What is the role of genetics in the pathophysiology of familial hypobetalipoproteinemia (FHBL)?

Updated: Mar 06, 2018
  • Author: Vibhuti N Singh, MD, MPH, FACC, FSCAI; Chief Editor: George T Griffing, MD  more...
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Answer

FHBL is a rare autosomal dominant disorder of apoB metabolism. Most cases of known origin result from mutations in the APOB gene, involving 1 or both alleles. More than 30 mutations have been described. Most often, a mutation involving a 4–base–pair deletion in the APOB gene prevents translation of a full-length apoB-100 molecule, leading to the formation of truncated apoB molecules (apoB-37, with 1728 amino acids; apoB-46, with 2057 amino acids; or apoB-31, with 1425 amino acids). [4, 5, 14, 15, 16]

Metabolic turnover studies indicate that in some persons, these APOB gene mutations result in impaired synthesis of apoB-containing lipoproteins, and that in other patients, they cause increased catabolism of these proteins. Overall, beta-lipoprotein levels remain low.

Heterozygotes may have LDL cholesterol levels less than or equal to 50 mg/dL, but they often remain asymptomatic and have normal life spans. In the homozygous state, the absence of apoB leads to significant impairment of intestinal CM formation, which in turn leads to impaired absorption of fats and fat-soluble vitamins. Cholesterol absorption may also be impaired. Subsequent vitamin E malabsorption results in low tissue stores of vitamin E and leads to the development of degenerative neurologic disease. [5]


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