Autosomal recessive hypercholesterolemia: Case report

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.