Abstract
Background: Familial hypobetalipoproteinemia (FHBL) and abetalipoproteinemia (ABL) are rare inherited forms of hypolipidemia. Their differential diagnosis is important for predicting of the prognosis and selecting appropriate therapy.
Materials and Methods: Genetic analysis was performed in two patients with primary hypocholesterolemia born from consanguineous parents. The oral fat tolerance test (OFTT) was performed in one patient with FHBL (apoB-87.77) and one with ABL as well as in four normal control subjects. After overnight fasting, blood samples were drawn. Serum lipoprotein and remnant-like particle (RLP) fractions were determined by HPLC analysis.
Results: Both patients with homozygous FHBL were asymptomatic probably because of preserved levels of fat-soluble vitamins, especially vitamin E. The patients with FHBL were homozygous because of novel apoB-83.52 and apoB-87.77 mutations, and although one of them (apoB-87.77) had fatty liver disease, microscopic findings suggesting nonalcoholic steatohepatitis were absent. Fasting apoB-48 and RLP-triglyceride levels in the patient with homozygous FHBL, which were similar to those in normal control subjects, increased after OFTT both in normal control subjects and the patient with FHBL but not in the patient with ABL, suggesting that the fat load administered was absorbed only in the patient with FHBL.
Conclusion: Although lipid levels in the patients with homozygous FHBL and ABL were comparable, fasting, postoral fat loading of apoB-48, as well as RLP-triglyceride levels, may help in the differential diagnosis of FHBL and ABL and provide a prompt diagnosis using genetic analysis in the future.
Competing interests: None declared
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Acknowledgment
We express sincere gratitude to Kazuko Honda (staff of Kanazawa University) for her outstanding technical assistance. The authors would like to thank Enago (www.enago.jp) for the English language review.
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Communicated by: Robert Steiner
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Take Home Message
Measuring apolipoprotein B-48 and remnant-like particle triglyceride levels before and after the oral fat tolerance test may help in the differential diagnosis of homozygous familial hypobetalipoproteinemia and abetalipoproteinemia.
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We hereby certify that this paper, which consists of unpublished original observations, is not under consideration for publication elsewhere. All coauthors have been involved in drafting and revising the article, and finally, this manuscript has been read and approved by all coauthors. Atsushi Nohara and Hiroshi Mabuchi have received research grants from MSD K.K., Sanofi K.K., Shionogi & Co., Ltd., Kowa Co., Ltd., Astellas Pharma Inc., AstraZeneca K.K., Keiaikai Medical Corp., and Biopharm of Japan Co. Masakazu Yamagishi has received research grants from Astellas Pharma Inc., Daiichi Sankyo Co., Ltd., and Ono Pharmaceutical Co., Ltd. Masa-aki Kawashiri, Hayato Tada, Marowa Hashimoto, Matsuo Taniyama, Takamitsu Nakano, Katsuyuki Nakajima, Takeshi Inoue, Mika Mori, Chiaki Nakanishi, Tetsuo Konno, Kenshi Hayashi, Akihiro Inazu, Junji Koizumi, Hirotaka Ishihara, Junji Kobayashi, and Tsutomu Hirano have no financial or other relations that could lead to a conflict of interest. All coauthors agreed to submit this article to the Journal of Inherited Metabolic Disease.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all participants for being included in the study. Additional informed consent was obtained from all patients for whom identifying information is included in this article.
Author Contributions
Masa-aki Kawashiri designed and performed all functions throughout the research and wrote the paper. Hayato Tada collected clinical data and performed the genetic analysis and fat-loading test. Marowa Hashimoto performed the genetic analysis. Takamitsu Nakano and Katsuyuki Nakajima performed the biochemical assay. Takeshi Inoue, Mika Mori, Chiaki Nakanishi, Tetsuo Konno, Kenshi Hayashi, and Atsushi Nohara collected the clinical data and performed the genetic analysis. Akihiro Inazu performed and supervised the genetic and biochemical analyses. Junji Koizumi collected the clinical data and supervised the genetic analysis. Hirotaka Ishihara collected the clinical data. Junji Kobayashi collected and supervised the clinical data and wrote the paper. Tsutomu Hirano collected and supervised the clinical data. Hiroshi Mabuchi and Masakazu Yamagishi supervised all aspects through the research period and wrote the paper.
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Kawashiri, Ma. et al. (2015). Extreme Contrast of Postprandial Remnant-Like Particles Formed in Abetalipoproteinemia and Homozygous Familial Hypobetalipoproteinemia. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 22. JIMD Reports, vol 22. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2015_415
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DOI: https://doi.org/10.1007/8904_2015_415
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