Corneal Arcus, Xanthomas, and Finger Deformities in a Young Woman With Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia (HoFH) is a rare, autosomal dominant disorder characterized by severely elevated low-density lipoprotein cholesterol (LDL-C), leading to premature cardiovascular disease. Early diagnosis is critical but often delayed due to limited access to genetic testing, particularly in regions with high consanguinity.

A 23-year-old Persian woman, born to consanguineous parents, presented with tendon and cutaneous xanthomas, bilateral corneal arcus, and hand deformities resembling rheumatoid arthritis. Her medical history included childhood hypercholesterolemia, and her family history revealed premature myocardial infarction in her mother. Laboratory results showed markedly elevated LDL-C (509 mg/dL). Diagnosis was confirmed clinically using Dutch Lipid Clinic Network and Simon Broome criteria, as genetic testing was unavailable.

Initial therapy with rosuvastatin (40 mg) and ezetimibe (10 mg) failed to achieve LDL-C targets. Evolocumab (420 mg monthly) was added, resulting in an 82% reduction in LDL-C (from 509 to 89 mg/dL) and partial regression of xanthomas.

This case highlights the diagnostic challenges of HoFH in resource-limited settings and underscores the importance of clinical criteria when genetic testing is inaccessible. Aggressive lipid-lowering therapy, including PCSK9 inhibitors, is essential for managing HoFH and mitigating cardiovascular risk. Early recognition of physical signs (e.g., xanthomas and corneal arcus) and family screening are crucial for timely intervention.