Impact of Early Evidence of Atherosclerotic Changes on Early Treatment in Children With Familial Hypercholesterolemia

Heterozygous familial hypercholesterolemia (HeFH) is the most common genetic metabolic disorder and is an important cause of premature atherosclerosis, particularly coronary artery disease. This is because of lifelong elevated plasma levels of low-density lipoprotein cholesterol (LDL-C) that result in deposition of LDL-C in tissues (xanthelasmas, xanthomas, and particularly tendinous xanthomas and corneal arcus), most importantly in arteries, forming atherosclerotic plaques. The affected subjects typically have LDL-C about at least double that of their unaffected siblings, and therefore clinically HeFH is most often recognized by finding very high LDL-C.1 It is well known that in patients with HeFH, high plasma LDL-C levels are present from birth, and because there are few other causes of increased LDL-C in childhood, such a finding is virtually diagnostic in children (unlike in adults), particularly if family history of premature cardiovascular disease is positive. In children with HeFH, clinical signs such as xanthomas and corneal arcus are not pathognomonic because they appear later in life. Because children in families where ≥1 member has FH are likely to be on a particular lipid-lowering diet and thus have lower LDL-C than expected, all children from such families should be checked by identification of the causative mutation in the LDL receptor, apolipoprotein B, or PCSK9 genes, which provides definitive diagnosis. Recently, a high-resolution melting method for mutation detection in patients with HeFH has been developed as a sensitive, rapid, and robust technique that could significantly reduce the time and cost of screening.2 This method was successfully used in screening of some populations that were previously underdiagnosed.3Article, see p 307Different screening strategies are currently suggested to identify children with FH. European guidelines are not recommending universal screening of children by either LDL-C measurement or some other approach.1 Although such a screening has often been …