The biochemical and genetic diagnosis of lipid disorders

To examine recent advances in our knowledge on the diagnosis of lipid disorders.

Fasting values above the 99th percentile for direct LDL-cholesterol (LDL-C), lipoprotein(a), and triglycerides are greater than 225 mg/dl, greater than 160 mg/dl, and greater than 500 mg/dl (>5.82, >394, and >5.65 mmol/l), respectively, whereas such values for plasma lathosterol, β-sitosterol, and cholestanol are greater than 8.0, 8.0, and 5.0 mg/l (>0.021, 0.019, and 0.013 mmol/l), respectively. Values below the first percentile for LDL-C are less than 40 mg/dl (<1.03 mmol/l) and for HDL-cholesterol (HDL-C) less than 25 mg/dl (<0.65 mmol/l) in men and less than 30 mg/dl (<0.78 mmol/l) in women, respectively. The above values can predispose to premature CVD, pancreatitis, neurologic disease, and kidney failure, and may be associated with monogenic lipid disorders. In the absence of secondary causes including diabetes or kidney, liver, or thyroid disease, consideration should be given to sequencing the following genes: ABCA1, ABCG5, ABCG8, APOA1, APOA5, APOB, APOC2, APOE, CETP, CYP27A1, GPIHBP1, LCAT, LDLR, LDLRAP1, LIPA, LIPC, LMF1, LPL, MTTP, PCSK9, SCARB1, and STAP1.

Recent data indicate that secondary causes and a wider range of conditions need to be considered in identifying the underlying causes of hypercholesterolemia, hypertriglyceridemia, hyperalphalipoproteinemia, hypobetalipoproteinemia, and HDL deficiency. Identifying such disorders allows for a more precise assessment of prognosis and the formulation of optimal therapy.