TY - JOUR
AU - Plutzky,, Jorge
AB - In this case of hypobetalipoproteinemia (HBL), differential diagnoses for genetic and secondary HBL are provided. Several additional issues can be noted. This patient also had an IgA paraproteinemia, which can influence cholesterol concentrations. Monoclonal paraproteinemia can hinder lipoprotein clearance, thereby increasing circulating cholesterol while artifactually lowering cholesterol measurements (1). This patient's cholesterol concentrations were lower than those typically observed with heterozygous genetic HBL, raising the question of paraprotein interference or another unidentified heterozygous mutation influencing apolipoprotein B (apo B) concentrations. Perhaps another familial variant was in play in the death of the proband's son at age 21 years. Familial hypocholesterolemia has received recent attention with the identification of mutations in the ANGPTL32 (angiopoietin-like 3) and PCSK9 (proprotein convertase subtilisin/kexin type 9) genes as novel causes of low cholesterol concentrations (2). Like HBL-associated apo B variants, ANGPTL3 and PCSK9 mutations appear well tolerated and potentially atheroprotective, features that are generating therapeutic interest in these targets. Similarly, inhibiting APOB transcription via the use of antisense oligonucleotides is in late-stage therapeutic development. Ongoing attempts to lower apo B concentrations despite the success of statins and other cholesterol-lowering medications (e.g., ezetimibe, bile acid sequestrants, niacin) reflect many clinical issues: statin intolerance, high baseline cholesterol concentrations, the lowering of LDL goals, and the increasing identification of familial hypercholesterolemia and its treatment challenges. 2 Human genes ANGPTL3 angiopoietin-like 3 PCSK9 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. References 1. Tsai LY , Tsai SM, Lee SC, Liu SF. Falsely low LDL-cholesterol concentrations and artifactual undetectable HDL-cholesterol measured by direct methods in a patient with monoclonal paraprotein . Clin Chim Acta 2005 ; 358 : 192 – 5 . Google Scholar Crossref Search ADS PubMed WorldCat 2. Calandra S , Tarugi P, Speedy HE, Dean AF, Bertolini S, Shoulders CC. Mechanisms and genetic determinants regulating sterol absorption, circulating LDL levels, and sterol elimination: implications for classification and disease risk . J Lipid Res 2011 ; 52 : 1885 – 926 . Google Scholar Crossref Search ADS PubMed WorldCat © 2012 The American Association for Clinical Chemistry This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)
TI - Commentary
JO - Clinical Chemistry
DO - 10.1373/clinchem.2012.182139
DA - 2012-05-01
UR - https://www.deepdyve.com/lp/oxford-university-press/commentary-zljE8SqEEh
SP - 829
VL - 58
IS - 5
DP - DeepDyve
ER -