Pigmentary retinopathy can indicate the presence of pathogenic LAMP2 variants even in somatic mosaic carriers with no additional signs of Danon disease.

Bohdan Kousal, Filip Majer, Hana Vlaskova, Lenka Dvorakova, Lenka Piherova, Martin Meliska, Hana Langrova, Tomas Palecek, Milos Kubanek, Alice Krebsova, Jiri Gurka, Veronika Stara, Michel Michaelides, Tomas Kalina, Jakub Sikora, Petra Liskova

Journal: Acta ophthalmologica 2021;99(1):61-68

PMID: 32533651

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Abstract

PURPOSE

Danon disease (DD) is a rare X-linked disorder caused by pathogenic variants in LAMP2. DD primarily manifests as a severe cardiomyopathy. An early diagnosis is crucial for patient survival. The aim of the study was to determine the usefulness of ocular examination for identification of DD.

METHODS

Detailed ocular examination in 10 patients with DD (3 males, 7 females) and a 45-year-old asymptomatic female somatic mosaic carrier of a LAMP2 disease-causing variant.

RESULTS

All patients with manifest cardiomyopathy had pigmentary retinopathy with altered autofluorescence and diffuse visual field loss. Best corrected visual acuity (BCVA) was decreased (<0.63) in 8 (40%) out of 20 eyes. The severity of retinal pathology increased with age, resulting in marked cone-rod involvement overtime. Spectral-domain optical coherence tomography in younger patients revealed focal loss of photoreceptors, disruption and deposition at the retinal pigment epithelium/Bruch's membrane layer (corresponding to areas of marked increased autofluorescence), and hyperreflective foci in the outer nuclear layer. Cystoid macular oedema was seen in one eye. In the asymptomatic female with somatic mosaicism, the BCVA was 1.0 bilaterally. An abnormal autofluorescence pattern in the left eye was present; while full-field electroretinography was normal.

CONCLUSIONS

Detailed ocular examination may represent a sensitive and quick screening tool for the identification of carriers of LAMP2 pathogenic variants, even in somatic mosaicism. Hence, further investigation should be undertaken in all patients with pigmentary retinal dystrophy as it may be a sign of a life-threatening disease.

Address: Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Department of Ophthalmology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Department of Ophthalmology, Faculty of Medicine in Hradec Kralove, Charles University and University Hospital Hradec Kralove, Hradec Kralove, Czech Republic.; 2nd Department of Medicine - Department of Cardiovascular Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Department of Cardiology, Institute for Clinical and Experimental Medicine, Prague, Czech Republic.; Department of Paediatrics, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.; Moorfields Eye Hospital NHS Foundation Trust, London, UK.; UCL Institute of Ophthalmology, University College London, London, UK.; Department of Paediatric Haematology and Oncology, Childhood Leukaemia Investigation Prague, Second Faculty of Medicine, Charles University and Motol University Hospital, Prague, Czech Republic.; Research Unit for Rare Diseases, Department of Pediatrics and Adolescent Medicine, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.; Institute of Pathology, First Faculty of Medicine, Charles University and General University Hospital in Prague, Prague, Czech Republic.

DOI: 10.1111/aos.14478

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MeSH Terms: Adult, Electroretinography, Female, Gene Expression Regulation, Glycogen Storage Disease Type IIb, Humans, Lysosomal-Associated Membrane Protein 2, Pedigree, RNA, Retinal Pigment Epithelium, Retinitis Pigmentosa, Tomography, Optical Coherence, Visual Acuity, Young Adult