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Hypolipidemia is a decrease in plasma lipoprotein caused by primary (genetic) or secondary factors. It is usually asymptomatic and diagnosed incidentally on routine lipid screening. Treatment of secondary hypolipidemia involves treating underlying disorders. Treatment of primary hypolipidemia is often unnecessary, but patients with some genetic disorders require high-dose vitamin E and dietary supplementation of fats and other fat-soluble vitamins.
Hypolipidemia is defined as a total cholesterol (TC) < 120 mg/dL (< 3.1 mmol/L) or low-density lipoprotein (LDL) cholesterol < 50 mg/dL (< 1.3 mmol/L). Secondary causes are far more common than primary causes and include all of the following:
The unexpected finding of low cholesterol or low LDL cholesterol in a patient not taking a lipid-lowering drug should prompt a diagnostic evaluation, including measurements of AST, ALT, and thyroid-stimulating hormone; a negative evaluation suggests a possible primary cause.
There are 3 primary disorders in which single or multiple genetic mutations result in underproduction or increased clearance of LDL.
This autosomal recessive condition is caused by mutations in the gene for microsomal triglyceride (TG) transfer protein, a protein critical to chylomicron and very-low-density lipoprotein (VLDL) formation. Dietary fat cannot be absorbed, and lipoproteins in both metabolic pathways are virtually absent from serum; TC is typically < 45 mg/dL (< 1.16 mmol/L), TGs are < 20 mg/dL (< 0.23 mmol/L), and LDL is undetectable.
The condition is often first noticed in infants with fat malabsorption, steatorrhea, and failure to thrive. Intellectual disability may result. Because vitamin E is distributed to peripheral tissues via VLDL and LDL, most affected people eventually develop severe vitamin E deficiency. Symptoms and signs include visual changes from slow retinal degeneration, sensory neuropathy, posterior column signs, and cerebellar signs of dysmetria, ataxia, and spasticity, which can eventually lead to death. RBC acanthocytosis is a distinguishing feature on blood smear.
Diagnosis is made by the absence of apoprotein B (apo B) in plasma; intestinal biopsies show lack of microsomal transfer protein.
Treatment is with high doses (100 to 300 mg/kg once/day) of vitamin E with supplementation of dietary fat and other fat-soluble vitamins. The prognosis is poor.
Hypobetalipoproteinemia is an autosomal dominant or codominant condition caused by mutations in the gene coding for apo B. Heterozygous patients have truncated apo B, leading to rapid LDL clearance. Heterozygous patients manifest no symptoms or signs except for TC < 120 mg/dL (< 3.1 mmol/L) and LDL cholesterol < 80 mg/dL (< 2.1 mmol/L). TGs are normal. Homozygous patients have either shorter truncations, leading to lower lipid levels (TC < 80 mg/dL [< 2.1 mmol/L], LDL cholesterol < 20 mg/dL [< 0.52 mmol/L]), or absent apo B synthesis, leading to symptoms and signs of abetalipoproteinemia.
Diagnosis is by finding low levels of LDL cholesterol and apo B; hypobetalipoproteinemia and abetalipoproteinemia are distinguished from one another by family history. People who are heterozygous and people who are homozygous with low but detectable LDL cholesterol require no treatment. Treatment of people who are homozygous with no LDL is the same as for abetalipoproteinemia.
Loss of function mutations of PCSK9 are another cause of low LDL levels. There are no adverse consequences and no treatment,
Chylomicron retention disease is a very rare autosomal recessive condition caused by an unknown mutation leading to deficient apo B secretion from enterocytes. Chylomicron synthesis is absent, but VLDL synthesis remains intact. Affected infants have fat malabsorption, steatorrhea, and failure to thrive and may develop neurologic disorders similar to those in abetalipoproteinemia. Diagnosis is by intestinal biopsy of patients with low cholesterol levels and absence of postprandial chylomicrons. Treatment is supplementation of fat and fat-soluble vitamins.
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