Current Approach to the Diagnosis and Treatment of Heterozygote and Homozygous FH Children and Adolescents

Abstract

Purpose of Review To elucidate the current approach of care in pediatric patients with familial hypercholesterolemia (FH). We sought an answer to the question whether the advances and major changes in lipid management are relevant and apply to children and adolescents. Recent Findings Latest research findings clearly demonstrate that lowering cholesterol levels at a young age prevents vascular atherosclerotic changes and decreases cardiovascular events in adulthood and emphasizes the importance of early detection and intervention in the pediatric FH patients group. Summary FH is a common genetic disease caused by mutations in genes associated with the metabolism of low-density lipoproteins (LDL). The hallmark of FH is elevated LDL cholesterol (LDL-C) levels from birth and premature atherosclerotic cardiovascular disease (ASCVD). Often FH is either undiagnosed or diagnosed with a considerable delay, leading to vascular atherosclerotic changes and cardiovascular disease. Prompt identification of FH subjects is essential, to initiate early preventive measures. Safe and efficient pharmacological agents are approved for use in children and adolescents. Statins are the first line of therapy, in combination of ezetimibe. Unfortunately, these drugs do not warrant the achievement of therapeutic target, especially in HoFH patient. In the latter, lipoprotein apheresis (LA), which has been shown to be safe and effective, is strongly recommended. Finally, the new drugs still under study will allow a multimodal customized treatment. Lowering cholesterol levels at a young age hinders vascular atherosclerotic changes decreasing cardiovascular events in adulthood. Therefore, early detection, diagnosis, and intervention in FH patients are priority objectives.

Developing a Hybrid Risk Assessment Tool for Familial Hypercholesterolemia: A Machine Learning Study of Chinese Arteriosclerotic Cardiovascular Disease Patients

“…Homozygous FH is an orphan disease, with a low prevalence of 1 in 300,000 individuals ( 47 ). Homozygous FH patients have very high LDL-C levels from birth, accelerated arterial stenosis and atherosclerosis, and premature death in their juvenile stage ( 48 ) due to myocardial infarction/acute coronary insufficiency. Our tools were built based on patients older than 18 years.…”

Saudi Familial Hypercholesterolemia Patients With Rare LDLR Stop Gain Variant Showed Variable Clinical Phenotype and Resistance to Multiple Drug Regimen

“…Early intervention to control the high LDL-C levels is clearly beneficial in reducing the cardiovascular events among young FH patients (45). The genetic testing of LDLR, c.2027delG variant in extended family members of both family A and B could potentially offer an advantage of early identification of FH cases, planning lifelong lipid lowering therapy, genetic counseling, and prenatal diagnosis (46).…”

Advancements in the Treatment of Homozygous Familial Hypercholesterolemia

“…By altering LDLR activity and reducing LDL-C uptake from circulation, these genetic changes result in a marked increase in circulating LDL-C level starting at birth. After ruling out secondary factors that may influence hypercholesterolemia, an LDL-C level ＞400 mg/dL (＞10 mmol/L), together with a positive family history inhibitor of the Niemann-Pick C1-Like 1 (NPC1L1) protein, inhibits cholesterol absorption and adds an additional 10%-15% reduction in LDL-C levels 15,16) and should be added to statin therapy as a second LDL-C-lowering agent. Statins, alone and in combination with ezetimibe, have been shown to reduce CVD mortality in patients with HoFH 17) , including in the pediatric population 10) .…”