Introduction

Autosomal recessive hypercholesterolemia (ARH; OMIM #603813) is a very rare monogenic disorder affecting less than 1 in 1000,000 people and is characterized by very high levels of low-density lipoprotein cholesterol (LDL-C), leading to aggressive and premature atherosclerotic cardiovascular disease if left untreated. Lowering of LDL-C is the main target of the treatment. We report on a 29-year-old male patient born in nonconsanguineous Lithuanian family homo(hemi-)zygous for LDLRAP1 gene variant causing ARH. This variant is not present in population databases and, to our knowledge, has not been reported in scientific literature before.

Methods and results

The earliest clinical sign, noticed at the age of 5 years, was painful and enlarging nodules on Achilles tendons. At the age of 10 years, xanthomas of the metacarpal joint area on both hands emerged. The first lipid panel was performed at the age of 12 years. In accordance with Dutch Lipid Clinic Network diagnostic criteria for familial hypercholesterolemia (FH), definite FH (type IIA hyperlipoproteinemia) was diagnosed and the treatment with cholestyramine 4 grams per day was initiated. As the patient was 15 years old, direct adsorption of low-density lipoprotein apheresis was started and repeated monthly. At the age of 20 years, along with lipoprotein apheresis, 10 mg of rosuvastatin daily intake was prescribed. At the age of 28 years, the dose of rosuvastatin was increased to 40 mg per day, and 10 mg of ezetimibe daily intake was added. At the age of 28 years, homozygous LDLRAP1 gene variant NM_015627.2:c.488A>C, NP_056442.2:p.(Gln163Pro) causing autosomal recessive hypercholesterolemia was determined by genetic testing.

Conclusions

This case report implies that ARH, being an extremely rare disorder, is a severe disease. As there is limited routine testing, including genetic testing, patients suffering from both this disease and FH may remain undiagnosed. Cascade screening and genetic counseling differ for ARH as compared with FH, as the carrier of a pathogenic variant in the LDLRAP1 gene does not have marked total cholesterol and LDL-C elevations. However, genetic testing of the proband and their relatives is essential to evaluate the risk of development of FH and to provide prognosis as well as adequate, timely treatment. To improve the quality of life of patients with FH and prolong their life expectancy, national registries of FH and wider laboratory and genetic testing are undoubtedly necessary. A national FH screening program was set up in Lithuania, which helps to identify, monitor, and treat subjects with FH.

中文翻译：

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常染色体隐性遗传性高胆固醇血症：病例报告。

介绍

常染色体隐性遗传性高胆固醇血症（ARH; OMIM＃603813）是一种非常罕见的单基因疾病，仅影响1000,000人中的不到1人，其特征是低密度脂蛋白胆固醇（LDL-C）含量很高，导致侵袭性和过早的动脉粥样硬化如果不及时治疗，会导致心血管疾病。降低LDL-C是治疗的主要目标。我们报告了一名出生于立陶宛血缘不纯合子（hemi-）的不结盟立陶宛家庭的一名29岁男性患者，其引起LRHAP1基因变异导致ARH。在人口数据库中不存在该变体，据我们所知，以前在科学文献中也没有报道过。

方法与结果

最早的临床体征是在5岁时出现的，其疼痛和阿基里斯腱上的结节增大。在10岁时，双手出现了掌骨关节区域的黄瘤。首次脂质检查是在12岁时进行的。根据荷兰血脂临床网络对家族性高胆固醇血症（FH）的诊断标准，明确诊断为FH（IIA型高脂蛋白血症），并开始每天服用4克胆甾胺治疗。当患者15岁时，开始直接吸附低密度脂蛋白血液分离术，并每月重复一次。在20岁时，连同脂蛋白血液分离术一起，每天服用10毫克瑞舒伐他汀。在28岁时，瑞舒伐他汀的剂量增加到每天40 mg，并增加了每日摄入10 mg依泽替米贝。LDLRAP1基因变异NM_015627.2：c.488A> C，NP_056442.2：第（Gln163Pro）引起常染色体隐性遗传性高胆固醇血症是由遗传测试来确定。

结论

该病例报告表明，ARH是一种极为罕见的疾病，是一种严重的疾病。由于常规测试（包括基因测试）有限，因此患有此病和FH的患者可能仍无法诊断。与FH相比，对于ARH的级联筛查和遗传咨询有所不同，因为LDLRAP1基因中的致病变异体的携带者并没有明显的总胆固醇和LDL-C升高。但是，对先证者及其亲属进行基因检测对于评估FH发生的风险，提供预后以及适当及时的治疗至关重要。为了提高FH患者的生活质量并延长其预期寿命，毫无疑问，FH的国家注册机构以及更广泛的实验室和基因检测是必要的。在立陶宛建立了国家FH筛查计划，