Late-onset Pseudoxanthoma Elasticum Associated with a Hypomorphic ABCC6 Variant

Area of Science:

• Ophthalmology
• Genetics
• Medical Research

Background:

• Pseudoxanthoma elasticum (PXE) is a rare genetic disorder characterized by ectopic calcification.
• Mutations in the ABCC6 gene are the primary cause of PXE.
• Late-onset forms of PXE may present with ocular manifestations mimicking other retinal diseases.

Observation:

• Three elderly patients presented with vision loss due to age-related macular degeneration (AMD)-like fundus changes.
• Characteristic PXE features, including angioid streaks and specific angiographic findings, prompted genetic investigation.
• Genetic testing revealed a hypomorphic ABCC6 variant (c.1171A>G) combined with a large deletion in all affected individuals.

Findings:

• The identified ABCC6 variant was supported as hypomorphic through molecular modeling.
• Patients exhibited ocular findings consistent with PXE but lacked significant skin or cardiovascular abnormalities.
• This suggests that ocular symptoms can be the sole manifestation of late-onset PXE.

Implications:

• Late-onset PXE expands the clinical spectrum of ABCC6-related disorders.
• Ocular findings suggestive of PXE can aid in diagnosis, even without typical skin or vascular signs.
• This study highlights the role of hypomorphic ABCC6 variants in the pathogenesis of PXE, particularly in its late-onset presentation.