Cutaneous Xanthomas in a Young Boy – Markers of Homozygous Familial Hypercholesterolemia

Background: Homozygous familial hypercholesterolemia (HoFH) is a rare and potentially devastating, genetic cause of elevated lipid levels in children. Clinical Description: A 4-year-old boy presented with small, painless, nondischarging, nonpruritic, and slowly-enlarging nodules over both knees, for 6 months. Family history was unremarkable. Besides the nodules, rest of the physical examination was unremarkable, with a body mass index just above median. Multiple (maximum 1 cm), firm, nontender, yellowish lesions were present over both knees, consistent with xanthomatous deposits. Management and Outcome: Investigations were largely normal except markedly elevated levels of total cholesterol and low-density lipoprotein (LDL) at repeated instances. Family screening showed mother having elevated lipids. Echocardiography and ultrasound abdomen were normal. Genetic testing revealed pathogenic variant in the LDL receptor gene ( NM_000527.5 ) confirming HoFH type 1. The child was initiated on low-fat diet, atorvastatin with later addition of ezetimibe. Lipid levels showed decline by 6 weeks and child has been asymptomatic, under follow-up. Conclusion: Apparently innocuous, nontender, small cutaneous nodules need to be identified as cutaneous xanthomas. Biochemical and genetic evaluation of the index case as well as family screening may reveal HoFH, which has devastating cardiovascular prognosis. Timely initiation of aggressive combination lipid-lowering pharmacotherapy and dietary modifications may improve the outcomes.