This case study nicely illustrates the typical problems encountered in trying to understand the underlying cause for a patient with an abnormal lipid phenotype. As was done in this case, it is very important to try to get as much information as possible about the lipid values of other family members. Patients who are homozygous for familial hypobetalipoproteinemia (FHBL) will usually have one parent with a low apolipoprotein B (apo B) value. In contrast, parents of patients with abetalipoproteinemia usually have normal apo B concentrations, because it is an autosomal recessive disorder. In this case, the negative history of malabsorption and the detection of a single apo B mutation are consistent with heterozygous FHBL. These patients frequently do have apo B concentrations less than half of normal, which is probably a consequence of the decreased apo B pool size and improved LDL clearance, but, unlike in this case, apo B is still usually detectable. It was not clear from this report how the APOB gene was sequenced. If just the exons were examined, the patient perhaps has a mutation in the promoter or intron of the other allele that leads to decreased expression. Because the discovered apo B mutation was downstream from the site for apo B editing, apo B-48 synthesis for chylomicron production may have been preserved, thus preventing malabsorption. The patient could also have a mutation in another gene that affects apo B metabolism, such as PCSK92 (proprotein convertase subtilisin/kexin type 9), which can lower apo B concentrations by modulating LDL receptor activity (1). Another possibility is that the paraprotein produced by the monoclonal gammopathy of undetermined significance could be involved. Autoantibodies against the protein or lipid components of lipoproteins can lower LDL and HDL; such effects can be examined with mixing studies (2). Nevertheless, this is a nice case report of a rare disease that is important to recognize so that therapy with high-dose vitamins A and E can be started. Such treatment can prevent the serious neurologic and vision problems that homozygous FHBL and abetalipoproteinemia patients develop because of the decreased packing and transport of fat-soluble vitamins on apo B–containing lipoproteins.
↵2 Human genes:
- proprotein convertase subtilisin/kexin type 9.
Author Contributions: All authors confirmed they have contributed to the intellectual content of this paper and have met the following 3 requirements: (a) significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (b) drafting or revising the article for intellectual content; and (c) final approval of the published article.
Authors' Disclosures or Potential Conflicts of Interest: No authors declared any potential conflicts of interest.
- Received for publication February 16, 2012.
- Accepted for publication February 21, 2012.
- © 2012 The American Association for Clinical Chemistry