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Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon
Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent epis...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437297/ https://www.ncbi.nlm.nih.gov/pubmed/36061186 http://dx.doi.org/10.3389/fgene.2022.961028 |
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author | Ayoub, Carine Azar, Yara Maddah, Dina Ghaleb, Youmna Elbitar, Sandy Abou-Khalil, Yara Jambart, Selim Varret, Mathilde Boileau, Catherine El Khoury, Petra Abifadel, Marianne |
author_facet | Ayoub, Carine Azar, Yara Maddah, Dina Ghaleb, Youmna Elbitar, Sandy Abou-Khalil, Yara Jambart, Selim Varret, Mathilde Boileau, Catherine El Khoury, Petra Abifadel, Marianne |
author_sort | Ayoub, Carine |
collection | PubMed |
description | Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia. |
format | Online Article Text |
id | pubmed-9437297 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-94372972022-09-03 Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon Ayoub, Carine Azar, Yara Maddah, Dina Ghaleb, Youmna Elbitar, Sandy Abou-Khalil, Yara Jambart, Selim Varret, Mathilde Boileau, Catherine El Khoury, Petra Abifadel, Marianne Front Genet Genetics Familial chylomicronemia syndrome is a rare autosomal recessive disorder of lipoprotein metabolism characterized by the presence of chylomicrons in fasting plasma and an important increase in plasma triglycerides (TG) levels that can exceed 22.58 mmol/l. The disease is associated with recurrent episodes of abdominal pain and pancreatitis, eruptive cutaneous xanthomatosis, lipemia retinalis, and hepatosplenomegaly. A consanguineous Syrian family who migrated to Lebanon was referred to our laboratory after perceiving familial chylomicronemia syndrome in two children. The LPL and PCSK9 genes were sequenced and plasma PCSK9 levels were measured. Sanger sequencing of the LPL gene revealed the presence of the p.(Val227Phe) pathogenic variant in exon 5 at the homozygous state in the two affected children, and at the heterozygous state in the other recruited family members. Interestingly, PCSK9 levels in homozygous carriers of the p.(Val227Phe) were ≈50% lower than those in heterozygous carriers of the variant (p-value = 0.13) and ranged between the 5th and the 7.5th percentile of PCSK9 levels in a sample of Lebanese children of approximately the same age group. Moreover, this is the first reported case of individuals carrying simultaneously an LPL pathogenic variant and PCSK9 variants, the L10 and L11 leucine insertion, which can lower and raise low-density lipoprotein cholesterol (LDL-C) levels respectively. TG levels fluctuated concomitantly between the two children, were especially high following the migration from a country to another, and were reduced under a low-fat diet. This case is crucial to raise public awareness on the risks of consanguineous marriages to decrease the emergence of inherited autosomal recessive diseases. It also highlights the importance of the early diagnosis and management of these diseases to prevent serious complications, such as recurrent pancreatitis in the case of familial hyperchylomicronemia. Frontiers Media S.A. 2022-08-19 /pmc/articles/PMC9437297/ /pubmed/36061186 http://dx.doi.org/10.3389/fgene.2022.961028 Text en Copyright © 2022 Ayoub, Azar, Maddah, Ghaleb, Elbitar, Abou-Khalil, Jambart, Varret, Boileau, El Khoury and Abifadel. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Genetics Ayoub, Carine Azar, Yara Maddah, Dina Ghaleb, Youmna Elbitar, Sandy Abou-Khalil, Yara Jambart, Selim Varret, Mathilde Boileau, Catherine El Khoury, Petra Abifadel, Marianne Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title | Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title_full | Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title_fullStr | Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title_full_unstemmed | Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title_short | Low circulating PCSK9 levels in LPL homozygous children with chylomicronemia syndrome in a syrian refugee family in Lebanon |
title_sort | low circulating pcsk9 levels in lpl homozygous children with chylomicronemia syndrome in a syrian refugee family in lebanon |
topic | Genetics |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9437297/ https://www.ncbi.nlm.nih.gov/pubmed/36061186 http://dx.doi.org/10.3389/fgene.2022.961028 |
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