Autosomal recessive hypercholesterolemia (ARH) is a rare monogenic disease, with an estimated prevalence of less than 1:1 000 000. It is characterized by extremely high levels of low-density lipoprotein cholesterol (LDL-C) and an increased risk of premature atherosclerotic cardiovascular disease.1 A detailed description of ARH is presented in Supplementary material, Autosomal recessive hypercholesterolemia. Here, we present a case of a 63-year-old woman homozygous for the LDLRAP1 gene, who is, to our best knowledge, the first patient in Poland with genetically proven ARH.

In the patient’s teenage years, nodules appeared in her Achilles tendons, making it difficult to put on shoes. Before the age of 30 years, she underwent a lipid profile screening, which revealed elevated levels of total cholesterol and LDL-C. She had been on various lipid-lowering therapies, but her cholesterol level remained very high. In October 2019, the patient reported to our outpatient clinic for treatment with PCSK9 inhibitors as part of a drug program. She is now 63 years old, and she is treated for arterial hypertension, chronic kidney disease, and paroxysmal atrial fibrillation. She has never smoked and denies alcohol consumption. She has been under the care of the Nephrology Clinic since around 2014 due to chronic kidney disease. In 2020, she underwent stenting of the right renal artery (Figure 1A and 1B), and a year later, the second procedure was performed due to stent restenosis. In the past, she had coronary angiography performed, which showed insignificant atherosclerotic lesions in the coronary arteries. Currently, the patient does not complain of stenocardia, denies shortness of breath, her exercise tolerance is good, and she does not report intermittent claudication.

Figure 1. A – angiographic image of the right renal artery before stenting; narrowing of the vessel in the ostium marked with an arrow; B – angiographic image after the stent implantation

Physical examination performed in October 2019 revealed bilateral xanthomas of the Achilles tendons (Supplementary material, Figure S1) and xanthelasma, as well as a systolic murmur in the projection of the aortic valve with radiation to both carotid arteries. Echocardiography revealed moderate aortic stenosis with a gradient of approximately 32/17 mm Hg and the aortic valve area of 1.1 cm2. According to the Dutch Lipid Clinic Network diagnostic criteria2 for familial hypercholesterolemia (FH), the patient was diagnosed with definite FH (a score of 14 points: 6 points for bilateral xanthomas in the Achilles tendons and 8 points for the LDL-C level of 11.3 mmol/l during treatment). Due to the unsatisfactory response to medical treatment, the patient underwent genetic testing, which revealed homozygous ARH [LDLRAP1 gene variant NM_015627.3:c.603dupC p.(Ser202LeufsTer19), rs781585299]. The exact results of laboratory tests with the accompanying lipid-lowering therapies and the patient’s family history, as well as a brief discussion of the available literature describing ARH are presented in Supplementary material.

ARH is a disease with a highly variable clinical course. However, patients with ARH are always at a significant cardiovascular risk, and identifying them by genetic testing is crucial to introduce aggressive lipid-lowering treatment as soon as possible. Identification and treatment of heterozygous ARH carriers are also extremely important because data on these patients and their risk profile are still scarce.