ESPE Abstracts

Background: Familial hypercholesterolemia (FH) is the most common monogenic disorder causing premature atherosclerotic cardiovascular disease (ACVD), particularly early coronary artery disease. Homozygous FH (HoFH) is rare and can be clinically silent in most cases, contributing to delay in diagnosis till the occurrence of potentially fatal cardiovascular events (CVE). Patients with HoFH can be highly resistant to standard pharmacological therapies, and treatment management can be very challenging. We describe the management of two HoFH pediatric patients.

Case Report: Patient 1 (male, 8 years) came to our attention for cutaneous xanthomas detected during dermatological examination. Baseline lipid profile: total cholesterol (TC) 539 mg/dl, low-density lipoprotein cholesterol (LDL-C) 452 mg/dl. Positive family history of hypercholesterolemia in both parents and maternal grandparents. Clinical examination: normal except for 3 skin xanthomas. Genetic examination identified two different mutations on LDL-R (c.1048C>T and c.1775G>A), inherited from the father and the mother, respectively. Cardiovascular tests were negative. Dietary recommendations, physical activity and statin therapy were suggested, gradually adding Ezetimibe and Evolocumab. At the last lipid assessment, with the maximum dose possible for the child, LDL-C was not on target (160 mg/dl, -65% from baseline) and he is going to start therapy with Evinacumab in the next month. Patient 2 (male, 5 months old) with positive family history of hypercholesterolemia in both parents and older sisters. Due to family history, screening examinations were performed: TC 884 mg/dL, LDL-C 692 mg/dL, TG 459 mg/dL. Normal clinical exam. Genetic analysis revealed LDLR homozygous mutation (c.1646G>A), inherited from the parents, both heterozygous. Cardiovascular tests were negative. Considering the lack of response to the high-dose treatment with statin and Ezetimibe in his sister and the limits of lipoprotein apheresis in children of such young age, we decided on the compassionate use of Evinacumab which was started when he was 13 months old. At the last evaluation (after 10 infusions), LDL-C decreased from baseline by 82% and TG by 88%.

Conclusion: FH is often underdiagnosed and undertreated, particularly in children, since physical signs are rarely observed. Lipid profile screening would guarantee early identification of these patients, and genetic analysis should be performed when family history or clinical data are very suggestive. Treatment options in the pediatric population are limited but the efficacy of newly emerging drugs, like Evinacumab, with tolerability and minimal invasiveness, represents an excellent opportunity for increasing patients’life expectancy and improving their quality of life.