Genetic Disorders of Lipoprotein Metabolism: Diagnosis and Management

Abstract

Disorders of lipoprotein metabolism are major contributors to cardiovascular disease (CVD). Dyslipidemia refers to elevated LDL-C levels, triglycerides, or remnant cholesterol, and decreased HDL-C. Most cases of CVD are multifactorial and/or polygenic in origin. However, (mono)genic causes can be suspected in individuals with early-onset CVD or with specific clinical hallmarks. The first step in the diagnostic workup of dyslipidemias is to exclude secondary dyslipidemias by obtaining a medical history and through biochemical testing. Specialized biochemical tests or genetic tests can often help in establishing a definite diagnosis. Treatment consists of lifestyle modifications, usually in combination with pharmacological agents such as statins. However, advances in gene technologies have enabled a rapid increase in the repertoire of available treatment options. This chapter provides an extensive overview of lipoprotein metabolism, followed by an overview of mono- and polygenic disorders of lipoprotein metabolism, including underlying causes, clinical and diagnostic characteristics, and available treatment options.