Familial Combined Hypolipidemia

Excerpt

Clinical characteristics: Familial combined hypolipidemia is not associated with any pathologic signs or symptoms; diagnosis is suggested by low plasma concentrations of lipids. The lipid profile is one of hypocholesterolemia with low plasma low-density lipoprotein (LDL) cholesterol, low plasma high-density lipoprotein (HDL) cholesterol, low plasma triglycerides, and low plasma apolipoprotein (apo) B and apo A-I levels.

Diagnosis/testing: The molecular diagnosis of familial combined hypolipidemia is established in a proband with suggestive laboratory findings and biallelic pathogenic variants in ANGPTL3 identified by molecular genetic testing.

Management: No specific evaluation, management, or surveillance is required for individuals who have familial combined hypolipidemia; however, consultation with a medical geneticist, certified genetic counselor, or certified advanced genetic nurse to inform affected individuals and their families about the nature, mode of inheritance, and lack of specific clinical implications of familial combined hypolipidemia should be considered.

Genetic counseling: Familial combined hypolipidemia is inherited in an autosomal recessive manner. At conception, each sib of a person with FCH has a 25% chance of also having FCH, a 50% chance of being a heterozygous carrier, and a 25% chance of being unaffected and not a carrier. Heterozygotes for ANGPTL3 loss-of-function pathogenic variants have mildly reduced LDL cholesterol and triglyceride levels, and protection against atherosclerotic cardiovascular disease. Carrier testing for at-risk relatives is possible if the pathogenic ANGPTL3 pathogenic variants in the family are known. Prenatal and preimplantation genetic testing are also possible, but given the lack of clinical symptoms in most individuals who have FCH, this is not commonly pursued.