to treatment with carbonic anhydrase inhibitors. Electroretinography exhibited complex characteristics indicative of a generalized retinal rod > cone dysfunction with significant ON > OFF postreceptoral response compromise. Sequencing revealed compound heterozygous mutations in the SGSH gene, the novel c.88G > C (p.A30P) change and a second, previously reported one (c.734G > A, p.R245H).

Conclusions: We have identified ocular features of a patient with Sanfilippo syndrome type IIIA harboring a novel SGHS mutation that were not previously known to occur in this disease - namely, a progressive retinopathy with distinctive features, cystic macular changes responsive to carbonic anhydrase inhibitors, and complex electroretinographic abnormalities consistent with postreceptoral dysfunction. SD-OCT imaging revealed retinal lamination changes consistent with previously reported histologic studies. Both the SD-OCT and the electroretinogram changes appear attributable to intraretinal deposition of heparan sulfate.

Keywords: Electroretinogram; mucopolysaccharidosis; optical coherence tomography; pigmentary retinopathy; sanfilippo syndrome.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Electroretinography
  • Fibroblasts / enzymology
  • Humans
  • Hydrolases / genetics*
  • Male
  • Mucopolysaccharidosis III / diagnosis
  • Mucopolysaccharidosis III / enzymology
  • Mucopolysaccharidosis III / genetics*
  • Mutation*
  • Retinitis Pigmentosa / diagnosis
  • Retinitis Pigmentosa / enzymology
  • Retinitis Pigmentosa / genetics*
  • Skin / cytology
  • Sulfatases / metabolism
  • Tomography, Optical Coherence

Substances

  • Hydrolases
  • Sulfatases
  • heparan sulfate sulfatase
  • N-sulfoglucosamine sulfohydrolase