A Fatal Oversight: Severe Supravalvular Aortic Stenosis and Cutaneous Xanthomatosis in a Young Adult With Homozygous Familial Hypercholesterolemia

Homozygous familial hypercholesterolemia is a rare life-threatening genetic disorder of lipid metabolism characterized by exceptionally elevated low-density lipoprotein cholesterol, early-onset cutaneous xanthomatosis and accelerated atherosclerotic cardiovascular disease. This case report details a female patient in her twenties presenting with extensive childhood-onset tuberous and tendinous xanthomas, periorbital xanthelasmata and corneal arcus. She was diagnosed with severe dyslipidemia featuring a low-density lipoprotein cholesterol level of 612 milligrams per deciliter. Cardiovascular evaluation for progressive exertional dyspnea (NYHA class II) revealed severe supravalvular aortic stenosis and thickened aortic leaflets with a peak transvalvular velocity of 5.48 meters per second and a highly elevated mean transvalvular pressure gradient of 73 millimeters of mercury. Genetic sequencing identified a homozygous pathogenic missense mutation in the low-density lipoprotein receptor gene (c.530C>T; p.Ser177Leu). Despite available maximal lipid-lowering therapies (high-intensity statins, ezetimibe, bempedoic acid and inclisiran) the patient succumbed to early post-operative hemodynamic collapse during a planned complex aortoplasty and aortic valve replacement. This case underscores the necessity of early clinical recognition of cutaneous xanthomas, the rapid progression of atherogenic calcified supravalvular aortic stenosis the surgical risks associated with a calcified aorta and the urgent need for early receptor-independent pharmacological interventions.