Disorders of Lipoprotein Metabolism Discussion
Select a disease of lipoprotein metabolism. Provide a brief review of the disorder, including a molecular and biochemical characterization as well as essential clinical features. Be sure to include relevant therapeutic strategies for managing the condition.
Genetic disorders of lipoprotein metabolism
Deepak Bhatnagar, … Handrean Soran, in Clinical Molecular Medicine, 2020
14.5 Diagnosing genetic disorders of lipoprotein metabolism
Most patients with primary disorders of lipoprotein metabolism are diagnosed incidentally when clinicians come across very high serum lipid concentrations or those with premature CHD. When challenged by a persistently poor lifestyle and diet, the body is generally able to limit the rise in serum lipids. However, depending on background population serum lipid levels, a serum cholesterol levels higher than 7.0 or 7.5 mmol/L or moderate-to-severe hypertriglyceridemia should raise the suspicion of a genetic disorder of lipoprotein metabolism. There are also certain signs (Table 14.2)  that point to the presence of a genetic disorder. However, it is important to note that in some secondary hyperlipidemias, serum lipid concentrations may be as high as those seen in primary hyperlipidemia. The coexisting secondary disorder is generally clinically apparent in such cases (Table 14.3) but may require other tests to establish the secondary cause.
Disorders of Lipid Metabolism
Clay F. Semenkovich, … Ira J. Goldberg, in Williams Textbook of Endocrinology (Thirteenth Edition), 2016
Familial Dysbetalipoproteinemia (Type III Hyperlipoproteinemia)
Familial dysbetalipoproteinemia (formerly known as type III hyperlipoproteinemia) is an uncommon disorder of lipoprotein metabolism that is characterized by moderate to severe hypertriglyceridemia and hypercholesterolemia caused by the accumulation of cholesterol-rich remnant particles in the plasma. Premature peripheral vascular disease and coronary artery disease are common. The cause is mutations in the apoE gene that result in defective binding of apoE to lipoprotein receptors. The disorder is associated with the apoE2 isoform and in most instances is inherited as an autosomal recessive trait. Because the phenotypic expression of the disorder is limited to approximately 1% of the patients with the apoE2/E2 phenotype, other genetic or environmental factors must also be operative. The hyperlipidemia is caused by a defect in clearance of remnant lipoproteins whose liver uptake requires apoE interaction with the LDL receptor, LRP1, and HSPG (see earlier discussion). The remnants that accumulate have lost much of their triglyceride through LPL-mediated triglyceride hydrolysis and therefore are cholesterol rich. The predominant remnant particles, termed β-VLDL, can be identified by abnormal migration on gel electrophoresis or by abnormal lipid content.
Dysbetalipoproteinemia is usually diagnosed in adulthood and is rarely detected in persons younger than 20 years of age. The disorder is more common in men than in women. It is characterized by moderately severe elevations in plasma triglyceride and cholesterol levels; typically, these values both range from 300 to 400 mg/dL. Concentrations of HDL-C are normal. Xanthomas are present in more than half of affected subjects. Palmar xanthomas, which are planar xanthomas in the palmar creases (see Fig. 37-17F), are pathognomonic for this disorder. Tuberous or tuboeruptive xanthomas (see Fig. 37-17E) are also common but are less specific for this disorder. Tendon xanthomas and xanthelasma occur in some patients. Unlike FH, in which peripheral vascular disease is uncommon, premature peripheral vascular disease occurs in addition to premature coronary artery disease in patients with dysbetalipoproteinemia. Coexisting metabolic conditions that exacerbate the phenotype of dysbetalipoproteinemia, such as obesity, alcohol consumption, diabetes mellitus, and hypothyroidism, are often present.
In addition to homozygosity for the apoE2 isoform, some mutations in the apoE gene are known to lead to the dysbetalipoproteinemia phenotype in an autosomal dominant fashion. The phenotype manifests at an early age without exacerbating factors.