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Disease Profile

PEPCK 1 deficiency

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Phosphoenolpyruvate carboxykinase-1 (PCK1) deficiency; Phosphopyruvate carboxylase deficiency; Phosphoenolpyruvate carboxylase deficiency;

Summary

PEPCK1 deficiency is a rare inborn error of metabolism disorder, characterized by the deficiency of the enzyme PEPCK1, one of the enzymes needed for gluconeogenesis, the process by which organisms produce sugars (namely glucose) from non-carbohydrate precursors (such as amino acids).[1][2] The symptoms described in the few cases reported in the medical literature suggest that there may be variation in the severity of the symptoms ranging from severe early-onset cases, to milder late-onset presentations. In severe cases symptoms may include persistent and very low levels of blood's sugar in newborns (neonatal hypoglycemia), failure to thrive, build-up of lactic acid in the blood (lactic acidosis), liver enlargement (hepatomegaly) and liver failure leading to neurological degeneration. Milder cases present during childhood with fewer and less serious liver problems. Infections and fasting may trigger the symptoms.[2][3] PEPCK1 deficiency inheritance is autosomal recessive. It is caused by mutations in the PEPCK1 gene.[4] Some researchers believe that the severity of the disease depend upon the mutations resulting in less or more PEPCK1 activity (the more active the enzyme is, the less severe the disease is, and vice versa). Treatment depend on the symptoms and may include giving extra carbohydrates during heavy exercise and illness or other times of fasting (formal sick day regimen) by the dietitian.[3]

PEPCK1 is the cytosolic form of the phosphoenolpyruvate carboxykinase (PEPCK) enzyme, the other being the mitochondrial (PEPCK2).[5] 

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
Percent of people who have these symptoms is not available through HPO
Apnea
0002104
Autosomal recessive inheritance
0000007
Cerebral atrophy
Degeneration of cerebrum
0002059
Cyanosis
Blue discoloration of the skin
0000961
EEG abnormality
0002353
Fasting hypoglycemia
Low blood sugar when fasting
0003162
Global developmental delay
0001263
Hepatic encephalopathy
0002480
Hepatic failure
Liver failure
0001399
Hepatic steatosis
Fatty infiltration of liver
Fatty liver

[ more ]

0001397
Hepatomegaly
Enlarged liver
0002240
Impaired gluconeogenesis
0005959
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Ketonuria
0002919
Lactic acidosis
Increased lactate in body
0003128
Low plasma citrulline
0003572
Optic atrophy
0000648
Renal steatosis
Fatty kidney
0000799
Seizure
0001250

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • PubMed is a searchable database of medical literature and lists journal articles that discuss PEPCK 1 deficiency. Click on the link to view a sample search on this topic.

References

  1. PCK1 gene. Genetics Home Reference. https://www.ncbi.nlm.nih.gov/pubmed/28216384.
  2. Vidnes J & Sovik O. Gluconeogenesis in infancy and childhood. III. Deficiency of the extramitochondrial form of hepatic phosphoenolpyruvate carboxykinase in a case of persistent neonatal hypoglycaemia. Acta Paediatr Scand. May, 1976; 65(3):307-12. https://www.ncbi.nlm.nih.gov/pubmed/1274563.
  3. Vieira P, Cameron J, Rahikkala E, et al. Novel homozygous PCK1 mutation causing cytosolic phosphoenolpyruvate carboxykinase deficiency presenting as childhood hypoglycemia, an abnormal pattern of urine metabolites and liver dysfunction. Mol Genet Metab. April, 2017; 120(4):337-341. https://www.ncbi.nlm.nih.gov/pubmed/28216384.
  4. Phosphoenolpyruvate carboxykinase-1, cytosolic, deficiency. OMIMM. 2016; https://www.omim.org/entry/261680.
  5. Phosphoenolpyruvate carboxykinase deficiency. Orphanet. 2016; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=2880.