Phosphoenolpyruvate carboxykinase deficiency
Synonyms: PEPCK deficiency
- Type
- Disease
- Group
- Disorder
- Inheritance
- Autosomal recessive, Mitochondrial inheritance
- Age of onset
- Infancy, Neonatal
- Status
- active
A rare gluconeogenesis disorder characterized by recurrent hypoglycemia mostly associated with acute episodes of severe lactic acidosis and hepatic dysfunction including liver failure due to phosphoenolpyruvate carboxykinase enzyme deficiency. Hypoglycemic seizures occur predominantly at the age of 1-2 years and mostly in the mornings. However they can also present neonatally or at a later age, and could re-occur during school age or adulthood. Patients have recognizable pattern of abnormal urine organicacids (including increased tricarboxylic acid cycle metabolites) and inadequate ketone body production during hypoglycemia. Some patients may also have encephalopathy, cerebral edema and seizures thay may result in neuroregression and/or global developmental delay associated to failure to manage hypoglycemia. Some patients may also be asymptomatic.
Names in Orphadata languages
12 of 12 languages| Lang | Name | Synonyms |
|---|---|---|
| en | Phosphoenolpyruvate carboxykinase deficiency | PEPCK deficiency |
| fr | Déficit en phosphoénolpyruvate carboxykinase | Déficit en PEPCK |
| de | Phosphoenolpyruvat-Carboxykinase-Mangel | PEPCK-Mangel |
| es | Deficiencia de fosfoenolpiruvato carboxiquinasa | Deficiencia de PEPCK |
| it | Deficit di fosfoenolpiruvato carbossichinasi | Deficit di PEPCK |
| nl | Deficiëntie van fosfo-enolpyruvaat-carboxykinase | PEPCK-deficiëntie |
| pt | Deficiência de fosfoenolpiruvato carboxicinase | Deficiência de PEPCK |
| pl | Niedobór karboksykinazy fosfolenolopirogronianowej | Niedobór PEPCK |
| cs | Deficit fosfoenolpyruvát karboxykinázy | PEPCK deficit |
| uk | Дефіцит фосфоенолпіруваткарбоксикінази | Дефіцит PEPCK |
| zh | 磷酸烯醇式丙酮酸羧激酶缺乏症 | PEPCK缺乏症 |
| tr | Fosfoenolpiruvat karboksikinaz eksikliği | PEPCK eksikliği |
Definition in:
Cross-references
qualifier = Orphanet mapping relation| Source | Code | Qualifier | ICD relation | Validation |
|---|---|---|---|---|
| OMIM | 261650 | BTNT | validated | |
| OMIM | 261680 | BTNT | validated | |
| ICD-10 | E74.4 | NTBT | inclusion | validated |
| ICD-11 | 5C53.0Y | NTBT | index | validated |
| MONDO | 0017320 | E | validated | |
| MeSH | C536654 | E | validated | |
| UMLS | C0268194 | E | validated |
E exact · NTBT this ORPHAcode is narrower than the target · BTNT broader than the target · ND not decided.
Classification
Preferential parent (Orphanet linearisation):
Parents in the classifications (1):
- ORPHA:79177Gluconeogenesis disorder
rare inborn errors of metabolism; rare genetic diseases
No children.
Codes that Orphanet moved or referred to this one:
- ORPHA:79316OBSOLETE: Phosphoenolpyruvate carboxykinase 1 deficiency referred to · inactive
- ORPHA:79317OBSOLETE: Phosphoenolpyruvate carboxykinase 2 deficiency referred to · inactive
Genes
2 direct| Gene | Association | Status | HGNC | Ensembl | OMIM | Locus | Name | Source of validation |
|---|---|---|---|---|---|---|---|---|
| PCK1 | Disease-causing germline mutation(s) in | Assessed | HGNC:8724 | ENSG00000124253 | 614168 | 20q13.31 | phosphoenolpyruvate carboxykinase 1 | |
| PCK2 | Disease-causing germline mutation(s) in | Assessed | HGNC:8725 | ENSG00000100889 | 614095 | 14q11.2-q12 | phosphoenolpyruvate carboxykinase 2, mitochondrial | 2044592[PMID] |
Prevalence and incidence
2 records| Type | Class | Value | Area | Qualification | Validation | Source |
|---|---|---|---|---|---|---|
| Cases/families | 10 cases | Worldwide | Case(s) | Validated | ORPHANET | |
| Point prevalence | <1 / 1 000 000 | — | Worldwide | Class only | Validated | ORPHANET |
Value is Orphadata's ValMoy: the mean estimate per 100 000 for prevalence and incidence, the number of cases or families for case reports.
HPO phenotypes
22 annotations · validated 2025-06-04| HPO | Term (as annotated by Orphanet) | Diagnostic |
|---|---|---|
| Very frequent (99-80%) | ||
| HP:0001988 | Recurrent hypoglycemia | |
| Frequent (79-30%) | ||
| HP:0031964 | Elevated circulating alanine aminotransferase concentration | |
| HP:0031956 | Elevated circulating aspartate aminotransferase concentration | |
| HP:0034648 | Elevated urine fumaric acid level | |
| HP:0003217 | Hyperglutaminemia | |
| HP:0002173 | Hypoglycemic seizures | |
| HP:0002151 | Increased circulating lactate concentration | |
| HP:0012402 | Increased urine alpha-ketoglutarate concentration | |
| HP:0003128 | Lactic acidosis | |
| HP:0003648 | Lacticaciduria | |
| Occasional (29-5%) | ||
| HP:0006846 | Acute encephalopathy | |
| HP:0001410 | Decreased liver function | |
| HP:0002329 | Drowsiness | |
| HP:0001397 | Hepatic steatosis | |
| HP:0001325 | Hypoglycemic coma | |
| HP:0001252 | Hypotonia | |
| HP:0001254 | Lethargy | |
| HP:0001998 | Neonatal hypoglycemia | |
| HP:0012758 | Neurodevelopmental delay | |
| HP:0002013 | Vomiting | |
| Very rare (<4-1%) | ||
| HP:0001987 | Hyperammonemia | |
| HP:0000252 | Microcephaly | |
Run the differential on the 1 obligate / very frequent terms
Annotation source: 33445193[PMID]_34622459[PMID]_35868242[PMID]_37924129[PMID]
Sources for this card
- Orphanet page: orpha.net/en/disease/detail/2880
- This record as JSON: /data/d/2880.json