Characterization of a Case of Pigmentary Retinopathy in Sanfilippo Syndrome Type IIIA Associated with Compound Heterozygous Mutations in the SGSH Gene.
To report longitudinal phenotypic findings in a patient with Sanfilippo syndrome type IIIA, harboring SGSH mutations, one of which is novel.



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.



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).



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.
a Hamilton Eye Institute, Department of Ophthalmology and.
Justin
J
Wilkin
a Hamilton Eye Institute, Department of Ophthalmology and.
Natalie C
NC
Kerr
a Hamilton Eye Institute, Department of Ophthalmology and.
Kathryn W
KW
Byrd
b Medical Genetics Division, Department of Pediatrics , University of Tennessee Health Science Center , Memphis , TN , USA.
Jewell C
JC
Ward
a Hamilton Eye Institute, Department of Ophthalmology and.
Alessandro
A
Iannaccone
D000328:Adult; D004596:Electroretinography; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D006867:Hydrolases / Q000235:genetics*; D008297:Male; D009084:Mucopolysaccharidosis III / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D009154:Mutation; D012174:Retinitis Pigmentosa / Q000175:diagnosis / Q000201:enzymology / Q000235:genetics*; D012867:Skin / Q000166:cytology; D013429:Sulfatases / Q000378:metabolism; D041623:Tomography, Optical Coherence
D006867:Hydrolases; D013429:Sulfatases; C021346:heparan sulfate sulfatase; C022708:N-sulfoglucosamine sulfohydrolase
Electroretinogram; mucopolysaccharidosis; optical coherence tomography; pigmentary retinopathy; sanfilippo syndrome