Juvenile arcus cornealis and xanthomas in familial hypercholesterolemia

A 24-year-old gentleman, born of a nonconsanguineous marriage, presented with multiple swelling over his body. Family history revealed premature cardiac deaths in the paternal grandfather, father, and paternal uncle (30–40 years) and four sisters of the patient (16–20 years) all of whom had similar swellings. He had complete arcus cornealis (panel A—black arrowheads), xanthelasma palpebrarum (panel A—black arrows), multiple tuberous and tendinous xanthomas over the feet (panel B), sacrum (panel C—black arrows), extensor aspects of elbows, and knees. The patient also had planar xanthomas over the antecubital regions (panel D—black arrows). Investigations revealed markedly elevated serum total cholesterol (525 mg/dL), low-density lipoprotein-cholesterol (LDL-C; 475 mg/dL), and apolipoprotein B (306 mg/dL) but normal serum triglycerides (121 mg/dL). The patient was diagnosed with familial hypercholesterolemia. Clinical exome sequencing revealed compound heterozygous pathogenic variants (p.Cys184Ter and p.Trp666Ter) in the LDL receptor (LDLR) gene, confirming the diagnosis of familial hypercholesterolemia type 1. The patient was treated with rosuvastatin 20 mg per day, ezetimibe 10 mg per day, and cholecalciferol 60,000 IU per week for 8 weeks but with marginal reductions in serum total cholesterol (501 mg/dL) and LDL-C (458 mg/dL). The patient was offered other therapies with greater reduction in LDL-C such as proprotein convertase subtilisin/kexin type 9 inhibitors (21%–27%), lomitapide (34%–40%), LDL-apheresis (43%), and evinacumab (44%–47%). However, the patient deferred any of these therapies due to financial reasons.