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Background: Familial hypercholesterolemia (FH), mostly inherited as an autosomal dominant disease, is characterized by decreased low-density lipoprotein cholesterol (LDL-C) clearance from the plasma, due to mutation in the LDL receptor (LDL-R). Untreated or treatment resistant cases can have accelerated atherosclerosis leading to cardiovascular deaths. There are very few reports of liver transplant in children with refractory FH. Clinical Description: A 9-year-old girl was having tendinous xanthomas for last 18 months, which remained undiagnosed until she developed early onset acute coronary syndrome with triple-vessel disease. Treatment with statins was initiated for hypercholesterolemia which was detected only postcoronary artery bypass graft. The child was refractory to medical management. Management and Outcome: Genetic analysis revealed a compound heterozygous variant of FH (cHeFH) with a pathogenic mutation in LDL-R, with parents being heterozygotes. She underwent living donor liver transplantation (LT) from her heterozygote father. Posttransplantation, the lipid profiles improved markedly with gradual reduction in size of the xanthomas. Conclusion: FH, if undiagnosed and untreated, can cause serious complications as early as in the first decade. Simple cutaneous markers like tendon xanthomas should raise a suspicion of this condition and investigations should be carried out without further delay. LT, even from a heterozygous donor, can be rewarding in children with FH refractory to medical management.

Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH.

Familial hypercholesterolemia (FH) is a genetic disorder of lipoprotein metabolism resulting in elevated serum low-density lipoprotein (LDL) cholesterol levels leading to increased risk for premature cardiovascular diseases (CVDs). The diagnosis of this condition is based on clinical features, family history, and elevated LDL-cholesterol levels aided more recently by genetic testing. As the atherosclerotic burden is dependent on the degree and duration of exposure to raised LDL-cholesterol levels, early diagnosis and initiation of treatment is paramount. Statins are presently the mainstay in the management of these patients, although newer drugs, LDL apheresis, and other investigational therapies may play a role in certain subsets of FH, which are challenging to treat. Together these novel treatments have notably improved the prognosis of FH, especially that of the heterozygous patients. Despite these achievements, a majority of children fail to attain targeted lipid goals owing to persistent shortcomings in diagnosis, monitoring, and treatment. This review aims to highlight the screening, diagnosis, goals of therapy, and management options in patients with FH. [ABSTRACT FROM AUTHOR]

Heterozygous familial hypercholesterolemia (FH) is an inherited disorder of lipid metabolism, leading to severely elevated low-density lipoprotein-cholesterol levels and an increased risk of cardiovascular disease (CVD). Despite the monogenic cause of FH, CVD susceptibility varies considerably. Traditional risk factors, a specific low-density lipoprotein receptor mutation and modifier genes have been suggested to influence susceptibility to CVD. With the completion of the Human Genome Project and the availability of high throughput molecular methods, we expect that the creation of a genetic fingerprint of CVD risk in FH is feasible in the coming years. The challenge remains to link genetic data and clinical information to refine individualized approaches to CVD care in FH patients. [ABSTRACT FROM AUTHOR]

Abstract Background In the present study we assessed whether the presence of genetic mutations typical of familial hypercholesterolaemia (FH) was associated with greater atherosclerosis in the coronary vessels in patients with severe hypercholesterolaemia and a family history of early cardiovascular disease. Materials and methods Two hundred and thirty-five patients selected for having severe hypercholesterolaemia and a family history of cardiovascular disease were classified as FH (57 men and 38 women) or non-FH (84 men and 56 women) according to a genetic analysis of the LDL-R or ApoB genes. Coronary atherosclerosis was evaluated by performing a thoracic CT scan and exercise stress testing. Results Familial hypercholesterolaemia individuals had a significantly higher prevalence of coronary calcification than the non-FH patients from among both the men (OR = 3·90; 95% CI 1·86–8·19; P < 0·001) and the women (OR = 2·34; 95% CI 1·01–5·48; P = 0·05). In exercise stress testing, ECG abnormalities suggestive of cardiac ischaemia were found with a higher prevalence in the FH patients than the non-FH patients from among both the men (OR 6·15; 95% CI 2·16–17·5; P < 0·001) and the women (OR 4·76; 95% CI 0·91–24·6; P = 0·06). All differences were statistically significant after adjusting for age and cholesterol and for most classical risk factors that differed between the FH and non-FH groups. Conclusion Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher prevalence of coronary artery calcifications and a positive exercise stress test. These results suggest that despite a similar phenotype, patients carrying mutations suggestive of FH may have a greater cardiovascular risk than patients without these mutations. [ABSTRACT FROM AUTHOR]

Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, we assessed whether patients with mutations of low-density lipoprotein (LDL) receptor and apolipoprotein B genes related to familial hypercholesterolaemia (FH) have a different degree of atherosclerosis than those without such mutations. In our lipid clinics, 273 patients were selected on the basis of a severe hypercholesterolaemia (cholesterol above 95th percentile) and a family history of early cardiovascular disease. By molecular genetic test, 122 patients were classified as FH. Atherosclerosis was evaluated by the ultrasonographic measurement of intima-media thickness (IMT) in the carotid and femoral arteries. Despite the fact that non-FH individuals had a higher prevalence of obesity, hypertension, diabetes and hypertriglyceridaemia, FH individuals had significantly greater carotid and femoral IMT than non-FH patients: difference between carotid and femoral IMT, respectively, 0·19 mm (95% CI, 0·08–0·29; P < 0·001) and 0·20 mm (95% CI, 0·09–0·35; P = 0·001), respectively. These differences remained statistically significant after adjustment for the various risk factors as well as in sub-analysis restricted to the patients with LDL-cholesterol between 240 and 300 mg dL-1 (range with similar distribution in the two groups). When classified according to the severity of their mutations, FH individuals with null LDL receptor allele tended to have thicker carotid IMT than FH individuals carrying the LDL receptor-defective allele. Among patients with severe hypercholesterolaemia and a family history of early cardiovascular disease, the presence of a genetically ascertained FH is associated with a higher degree of atherosclerosis. This suggests that molecular genetic identification of FH may be helpful to evaluate better the coronary heart disease risk in these patients. [ABSTRACT FROM AUTHOR]