RESUMO
Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is an extremely rare disorder of lipid metabolism caused by loss-of-function variants in the LDL receptor adapter protein 1 (LDLRAP1) gene, which is characterized by severe hypercholesterolaemia and an increased risk of premature atherosclerotic cardiovascular disease. We report the case of an 11-year-old girl who presented with multiple painless yellowish papules around her elbows and knees of two-year duration. She had been reviewed by several general practitioners, with some of the papules having been excised, but without a specific diagnosis being made. The child was referred to a paediatric service for further evaluation and treatment of the cutaneous lesions, which appeared xanthomatous in nature. A lipid profile showed severe hypercholesterolaemia. Next generation sequencing analysis of a monogenic hypercholesterolaemia gene panel revealed homozygosity for a pathogenic frameshift mutation, c.71dupG, p.Gly25Argfs*9 in LDLRAP1. Her parents and brother, who were asymptomatic, were screened and found to be heterozygous carriers of the LDLRAP1 variant. There was no known consanguinity in the family. She was commenced on the HMG-CoA reductase inhibitor, atorvastatin, to good effect, with a â¼76% reduction in LDL-cholesterol at a dose of 50 mg per day. At six-month follow-up, there had been no obvious regression of the xanthomata, but importantly, no enlargement of, or the development of new papular lesions, have occurred. In summary, we report a child who presented with multiple cutaneous xanthomata and was confirmed to have ARH by the presence of a homozygous novel pathogenic frameshift variant in LDLRAP1.