Related Experiment Videos
Familial combined hyperlipidemia in children: clinical expression, metabolic defects, and management
J A Cortner1, P M Coates, C A Liacouras
1Lipid-Heart Research Center, Children's Hospital of Philadelphia, PA 19104.
Insights
Familial combined hyperlipidemia (FCHL) affects 1% of adults and causes premature coronary artery disease. Management includes diet, bile acid sequestrants, and potentially statins for adolescents with high LDL cholesterol.
Area of Science:
- Genetics and Cardiovascular Disease
- Metabolic Disorders
- Pediatric Cardiology
Background:
- Familial combined hyperlipidemia (FCHL) is a common inherited lipid disorder.
- FCHL accounts for 10% of premature coronary artery disease (CAD).
- FCHL is prevalent in families with childhood hyperlipidemia.
Purpose of the Study:
- To describe the genetic and metabolic basis of FCHL.
- To outline management strategies for FCHL in children and adolescents.
Main Methods:
- Review of existing literature on FCHL genetics and metabolism.
- Analysis of prevalence and inheritance patterns in affected families.
- Discussion of current and potential therapeutic interventions.
Main Results:
- FCHL is a dominant inherited condition affecting approximately 1% of adults.
- Metabolic defects include overproduction of very low-density lipoprotein (VLDL) apolipoprotein B or reduced lipoprotein lipase activity.
- A specific allele linked to apolipoprotein B levels predicts FCHL in many families.
Conclusions:
- Dietary modification is the first line of treatment for FCHL in children.
- Bile acid sequestrants can be used if LDL cholesterol remains high after age 10.
- Hydroxymethylglutaryl-coenzyme A reductase inhibitors may be considered for adolescents with persistent high LDL cholesterol.
Abstract:
Familial combined hyperlipidemia (FCHL) is a dominantly inherited hyperlipidemia that occurs in at least 1% of the adult population and is responsible for 10% of premature coronary artery disease. In families referred for evaluation because of primary hyperlipidemia in a child, FCHL is expressed three times more commonly than familial hypercholesterolemia and half of the siblings are affected. Several metabolic defects apparently are associated with the FCHL phenotype. Most commonly, excess production of very low density lipoprotein apolipoprotein B can be demonstrated. In other families, reduced lipoprotein lipase activity is associated. One allele at a locus influencing apolipoprotein B levels predicts FCHL in a large proportion of families ascertained through affected children. Whether this allele is responsible for the excess of very low density lipoprotein apolipoprotein B detected in metabolic studies has not been elucidated. Management of FCHL in children begins with dietary modification. A bile acid sequestrant may be considered as well if diet cannot reduce the plasma low-density lipoprotein cholesterol level to less than 4.13 mmol/L (160 mg/dl) after the age of 10 years. Although the hydroxymethylglutaryl-coenzyme A reductase inhibitors are not currently recommended for children younger than 19 years of age, we speculate that they will be increasingly utilized for the management of FCHL in teenage boys who continue to have low density lipoprotein cholesterol levels greater than 4.13 mmol/L (160 mg/dl) after dietary modification.