Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-023-02946-5 |
| _version_ | 1797636678357090304 |
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| author | Marwa Al Busaidi Feda E. Mohamed Eiman Al-Ajmi Nadia Al Hashmi Khalid Al-Thihli Amna Al Futaisi Watfa Al Mamari Fathiya Al-Murshedi Fatma Al-Jasmi |
| author_facet | Marwa Al Busaidi Feda E. Mohamed Eiman Al-Ajmi Nadia Al Hashmi Khalid Al-Thihli Amna Al Futaisi Watfa Al Mamari Fathiya Al-Murshedi Fatma Al-Jasmi |
| author_sort | Marwa Al Busaidi |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-11T12:37:33Z |
| format | Article |
| id | doaj.art-4c46b9ee8ba94f4794bc083e28077f10 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-11T12:37:33Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-4c46b9ee8ba94f4794bc083e28077f102023-11-05T12:29:23ZengBMCOrphanet Journal of Rare Diseases1750-11722023-11-0118111010.1186/s13023-023-02946-5Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf familiesMarwa Al Busaidi0Feda E. Mohamed1Eiman Al-Ajmi2Nadia Al Hashmi3Khalid Al-Thihli4Amna Al Futaisi5Watfa Al Mamari6Fathiya Al-Murshedi7Fatma Al-Jasmi8College of Medicine and Health Sciences, Sultan Qaboos UniversityGenetics and Genomics Department, College of Medicine and Health Sciences, United Arab Emirates UniversityDepartment of Radiology and Molecular Imaging, Sultan Qaboos University HospitalDepartment of Pediatrics, The Royal HospitalDepartment of Genetic and Developmental Medicine Clinic, Sultan Qaboos University HospitalDepartment of Child Health, College of Medicine and Health Sciences, Sultan Qaboos UniversityDepartment of Child Health, College of Medicine and Health Sciences, Sultan Qaboos UniversityDepartment of Genetic and Developmental Medicine Clinic, Sultan Qaboos University HospitalGenetics and Genomics Department, College of Medicine and Health Sciences, United Arab Emirates UniversityAbstract 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.https://doi.org/10.1186/s13023-023-02946-5Phosphoenolpyruvate CarboxykinaseHypoglycemiaEncephalopathyPCK1 |
| spellingShingle | Marwa Al Busaidi Feda E. Mohamed Eiman Al-Ajmi Nadia Al Hashmi Khalid Al-Thihli Amna Al Futaisi Watfa Al Mamari Fathiya Al-Murshedi Fatma Al-Jasmi Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families Orphanet Journal of Rare Diseases Phosphoenolpyruvate Carboxykinase Hypoglycemia Encephalopathy PCK1 |
| 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 | Phosphoenolpyruvate Carboxykinase Hypoglycemia Encephalopathy PCK1 |
| url | https://doi.org/10.1186/s13023-023-02946-5 |
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