Review of <i>SRD5A3</i> Disease-Causing Sequence Variants and Ocular Findings in Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case

Kousal, B.; Honzík, T.; Hansíková, H.; Ondrušková, N.; Čechová, A.; Tesařová, M.; Stránecký, V.; Meliška, M.; Michaelides, M.; Lišková, Petra

doi:10.14712/fb2019065030134

Folia Biologica > Archive > 2019, Vol. 65 > Issue 3 > Review of SRD5A3 Disease-Causing…

Fol. Biol. 2019, 65, 134-141

https://doi.org/10.14712/fb2019065030134

Review of SRD5A3 Disease-Causing Sequence Variants and Ocular Findings in Steroid 5α-Reductase Type 3 Congenital Disorder of Glycosylation, and a Detailed New Case

B. Kousal^1,2, T. Honzík², H. Hansíková², N. Ondrušková², A. Čechová², M. Tesařová², V. Stránecký², M. Meliška¹, M. Michaelides^3,4, Petra Lišková^1,2

¹Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
²Department of Paediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic
³Moorfields Eye Hospital NHS Foundation Trust, London, United Kingdom
⁴UCL Institute of Ophthalmology, University College London, London, United Kingdom

Received May 2019
Accepted June 2019

Steroid 5α-reductase type 3 congenital disorder of glycosylation (SRD5A3-CDG) is a severe metabolic disease manifesting as muscle hypotonia, developmental delay, cerebellar ataxia and ocular symptoms; typically, nystagmus and optic disc pallor. Recently, early onset retinal dystrophy has been reported as an additional feature. In this study, we summarize ocular phenotypes and SRD5A3 variants reported to be associated with SRD5A3-CDG. We also describe in detail the ophthalmic findings in a 12-year-old Czech child harbouring a novel homozygous variant, c.436G>A, p.(Glu146Lys) in SRD5A3. The patient was reviewed for congenital nystagmus and bilateral optic neuropathy diagnosed at 13 months of age. Examination by spectral domain optical coherence tomography and fundus autofluorescence imaging showed clear signs of retinal dystrophy not recognized until our investigation. Best corrected visual acuity was decreased to 0.15 and 0.16 in the right and left eye, respectively, with a myopic refractive error of –3.0 dioptre sphere (DS) / –2.5 dioptre cylinder (DC) in the right and –3.0 DS / –3.0 DC in the left eye. The proband also had optic head nerve drusen, which have not been previously observed in this syndrome.

Keywords

retinal dystrophy, SRD5A3-CDG, SRD5A3, novel variant.

Funding

This work was supported by grants AZV 16-31932A, RVO-VFN 64165 and SVV UK 260367/2017. Institutional support was provided by UNCE 204064 and Progres Q26/LF1. MM was supported by the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and UCL Institute of Ophthalmology, Fight for Sight (UK), Moorfields Eye Hospital Special Trustees, Moorfields Eye Charity, Retinitis Pigmentosa Fighting Blindness, and the Foundation Fighting Blindness (USA). This work was performed within the framework of ERN-EYE.