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Phosphoenolpyruvate carboxykinase (GTP) deficiency

MedGen UID:
120618
Concept ID:
C0268194
Disease or Syndrome
Synonyms: PEP carboxykinase deficiency; PEPCK 1 deficiency; Phosphoenolpyruvate Carboxykinase Deficiency; Phosphoenolpyruvate carboxykinase-1 (PCK1) deficiency; Phosphoenolpyruvate carboxylase deficiency; Phosphopyruvate carboxylase deficiency
SNOMED CT: Phosphoenolpyruvate carboxykinase deficiency (5335002); PEPCK - Phosphoenolpyruvate carboxykinase deficiency (5335002); Phosphoenolpyruvate carboxykinase (GTP) deficiency (5335002)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Mitochondrial inheritance
MedGen UID:
165802
Concept ID:
C0887941
Genetic Function
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on the mitochondrial genome. Because the mitochondrial genome is essentially always maternally inherited, a mitochondrial condition can only be transmitted by females, although the condition can affect both sexes. The proportion of mutant mitochondria can vary (heteroplasmy).
 
Monarch Initiative: MONDO:0017320
Orphanet: ORPHA2880

Definition

A rare gluconeogenesis disorder that results from impairment in the enzyme phosphoenolpyruvate carboxykinase, and comprised of cytosolic and mitochondrial forms of enzyme deficiency. Onset of symptoms is neonatal or a few months after birth and includes hypoglycemia associated with acute episodes of severe lactic acidosis, progressive neurological deterioration, severe liver failure, renal tubular acidosis and Fanconi syndrome. Patients also present progressive multisystem damage with failure to thrive, muscular weakness and hypotonia, developmental delay with seizures, spasticity, lethargy, microcephaly and cardiomyopathy. To date, there is no conclusive evidence of the existence of an isolated form of this disorder. [from ORDO]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVPhosphoenolpyruvate carboxykinase (GTP) deficiency
Follow this link to review classifications for Phosphoenolpyruvate carboxykinase (GTP) deficiency in Orphanet.

Recent clinical studies

Etiology

Vieira P, Nagy II, Rahikkala E, Väisänen ML, Latva K, Kaunisto K, Valmari P, Keski-Filppula R, Haanpää MK, Sidoroff V, Miettinen PJ, Arkkola T, Ojaniemi M, Nuutinen M, Uusimaa J, Myllynen P
J Inherit Metab Dis 2022 Mar;45(2):223-234. Epub 2021 Nov 11 doi: 10.1002/jimd.12446. PMID: 34622459
Leonard JV
Ciba Found Symp 1982;87:340-56. doi: 10.1002/9780470720691.ch19. PMID: 6280937
Naeye RL
Arch Pathol Lab Med 1977 Apr;101(4):165-7. PMID: 322636

Diagnosis

Vieira P, Nagy II, Rahikkala E, Väisänen ML, Latva K, Kaunisto K, Valmari P, Keski-Filppula R, Haanpää MK, Sidoroff V, Miettinen PJ, Arkkola T, Ojaniemi M, Nuutinen M, Uusimaa J, Myllynen P
J Inherit Metab Dis 2022 Mar;45(2):223-234. Epub 2021 Nov 11 doi: 10.1002/jimd.12446. PMID: 34622459
Becker J, Haas NA, Vlaho S, Heineking B, Wortmann SB, Rabenhorst D, Thomas C, Brunet T
Neuropediatrics 2021 Oct;52(5):398-402. Epub 2021 Jan 14 doi: 10.1055/s-0040-1722685. PMID: 33445193
Vieira P, Cameron J, Rahikkala E, Keski-Filppula R, Zhang LH, Santra S, Matthews A, Myllynen P, Nuutinen M, Moilanen JS, Rodenburg RJ, Rolfs A, Uusimaa J, van Karnebeek CDM
Mol Genet Metab 2017 Apr;120(4):337-341. Epub 2017 Feb 6 doi: 10.1016/j.ymgme.2017.02.003. PMID: 28216384
van den Berghe G
J Inherit Metab Dis 1996;19(4):470-7. doi: 10.1007/BF01799108. PMID: 8884571
Leonard JV, Hyland K, Furukawa N, Clayton PT
Eur J Pediatr 1991 Jan;150(3):198-9. doi: 10.1007/BF01963566. PMID: 2044592

Therapy

Santra S, Cameron JM, Shyr C, Zhang L, Drögemöller B, Ross CJ, Wasserman WW, Wevers RA, Rodenburg RJ, Gupte G, Preece MA, van Karnebeek CD
Mol Genet Metab 2016 May;118(1):21-7. Epub 2016 Mar 4 doi: 10.1016/j.ymgme.2016.03.001. PMID: 26971250

Prognosis

Becker J, Haas NA, Vlaho S, Heineking B, Wortmann SB, Rabenhorst D, Thomas C, Brunet T
Neuropediatrics 2021 Oct;52(5):398-402. Epub 2021 Jan 14 doi: 10.1055/s-0040-1722685. PMID: 33445193
Oishi K, Siegel C, Cork EE, Chen H, Imagawa E
J Hum Genet 2021 Mar;66(3):321-325. Epub 2020 Sep 9 doi: 10.1038/s10038-020-00823-8. PMID: 32908218
van den Berghe G
J Inherit Metab Dis 1996;19(4):470-7. doi: 10.1007/BF01799108. PMID: 8884571

Clinical prediction guides

Duś-Żuchowska M, Nowak H, Kałużny Ł, Rokicki D, Ciara E, Piekutowska-Abramczuk D, Walkowiak J
Am J Case Rep 2024 Apr 24;25:e943118. doi: 10.12659/AJCR.943118. PMID: 38656928Free PMC Article
McGraw CA, Vawter GF, Hug G
Forensic Sci Int 1986 Feb-Mar;30(2-3):143-54. doi: 10.1016/0379-0738(86)90009-5. PMID: 3957187

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