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The article presents the first descriptions of observations in the Russian Federation, the difficult path to diagnosis in two young girls with diseases associated with mutations in the filamin A gene, characterized by damage to the central nervous system (periventricular nodular heterotopy), lungs (interstitial emphysematous lesion due to impaired growth), cardiovascular system (open arterial duct, high pulmonary hypertension, insufficiency of heart valves, large vessels). Clinical and anamnestic data, the results of laboratory and instrumental diagnostic methods, including molecular genetic ones, which allowed to identify unique, previously undescribed mutations, the characteristics of the course of the disease, the treatment being carried out, are presented.

Homozygous familial hypercholesterolemia is a severe genetic disorder characterized by extremely high levels of total cholesterol and low-density lipoprotein cholesterol (LDL-C), as well as by rapid atherosclerosis progression in various vascular territories. Objective examination of the affected patients often reveals multiple Achilles tendon xanthomas, xanthomas on the extensor surface of arms, knee joints, etc. The prevalence of such severe inherited hyperlipidemia in many populations is about 1 : 1 000 000, however, the family heterozygous type frequency increase leads to the decrease of this value and to the increase in the affected people number. The paper introduces case report for the patient V.I. aged 16 who was diagnosed with homozygous familial hypercholesterolemia at the age of 12. DNA testing revealed pathogenic mutations in the LDL receptor gene which confirmed the diagnosis. The paper reports the results of the discussed patient treatment using triple-drug combination lipid-lowering therapy with rosuvastatin (40 mg/day), ezetimibe (10 mg/day) and evolocumab (420 mg/day) in the last two years. The total cholesterol level decreased from 20.8 mmol/L (baseline) to 7.3–12.00 mmol/L, and the LDL-C level decreased from 19.9 mmol/L to 4.6–9.9 mmol/L due to therapy, the treatment was well tolerated. During the observation period, a rapid regression of xanthomas on the buttocks, knee and elbow joints, and Achilles tendon was achieved. A series of baseline instrumental tests (2013) revealed severe atherosclerosis of carotid arteries (maximum stenosis up to 50%), and first symptoms of aortic valve stenosis. Another examination in the hospital (2019) revealed slowing the progression of atherosclerosis in the carotid arteries and aorta, however, the arterial hypertension onset required additional prescription of a low dose of enalapril. Exercise testing and Holter ECG monitoring has yet identified no myocardial ischemia. Thus, the timely diagnosis together with long-term triple-drug intensive lipid-lowering therapy make it possible to slow down the atherosclerosis progression in the discussed rare and severe category of patients.