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Phosphoenolpyruvate carboxykinase deficiency, cytosolic(PCKDC)

MedGen UID:
1801754
Concept ID:
C5574905
Disease or Syndrome
Synonyms: PCK1 DEFICIENCY, CYTOSOLIC; PCKDC; PEPCK DEFICIENCY, CYTOSOLIC
 
Gene (location): PCK1 (20q13.31)
 
Monarch Initiative: MONDO:0009866
OMIM®: 261680

Definition

Cytosolic phosphoenolpyruvate carboxykinase deficiency causes a defect in gluconeogenesis that results in a 'biochemical signature' of fasting hypoglycemia with high tricarboxylic acid cycle intermediate excretion, particularly of fumarate. Other biochemical anomalies that may be seen during metabolic crisis include ketonuria, dicarboxylic aciduria, and urea cycle dysfunction (Vieira et al., 2017). See PCKDM (261650) for a discussion of mitochondrial PCK (PEPCK2; 614095) deficiency. [from OMIM]

Clinical features

From HPO
Ketonuria
MedGen UID:
56402
Concept ID:
C0162275
Finding
High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state.
Renal steatosis
MedGen UID:
867423
Concept ID:
C4021796
Disease or Syndrome
Abnormal fat accumulation in the kidneys.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Liver failure
MedGen UID:
88444
Concept ID:
C0085605
Disease or Syndrome
A disorder characterized by the inability of the liver to metabolize chemicals in the body. Causes include cirrhosis and drug-induced hepatotoxicity. Signs and symptoms include jaundice and encephalopathy. Laboratory test results reveal abnormal plasma levels of ammonia, bilirubin, lactic dehydrogenase, and alkaline phosphatase.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Increased hepatic echogenicity
MedGen UID:
1382460
Concept ID:
C4477000
Finding
Increased echogenicity of liver tissue on sonography, manifested as an increased amount of white on the screen of the sonography device.
Hepatic encephalopathy
MedGen UID:
5513
Concept ID:
C0019151
Disease or Syndrome
Central nervous system dysfunction in association with liver failure and characterized clinically (depending on degree of severity) by lethargy, confusion, nystagmus, decorticate posturing, spasticity, and bilateral Babinski reflexes.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
EEG abnormality
MedGen UID:
56235
Concept ID:
C0151611
Finding
Abnormality observed by electroencephalogram (EEG), which is used to record of the brain's spontaneous electrical activity from multiple electrodes placed on the scalp.
Cerebral atrophy
MedGen UID:
116012
Concept ID:
C0235946
Disease or Syndrome
Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Apnea
MedGen UID:
2009
Concept ID:
C0003578
Sign or Symptom
Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event.
Lactic acidosis
MedGen UID:
1717
Concept ID:
C0001125
Disease or Syndrome
An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.
Hypoglycemia
MedGen UID:
6979
Concept ID:
C0020615
Disease or Syndrome
A decreased concentration of glucose in the blood.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
Fasting hypoglycemia
MedGen UID:
75765
Concept ID:
C0271708
Disease or Syndrome
HYPOGLYCEMIA expressed in the postabsorptive state, after prolonged FASTING, or an overnight fast.
Low plasma citrulline
MedGen UID:
326522
Concept ID:
C1839532
Finding
A decreased concentration of citrulline in the blood.
Impaired gluconeogenesis
MedGen UID:
480966
Concept ID:
C3279336
Finding
An impairment of gluconeogenesis.
Reduced phosphoenolpyruvate carboxykinase activity in cultured fibroblasts
MedGen UID:
1053802
Concept ID:
CN377451
Finding
Activity of phosphoenolpyruvate carboxykinase (EC 4.1.1.32) is below the lower limit of normal in cultured fibroblasts.
Cyanosis
MedGen UID:
1189
Concept ID:
C0010520
Sign or Symptom
Bluish discoloration of the skin and mucosa due to poor circulation or inadequate oxygenation of arterial or capillary blood.
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.

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

Diagnosis

Goetz M, Schröter J, Dattner T, Brennenstuhl H, Lenz D, Opladen T, Hörster F, Okun JG, Hoffmann GF, Kölker S, Staufner C
Mol Genet Metab 2022 Sep-Oct;137(1-2):18-25. Epub 2022 Jul 11 doi: 10.1016/j.ymgme.2022.07.007. PMID: 35868242
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
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

Goetz M, Schröter J, Dattner T, Brennenstuhl H, Lenz D, Opladen T, Hörster F, Okun JG, Hoffmann GF, Kölker S, Staufner C
Mol Genet Metab 2022 Sep-Oct;137(1-2):18-25. Epub 2022 Jul 11 doi: 10.1016/j.ymgme.2022.07.007. PMID: 35868242
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

Clinical prediction guides

Al Busaidi M, Mohamed FE, Al-Ajmi E, Al Hashmi N, Al-Thihli K, Al Futaisi A, Al Mamari W, Al-Murshedi F, Al-Jasmi F
Orphanet J Rare Dis 2023 Nov 3;18(1):344. doi: 10.1186/s13023-023-02946-5. PMID: 37924129Free PMC Article
Goetz M, Schröter J, Dattner T, Brennenstuhl H, Lenz D, Opladen T, Hörster F, Okun JG, Hoffmann GF, Kölker S, Staufner C
Mol Genet Metab 2022 Sep-Oct;137(1-2):18-25. Epub 2022 Jul 11 doi: 10.1016/j.ymgme.2022.07.007. PMID: 35868242

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