Skip to Main content Skip to Navigation
Journal articles

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.
Document type :
Journal articles
Complete list of metadata

https://hal.archives-ouvertes.fr/hal-02195269
Contributor : Laboratoire Carmen Connect in order to contact the contributor
Submitted on : Monday, July 26, 2021 - 6:10:29 PM
Last modification on : Thursday, July 29, 2021 - 4:05:41 AM

File

DiFilippo2018.pdf
Files produced by the author(s)

Licence


Distributed under a Creative Commons Attribution 4.0 International License

Identifiers

Citation

M. Di Filippo, M. Varret, V. Boehm, J. P. Rabes, L. Ferkdadji, et al.. Postprandial lipid absorption in seven heterozygous carriers of deleterious variants of MTTP in two abetalipoproteinemic families. Journal of clinical lipidology, Elsevier, 2019, 13 (1), pp.201-212. ⟨10.1016/j.jacl.2018.10.003⟩. ⟨hal-02195269⟩

Share

Metrics

Record views

619

Files downloads

53