Late-onset Pseudoxanthoma Elasticum Associated with a Hypomorphic ABCC6 Variant

• Published in: American journal of ophthalmology 2020-10, Vol.218, p.255-260
• Main Authors: Charbel Issa, Peter, Tysoe, Carolyn, Caswell, Richard
• Format: Article
• Language: English
• ISSN: 0002-9394; 1879-1891
• DOI: 10.1016/j.ajo.2020.05.009

To describe patients with late-onset pseudoxanthoma elasticum (PXE) associated with a likely hypomorphic ABCC6 variant. Retrospective observational case series. Clinical evaluation, multimodal retinal imaging, genetic testing, and molecular modeling. Three patients, in whom vision symptoms first arose at 80 years of age or later, showed age-related macular degeneration (AMD)-like fundus changes. However, features characteristic of PXE, including discrete angioid streaks and reduced fluorescence on late-phase indocyanine green angiography, prompted genetic testing which revealed the c.1171A>G variant in combination with a large deletion in the ABCC6 gene in each case. None of the patients had obvious skin changes or cardiovascular disease atypical for their age. Comparative molecular modeling supported the hypothesis that the c.1171A>GABCC6 variant acted as a hypomorphic variant. Late-onset PXE extends the spectrum of ectopic calcification disorders caused by mutations in ABCC6 and may clinically be limited to the eye, mimicking AMD. Patients may be identified based on specific ocular changes, whereas skin and cardiovascular changes may remain ambiguous. The study provides evidence for a role for hypomorphic ABCC6 variants in the pathogenesis of PXE.