Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is an extremely rare disorder of lipid metabolism caused by loss-of-function mutations in the LDL receptor adapter protein 1 (LDLRAP1) gene, which is characterised 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 nodules having 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 revealed 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 mutation. There was no known consanguinity in the family. She was commenced on the HMG-CoA reductase inhibitor, atorvastatin, to good effect, with a ~76% reduction in LDL-cholesterol at a dose of 50 mg per day. At six-month follow-up, there has been no obvious regression of the xanthomata, but no enlargement of cutaneous lesions or new xanthomata 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.

常染色体隐性遗传性高胆固醇血症（ARH; OMIM＃603813）是由LDL受体衔接蛋白1（LDLRAP1）基因功能丧失突变引起的脂质代谢异常罕见，其特征是严重的高胆固醇血症和早产风险增加动脉粥样硬化性心血管疾病。我们报告了一个11岁女孩的情况，该女孩在她的手肘和膝盖周围呈现多个无痛的淡黄色丘疹，持续两年。几位全科医生对她进行了复查，切除了一些结节，但没有做出明确的诊断。该儿童被转送到儿科服务处进一步评估和治疗皮肤病灶，这些皮肤病灶本质上似乎是黄瘤的。血脂谱显示严重的高胆固醇血症。对单基因高胆固醇血症基因组的下一代测序分析揭示了LDLRAP1中病原性移码突变c.71dupG，p.Gly25Argfs * 9的纯合性。她的父母和兄弟无症状，经过筛查，发现它们是LDLRAP1突变的杂合子携带者。这个家庭没有血缘关系。她开始服用HMG-CoA还原酶抑制剂阿托伐他汀，效果良好，每天50 mg的LDL-胆固醇减少约76％。在六个月的随访中，黄单胞菌无明显退化，但未出现皮肤病变扩大或新的黄单胞菌。总而言之，我们报告了一个儿童，该儿童表现出多处皮肤黄单胞菌病，并且通过在LDLRAP1中存在纯合的新型致病性移码变体而被证实患有ARH。