Lipoprotein disorders

Genest J. Lipoprotein disorders and cardiovascular risk. J Inherit Metab Dis 2003 26 267-287. 

Primary or genetic lipoprotein disorders are classified into six categories for the phenotypic description of dyslipidemia. The types and corresponding lipoprotein elevations include the following I (chylomicrons), Ha (LDL), lib (LDL + very low density lipoprotein, or VLDL), III (intermediate-density lipoprotein), IV (VLDL), and V (VLDL + chylomicrons). Secondary forms of hyperlipidemia also exist, and several drug classes may elevate lipid levels... 

Lipoprotein pattern types I, III, IV, and V are associated with hypertriglyceridemia, and these primary lipoprotein disorders should be excluded prior to implementing therapy. 

Lipoprotein disorders are detected by measuring lipids in serum after a 10-hour fast. Risk of heart disease increases with concentrations of the atherogenic lipoproteins, is inversely related to levels of HDL, and is modified by other risk factors (Table 35-1). Evidence from clinical trials suggests that LDL cholesterol levels of 60 mg/dL may be optimal for patients with coronary disease. Ideally, triglycerides should be below 120 mg/dL. Differentiation of the disorders requires identification of the lipoproteins involved (Table 35-2). Diagnosis of a primary disorder usually requires further clinical and genetic data as well as ruling out secondary hyperlipidemias (Table 35-3). 

The decision to use drug therapy for hyperlipidemia is based on the specific metabolic defect and its potential for causing atherosclerosis or pancreatitis. Suggested regimens for the principal lipoprotein disorders are presented in Table 35-2. 

The most dramatic advances, without doubt, have been in protein biochemistry. The genetic basis of lipoprotein disorders is being probed with the tools of molecular biology, proteins concerned with lipoprotein metabolism are being characterized with structural and physiological studies, lipoprotein receptors are being fully characterized, and competitive inhibitors of the rate-limiting enzyme for cholesterol synthesis, HMG-CoA reductase, have been produced. 

Source Especially from Schaefer EJ and Levy RI. Pathogenesis and management of lipoprotein disorders. N Engl J Med 312 1300-11310, 1985. 

Specific lipoprotein disorders (hyper- or hypolipoproteinaemia) are rare but there is increasing knowledge and awareness of the importance of apolipoproteins and their relevance to a variety of clinical disorders. 

F-2) Lipoprotein disorders. The most common causes of hyperlipidemia are diseases of lipid metabolism and excess cohol intake (alcohol is converted to acetyl CoA, which can convert to lipids). 

Lipoprotein disorders may also result from a variety of intestinal disorders that impede lipid absorption (such as certain inflammatory bowel diseases). Lipid disorders may also occur when there is triglyceride breakdown and shifting of triglyceride stores, as in the lipidemia that may accompany excess lipid breakdown in diabetes. 

Some of the lipoprotein disorders, apart from dietary-induced, that illustrate the above principles are (see also fig. 6.4) ... 

There are five primary inherited lipoprotein disorders which disturb lipid matabolism at the points indicated in Figure 25.1. These are ... 

Although several lipoproteins are considered to play a role in atherogenesis [VLDL, LDL and Lp(a)j, LDL cholesterol (LDL-C) is the primary target of therapy. The risk of CHD is inversely related to levels of HDL, because HDL is responsible for reverse cholesterol transport. Lipoprotein disorders can involve abnormalities in lipid metabolism (e.g., synthesis, transport, and catabolism). Attainment of a lipid profile must be made after a 9- to 12-hour fast. 

The clinical significance of lipids is primarily associated with coronary heart disease (CHD) and various lipoprotein disorders. 

Diagnosis of the Type III Lipoprotein Pattern. The ratio of VLDL cholesterol to plasma triglyceride, expressed in terms of mass, is 0.2 or lower in normal samples and in those from patients with lipoprotein disorders other than type III hyperlipidemia. In type III hyperlipoproteinemia, the ratio is 0.3 or higher because of the presence of p-VLDL, and the elevated ratio can persist even after treatment. 

J. J. Genest Jr., S. S. Martin-Munley, J. R. McNamara, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 85, 2025 (1992). 

Initial therapy for any lipoprotein disorder is therapeutic lifestyle changes with restricted intake of total and saturated fat and cholesterol and a modest increase in polyunsaturated fat intake, along with a program of regular exercise and weight reduction if needed. 

If pharmacologic therapy is insufficient after therapeutic lifestyle changes, lipid-lowering agents should be chosen based on the specific lipoprotein disorder presentation and the severity of the lipid abnormality. 

Rare forms of lipoprotein disorders may include hypobeta-lipoproteinemia, abetalipoproteinemia, Tangier disease, LCAT deficiency (fish-eye disease), cerebrotendinous xanthomatosis (CTX),... 

It is important to remember that lipoprotein pattern types I, III, IV, and V are associated with hypertriglyceridemia and that these primary lipoprotein disorders and underlying diseases should be excluded prior to implementing therapy (see Table 21-5). A positive family history of CHD is important in identifying patients at risk for prematme atherosclerosis. If a patient with CHD has elevated triglycerides, the associated abnormality is probably a contributing factor to CHD and should be treated. ... 

Lipoprotein disorders are some of the commonest metabolic diseases seen in clinical practice. They may present with their various sequelae which include ... 

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