Abetalipoproteinemia (ABL) and familial hypobetalipoproteinemia (FHBL) are relatively uncommon inherited disorders of lipoprotein metabolism that cause low cholesterol levels.
Although persons whose low-density lipoprotein (LDL) cholesterol levels are moderately low (ie, individuals with FHBL) exhibit an enhanced tendency to develop fatty liver disease (FLD),
persons with a profound reduction of LDL cholesterol may have a decreased risk for heart disease.
ABL and FHBL are caused by genetic defects that encode for MTP or apoB molecules, respectively. ABL is caused by mutations in the MTP gene. FHBL is caused by a mutation in the APOB gene. Secondary hypobetalipoproteinemia may be associated with cancers, liver disease, severe malnutrition, and other wasting disorders.
ABL is a rare disease associated with a unique plasma lipoprotein profile in which LDL and very low-density lipoprotein (VLDL) are essentially absent. The disorder is characterized by fat malabsorption, spinocerebellar degeneration, acanthocytic red blood cells, and pigmented retinopathy. It is caused by a homozygous autosomal recessive mutation in the gene for microsomal triglyceride transfer protein (MTP). MTP mediates intracellular lipid transport in the intestine and liver and thus ensures the normal function of chylomicrons (CMs) in enterocytes and of VLDL in hepatocytes.
Affected infants may appear normal at birth, but by the first month of life, they develop steatorrhea, abdominal distention, and growth failure. Children develop retinitis pigmentosa and progressive ataxia, with death usually occurring by the third decade. Early diagnosis, high-dose vitamin E (tocopherol) therapy, and medium-chain fatty acid dietary supplementation may slow the progression of the neurologic abnormalities. Obligate heterozygotes (ie, parents of patients with ABL) have no symptoms and no evidence of reduced plasma lipid levels.
FHBL is also a rare disorder of apolipoprotein B (apoB) metabolism characterized by levels of plasma cholesterol and LDL cholesterol that are less than one-half normal in heterozygotes and are very low (< 50 mg/dL) in homozygotes. FHBL is caused by an autosomal, codominant mutation in the gene for apoB (APOB), which is carried on chromosome 2. This mutation results in a truncated form of apoB.
Homozygotes present with fat malabsorption and low plasma cholesterol levels at a young age. They develop progressive neurologic degenerative disease, retinitis pigmentosa, and acanthocytosis, similar to patients with ABL. Although heterozygotes are usually asymptomatic, they exhibit decreased LDL cholesterol and apoB levels and possibly have a decreased risk of atherosclerosis.
The nonfamilial forms of hypobetalipoproteinemia are secondary to a number of clinical states, such as occult malignancy, malnutrition, and chronic liver disease.