Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families.

Abstract

BACKGROUND:

Abetalipoproteinemia, a recessive disease resulting from deleterious variants in MTTP (microsomal triglyceride transfer protein), is characterized by undetectable concentrations of apolipoprotein B, extremely low levels of low-density lipoprotein cholesterol in the plasma, and a total inability to export apolipoprotein B-containing lipoproteins from both the intestine and the liver.

OBJECTIVE:

To study lipid absorption after a fat load and liver function in 7 heterozygous relatives from 2 abetalipoproteinemic families, 1 previously unreported.

RESULTS:

Both patients are compound heterozygotes for p.(Arg540His) and either c.708_709del p.(His236Glnfs*11) or c.1344+3_1344+6del on the MTTP gene. The previously undescribed patient has been followed for 22 years with ultrastructure analyses of both the intestine and the liver. In these 2 families, 5 relatives were heterozygous for p.(Arg540His), 1 for p.(His236Glnfs*11) and 1 for c.1344+3_1344+6del. In 4 heterozygous relatives, the lipid absorption was normal independent of the MTTP variant. In contrast, in 3 of them, the increase in triglyceride levels after fat load was abnormal. These subjects were additionally heterozygous carriers of Asp2213 APOB in-frame deletion, near the cytidine mRNA editing site, which is essential for intestinal apoB48 production. Liver function appeared to be normal in all the heterozygotes except for one who exhibited liver steatosis for unexplained reasons.

CONCLUSION:

Our study suggests that a single copy of the MTTP gene may be sufficient for human normal lipid absorption, except when associated with an additional APOB gene alteration. The hepatic steatosis reported in 1 patient emphasizes the need for liver function tests in all heterozygotes until the level of risk is established.

• Authors: Mathilde Di Filippo, Mathilde Varret, Vanessa Boehm, Jean-Pierre Rabès, Latifa Ferkdadji, Laurent Abramowitz, Sabrina Dumont, Catherine Lenaerts, Catherine Boileau, Francisca Joly, Jacques Schmitz, Marie-Elisabeth Samson-Bouma, Dominique Bonnefont-Rousselot
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2019 Jan - Feb Vol. 13 Issue 1 Pg. 201-212 ISSN: 1933-2874 [Print] United States
• PMID: 30522860 (Publication Type: Journal Article)
• Copyright: Copyright © 2018 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Apolipoproteins B
• Carrier Proteins
• microsomal triglyceride transfer protein

Topics

• Abetalipoproteinemia (genetics)
• Adolescent
• Adult
• Apolipoproteins B (genetics, metabolism)
• Carrier Proteins (genetics)
• Child
• Child, Preschool
• Genotype
• Heterozygote
• Humans
• Infant
• Lipid Metabolism
• Liver (metabolism)
• Malabsorption Syndromes
• Male
• Middle Aged
• Pedigree
• Polymorphism, Genetic
• Postprandial Period
• Sequence Deletion (genetics)
• Young Adult