Pankaj Singhania,Pritam Biswas,Abhranil Dhar
Multiple Xanthoma Tuberosum in a Case of Familial Homozygous Hypercholesterolemia
xanthoma,familial,hypercholesterolemia,LDL
Multiple Xanthoma Tuberosum in a Case of Familial Homozygous Hypercholesterolemia

A 15-year-old, Indian, female child of a second-degree consanguineous marriage, presented with polymorphic yellowish-brown nodular cutaneous lesions over the dorsal aspect of both elbows, knees (Figure 1A) and buttocks (Figure 1B). These were suggestive of xanthoma tuberosum and were first noted at 4 years old. There were no spots over the eyelids, acanthosis, skin tags or tendon xanthomas. Arcus juvenilis was not noted. A bilateral carotid bruit was appreciated. Her father and mother also have hypercholesterolemia and were receiving atorvastatin. Her lipid profile showed total cholesterol: 790 mg/dL, LDL-C: 736 mg/dL, HDL-C: 34 mg/dL, VLDL-C: 124 mg/dL and triglyceride: 102 mg/dL. There was also increased carotid intima media thickness on doppler and severe aortic stenosis and normal Ejection fraction of 62% on echocardiogram. Genomic studies revealed homozygous mutation in both alleles of the LDL-R gene, associated with autosomal dominant Familial Hypercholesterolemia. The 737-position arginine (R) was also changed. This change, previously reported by Mozas et al., in a Spanish patient, was not present in genomic databases reviewed as of writing. The patient was subsequently diagnosed with Homozygous Familial Hypercholesterolemia using the Simon Broome Register criteria. Diet modification, atorvastatin and ezetimibe were started, followed by subcutaneous evolocumab. After 6-8 weeks of therapy with atorvastatin, ezetimibe and evolocumab, her cholesterol levels were markedly reduced by 82 and 89%, respectively. However, the patient discontinued the use of evolocumab due to financial constraints. Homozygous familial hypercholesterolemia is a disorder of lipoprotein metabolism from mutations in the low-density lipoprotein receptor (LDLR) gene, which manifests as xanthomas. Guidelines for dyslipidaemia recommend high intensity statin treatment at 6-10 years of age, with healthy lifestyle measures and use of PCSK-9 inhibitors for children with homozygous familial hypercholesterolemia. Goals for children >10 years of age are LDL-C <3.5 mmol/l (135 mg/dL) or at least a 50% reduction from the baseline.