(See also Overview of Lipid Metabolism Overview of Lipid Metabolism Lipids are fats that are either absorbed from food or synthesized by the liver. Triglycerides (TGs) and cholesterol contribute most to disease, although all lipids are physiologically important... read more .)
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).
Causes may be primary (genetic) or secondary. Secondary causes are far more common than primary causes and include all of the following:
Chronic infections (including hepatitis C infection Hepatitis C, Chronic Hepatitis C is a common cause of chronic hepatitis. It is often asymptomatic until manifestations of chronic liver disease occur. Diagnosis is confirmed by finding positive anti-HCV and positive... read more ) and other inflammatory states
Hematologic and other cancers
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 (aspartate aminotransferase), ALT (alanine aminotransferase), 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.
Chylomicron retention disease
Loss of function mutations of PCSK9 (proprotein convertase subtilisin-like/kexin type 9) are another cause of low LDL levels. There are no adverse consequences and no treatment,
Abetalipoproteinemia (Bassen-Kornzweig syndrome)
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; total cholesterol 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 Vitamin E Deficiency Dietary vitamin E deficiency is common in developing countries; deficiency among adults in developed countries is uncommon and usually due to fat malabsorption. The main symptoms are hemolytic... read more . Symptoms and signs include visual changes due to slow retinal degeneration, sensory neuropathy, posterior column signs of ataxia and paresthesias, and cerebellar signs of dysmetria, ataxia, and spasticity, which can eventually lead to death.
Diagnosis is made by the absence of apoprotein B (apo B) in plasma; intestinal biopsies show lack of microsomal transfer protein. Red blood cell acanthocytosis is a distinguishing feature on blood smear. Genetic testing can confirm the diagnosis.
Treatment is with high doses (100 to 300 mg/kg once a day) of vitamin E with supplementation of dietary fat and other fat-soluble vitamins. The prognosis is often poor.
Chylomicron retention disease (Anderson disease)
Chylomicron retention disease is a very rare autosomal recessive condition caused by deficient apo B secretion from enterocytes. Mutations in a gene encoding a protein important in transport of chylomicrons through enterocytes have been linked to this disorder.
Affected infants have fat malabsorption, steatorrhea, and failure to thrive and may develop neurologic disorders similar to those in abetalipoproteinemia Abetalipoproteinemia (Bassen-Kornzweig syndrome) 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... read more .
Diagnosis is by intestinal biopsy of patients with low cholesterol levels and absence of postprandial chylomicrons.
Treatment is supplementation of dietary fat and fat-soluble vitamins. Early treatment with high dose vitamin E may improve the prognosis.
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). Triglycerides are normal. Some patients may have hepatic steatosis Alcohol-Related Liver Disease Alcohol consumption is high in most Western countries. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 8.5% of US adults are estimated to... read more .
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 Abetalipoproteinemia (Bassen-Kornzweig syndrome) 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... read more .
Diagnosis is by finding low levels of LDL cholesterol and apo B on a serum lipid profile. 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 and includes vitamin E and supplementation of dietary fat and other fat-soluble vitamins. Prognosis is variable, but early diagnosis and strict adherence to treatment may delay disease progression.