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Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families
BACKGROUND: In metabolic stress, the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) enzyme is involved in energy production through the gluconeogenesis pathway. PEPCK-C deficiency is a rare childhood-onset autosomal recessive metabolic disease caused by PCK1 genetic defects. Previous studies...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625263/ https://www.ncbi.nlm.nih.gov/pubmed/37924129 http://dx.doi.org/10.1186/s13023-023-02946-5 |
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author | Al Busaidi, Marwa Mohamed, Feda E. Al-Ajmi, Eiman Al Hashmi, Nadia Al-Thihli, Khalid Al Futaisi, Amna Al Mamari, Watfa Al-Murshedi, Fathiya Al-Jasmi, Fatma |
author_facet | Al Busaidi, Marwa Mohamed, Feda E. Al-Ajmi, Eiman Al Hashmi, Nadia Al-Thihli, Khalid Al Futaisi, Amna Al Mamari, Watfa Al-Murshedi, Fathiya Al-Jasmi, Fatma |
author_sort | Al Busaidi, Marwa |
collection | PubMed |
description | BACKGROUND: In metabolic stress, the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) enzyme is involved in energy production through the gluconeogenesis pathway. PEPCK-C deficiency is a rare childhood-onset autosomal recessive metabolic disease caused by PCK1 genetic defects. Previous studies showed a broad clinical spectrum ranging from asymptomatic to recurrent hypoglycemia with/without lactic acidosis, encephalopathy, seizures, and liver failure. RESULTS: In this article, we discuss the occurrence of PEPCK-C deficiency in four families from the United Arab Emirates and Oman. All patients presented with unexplained hypoglycemia as a common feature. Two out of the seven patients presented with episodes of encephalopathy that resulted in seizures and neuroregression leading to global developmental delay and one patient had a neonatal presentation. Observed biochemical abnormalities include elevated lactate, transaminases, and tricarboxylic acid cycle metabolites in most patients. Elevated creatine kinase was documented in two patients. Whole exome sequencing revealed two novel (c.574T > C, and c.1268 C > T) and a previously reported splice site (c.961 + 1G > A) PCK1 variant in the affected families. CONCLUSION: Patients become vulnerable during intercurrent illness; thus, prevention and prompt reversal of a catabolic state are crucial to avoid irreversible brain damage. This report will help to expand the clinical understanding of this rare disease and recommends screening for PEPCK-C deficiency in unexplained hypoglycemia. |
format | Online Article Text |
id | pubmed-10625263 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106252632023-11-05 Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families Al Busaidi, Marwa Mohamed, Feda E. Al-Ajmi, Eiman Al Hashmi, Nadia Al-Thihli, Khalid Al Futaisi, Amna Al Mamari, Watfa Al-Murshedi, Fathiya Al-Jasmi, Fatma Orphanet J Rare Dis Research BACKGROUND: In metabolic stress, the cytosolic phosphoenolpyruvate carboxykinase (PEPCK-C) enzyme is involved in energy production through the gluconeogenesis pathway. PEPCK-C deficiency is a rare childhood-onset autosomal recessive metabolic disease caused by PCK1 genetic defects. Previous studies showed a broad clinical spectrum ranging from asymptomatic to recurrent hypoglycemia with/without lactic acidosis, encephalopathy, seizures, and liver failure. RESULTS: In this article, we discuss the occurrence of PEPCK-C deficiency in four families from the United Arab Emirates and Oman. All patients presented with unexplained hypoglycemia as a common feature. Two out of the seven patients presented with episodes of encephalopathy that resulted in seizures and neuroregression leading to global developmental delay and one patient had a neonatal presentation. Observed biochemical abnormalities include elevated lactate, transaminases, and tricarboxylic acid cycle metabolites in most patients. Elevated creatine kinase was documented in two patients. Whole exome sequencing revealed two novel (c.574T > C, and c.1268 C > T) and a previously reported splice site (c.961 + 1G > A) PCK1 variant in the affected families. CONCLUSION: Patients become vulnerable during intercurrent illness; thus, prevention and prompt reversal of a catabolic state are crucial to avoid irreversible brain damage. This report will help to expand the clinical understanding of this rare disease and recommends screening for PEPCK-C deficiency in unexplained hypoglycemia. BioMed Central 2023-11-03 /pmc/articles/PMC10625263/ /pubmed/37924129 http://dx.doi.org/10.1186/s13023-023-02946-5 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Al Busaidi, Marwa Mohamed, Feda E. Al-Ajmi, Eiman Al Hashmi, Nadia Al-Thihli, Khalid Al Futaisi, Amna Al Mamari, Watfa Al-Murshedi, Fathiya Al-Jasmi, Fatma Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title | Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title_full | Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title_fullStr | Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title_full_unstemmed | Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title_short | Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families |
title_sort | expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel pck1 variants in four arabian gulf families |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625263/ https://www.ncbi.nlm.nih.gov/pubmed/37924129 http://dx.doi.org/10.1186/s13023-023-02946-5 |
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