Lipid disorders and familial hypercholesterolaemia

The single fact that organises everything is the raised LDL-C from birth. A child with familial hypercholesterolaemia is not sick in front of you; the artery is sick, slowly, over decades. That is why the disease is missed, why it is under-treated, and why the evidence for treating it in childhood is so important. Lowering LDL-C early can normalise the carotid artery wall, and twenty years of follow-up shows no growth or safety penalty. ^{[2] [6]}

This page covers the recognition and management of paediatric lipid disorders, with familial hypercholesterolaemia at the centre: the LDL receptor pathway and its genetic defects, the LDL-C thresholds that flag the disease, selective and universal screening, the secondary causes that mimic it, the statin-first drug ladder, apheresis and the newer agents for homozygous disease, cascade screening of relatives, and the transition of the adolescent into adult care. ^[1]

Overview & Definition

Paediatric lipid disorders are abnormalities of circulating lipids — cholesterol, triglycerides and their lipoprotein carriers — found in childhood. Most are common and mild, driven by diet, adiposity and inactivity, and they raise triglycerides and lower HDL more than they raise LDL. The lipid disorder that carries the heaviest lifetime risk and the strongest case for early drug treatment is familial hypercholesterolaemia, an inherited defect of the LDL receptor pathway that produces a high LDL-C from birth. ^[1]

Familial hypercholesterolaemia is an autosomal dominant condition in nearly all cases, though a rare autosomal recessive form exists (LDLRAP1). A pathogenic variant in one allele is enough to roughly double the LDL-C, so a parent and half of siblings and children share the diagnosis. The three genetic causes are loss-of-function variants in the LDL receptor gene (LDLR) in most cases, a defective apolipoprotein B that cannot bind the receptor (APOB), and a gain-of-function PCSK9 that destroys receptors faster than they are made. ^[2]

The clinically useful distinction at the bedside is between heterozygous and homozygous disease. A child with one pathogenic allele has heterozygous FH and a roughly one in 250 birth prevalence; untreated, they develop atherosclerotic cardiovascular disease in the fourth to sixth decade. A child with two pathogenic alleles has homozygous FH and a prevalence near one in 160,000 to 300,000; untreated, they develop tendon xanthomas, aortic stenosis and coronary disease in the first or second decade. The distinction matters because it changes the urgency and the drug ladder. ^[3]

References12ShowHide

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