Expanding the clinical spectrum of cytosolic phosphoenolpyruvate carboxykinase deficiency: novel PCK1 variants in four Arabian Gulf families: novel PCK1 variants in four Arabian Gulf families

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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number344
Pages (from-to)344
JournalOrphanet Journal of Rare Diseases
Volume18
Issue number1
DOIs
Publication statusPublished - Nov 3 2023

Keywords

  • Brain Diseases
  • Child
  • Humans
  • Hypoglycemia/etiology
  • Infant, Newborn
  • Intracellular Signaling Peptides and Proteins
  • Liver Diseases/complications
  • Phosphoenolpyruvate Carboxykinase (GTP)/genetics
  • Seizures/genetics

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