{"orpha":2880,"name":"Phosphoenolpyruvate carboxykinase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["PEPCK deficiency"],"definition":"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.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-2880/","orphanet_url":"https://www.orpha.net/en/disease/detail/2880","names":{"fr":{"name":"Déficit en phosphoénolpyruvate carboxykinase","synonyms":["Déficit en PEPCK"],"definition":"Trouble rare de la gluconéogenèse caractérisé par une hypoglycémie récurrente associée principalement à des épisodes aigus d'acidose lactique sévère et de dysfonctionnement hépatique, y compris une insuffisance hépatique due à un déficit en enzyme phosphoénolpyruvate carboxykinase. Les crises hypoglycémiques surviennent principalement entre 1 et 2&nbsp;ans, surtout le matin. Elles peuvent toutefois apparaître également à la naissance ou à un âge plus avancé, et se reproduire à l'âge scolaire ou à l'âge adulte. Le profil de ces patients est reconnaissable par la présence d'acides organiques anormaux dans l'urine (y compris une augmentation des métabolites du cycle de l'acide tricarboxylique) et une production insuffisante de corps cétoniques pendant l'hypoglycémie. Certains patients peuvent également présenter une encéphalopathie, un oedème cérébral et des crises pouvant entraîner une régression neurologique et/ou un retard global du développement associé à une incapacité à gérer l'hypoglycémie. Certains patients peuvent également être asymptomatiques."},"de":{"name":"Phosphoenolpyruvat-Carboxykinase-Mangel","synonyms":["PEPCK-Mangel"],"definition":"Eine seltene Störung der Glukoneogenese, die durch wiederkehrende Hypoglykämie gekennzeichnet ist, die meist mit akuten Episoden schwerer Laktatazidose und Leberfunktionsstörungen, einschließlich Leberversagen aufgrund eines Phosphoenolpyruvat-Carboxykinase-Enzymmangels, einhergeht. Hypoglykämische Anfälle treten vorwiegend im Alter von 1 bis 2 Jahren und meist morgens auf. Sie können jedoch auch bei Neugeborenen oder in einem späteren Alter auftreten und im Schulalter oder im Erwachsenenalter wiederkehren. Die Patienten weisen ein erkennbares Muster abnormaler organischer Säuren im Urin (einschließlich erhöhter Metaboliten des Tricarbonsäurezyklus) und eine unzureichende Ketonkörperproduktion während der Hypoglykämie auf. Einige Patienten können auch an Enzephalopathie, Hirnödem und Krampfanfällen leiden, die zu einer Neuroregression und/oder einer globalen Entwicklungsverzögerung führen können, die mit der Unfähigkeit zur Bewältigung der Hypoglykämie verbunden ist. Einige Patienten können auch asymptomatisch sein."},"es":{"name":"Deficiencia de fosfoenolpiruvato carboxiquinasa","synonyms":["Deficiencia de PEPCK"],"definition":"Es un trastorno poco frecuente de la gluconeogénesis caracterizado por hipoglucemia recurrente, asociada principalmente a episodios agudos de acidosis láctica grave y disfunción hepática, incluyendo insuficiencia hepática por deficiencia de la enzima fosfoenolpiruvato carboxiquinasa. Las crisis hipoglucémicas se presentan predominantemente entre los 1 y los 2 años de edad, principalmente por las mañanas. Sin embargo, también pueden manifestarse en el periodo neonatal o a una edad posterior, y podrían reaparecer durante la edad escolar o la edad adulta. Los pacientes presentan un patrón anómalo reconocible de ácidos orgánicos urinarios (incluyendo un aumento de los metabolitos del ciclo del ácido tricarboxílico) y una producción inadecuada de cuerpos cetónicos durante la hipoglucemia. Algunos pacientes también pueden presentar encefalopatía, edema cerebral y crisis epilépticas que pueden provocar neurorregresión o retraso global del desarrollo asociado al fracaso en el control de la hipoglucemia. Algunos pacientes pueden permanecer asintomáticos."},"it":{"name":"Deficit di fosfoenolpiruvato carbossichinasi","synonyms":["Deficit di PEPCK"],"definition":"Il deficit di fosfoenolpiruvato carbossichinasi (PEPCK) è una malattia della gluconeogenesi, causata da un difetto dell'enzima PEPCK; comprende le forme citosolica (PEPCK1) e mitocondriale (PEPCK2) del deficit enzimatico. I sintomi esordiscono in epoca neonatale, di solito nei primi mesi di vita, e comprendono l'ipoglicemia associata ad episodi acuti di acidosi lattica grave, il deterioramento neurologico progressivo, l'insufficienza epatica grave, l'acidosi tubulare renale e la sindrome di Fanconi. Inoltre, i pazienti presentano danni multisistemici progressivi, ritardo della crescita, debolezza e ipotonia muscolare, ritardo dello sviluppo associato a crisi epilettiche, spasticità, letargia, microcefalia e cardiomiopatia. Non esiste al momento alcuna evidenza che via sia una forma isolata della malattia."},"nl":{"name":"Deficiëntie van fosfo-enolpyruvaat-carboxykinase","synonyms":["PEPCK-deficiëntie"],"definition":"Een zeldzame aandoening van de gluconeogenese, gekenmerkt door recidiverende hypoglycemie, meestal geassocieerd met acute episodes van ernstige lactaatacidose en leverdisfunctie met inbegrip van leverfalen door deficiëntie van het enzym fosfo-enolpyruvaatcarboxykinase. Hypoglycemische aanvallen komen voornamelijk voor op een van 1-2 jaar en meestal in de ochtend. Ze kunnen echter ook neonataal of op latere leeftijd optreden, en kunnen opnieuw optreden op schoolgaande leeftijd of in de volwassenheid. Patiënten hebben een herkenbaar afwijkend patroon van organische zuren in de urine (waaronder verhoogde gehaltes van metabolieten van de tricarbonzuurcyclus) en ontoereikende productie van ketonlichamen tijdens hypoglycemie. Sommige patiënten hebben mogelijk ook encefalopathie, cerebraal oedeem en insulten die kunnen resulteren in neurologische regressie en/of algehele ontwikkelingsachterstand geassocieerd met gefaalde regulatie van hypoglycemie. Sommige patiënten kunnen asymptomatisch zijn."},"pt":{"name":"Deficiência de fosfoenolpiruvato carboxicinase","synonyms":["Deficiência de PEPCK"]},"pl":{"name":"Niedobór karboksykinazy fosfolenolopirogronianowej","synonyms":["Niedobór PEPCK"],"definition":"Rzadkie zaburzenie glukoneogenezy, które wynika z upośledzenia aktywności enzymu karboksykinazy fosfoenolopirogronianowej i obejmuje cytozolowe i mitochondrialne postaci niedoboru enzymu. Początek objawów przypada na okres noworodkowy lub kilka miesięcy po urodzeniu i obejmują one hipoglikemię związaną z ostrymi epizodami ciężkiej kwasicy mleczanowej, postępujące pogorszenie stanu neurologicznego, ciężką niewydolność wątroby, nerkową kwasicę kanalikową oraz zespół Fanconiego. U pacjentów obserwuje się uszkodzenie wielonarządowe z opóźnieniem wzrastania, osłabienie mięśni i obniżenie napięcia mięśniowego, opóźnienie rozwoju z drgawkami, spastycznością, sennością, małogłowiem i kardiomiopatią. Do tej pory nie ma jednoznacznych dowodów na istnienie izolowanej postaci tego zaburzenia."},"cs":{"name":"Deficit fosfoenolpyruvát karboxykinázy","synonyms":["PEPCK deficit"]},"uk":{"name":"Дефіцит фосфоенолпіруваткарбоксикінази","synonyms":["Дефіцит PEPCK"],"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."},"zh":{"name":"磷酸烯醇式丙酮酸羧激酶缺乏症","synonyms":["PEPCK缺乏症"]},"tr":{"name":"Fosfoenolpiruvat karboksikinaz eksikliği","synonyms":["PEPCK eksikliği"]}},"xrefs":[{"source":"OMIM","code":"261650","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"261680","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E74.4","qualifier":"NTBT","icd_relation":"inclusion","validated":true},{"source":"ICD-11","code":"5C53.0Y","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1350463176"},{"source":"MONDO","code":"0017320","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C536654","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C0268194","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[{"type":"Referred to","orpha":79316,"name":"OBSOLETE: Phosphoenolpyruvate carboxykinase 1 deficiency","status":"inactive"},{"type":"Referred to","orpha":79317,"name":"OBSOLETE: Phosphoenolpyruvate carboxykinase 2 deficiency","status":"inactive"}],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":79177,"name":"Gluconeogenesis disorder","classifications":[150,156]}],"children":[],"genes":[{"symbol":"PCK1","name":"phosphoenolpyruvate carboxykinase 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"8724","ensembl":"ENSG00000124253","omim":"614168","loci":["20q13.31"]},{"symbol":"PCK2","name":"phosphoenolpyruvate carboxykinase 2, mitochondrial","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"2044592[PMID]","hgnc":"8725","ensembl":"ENSG00000100889","omim":"614095","loci":["14q11.2-q12"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive","Mitochondrial inheritance"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":10.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2025-06-04","source":"33445193[PMID]_34622459[PMID]_35868242[PMID]_37924129[PMID]","terms":[{"hpo":"HP:0001988","label":"Recurrent hypoglycemia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0031964","label":"Elevated circulating alanine aminotransferase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0031956","label":"Elevated circulating aspartate aminotransferase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034648","label":"Elevated urine fumaric acid level","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003217","label":"Hyperglutaminemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002173","label":"Hypoglycemic seizures","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012402","label":"Increased urine alpha-ketoglutarate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003648","label":"Lacticaciduria","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006846","label":"Acute encephalopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001410","label":"Decreased liver function","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002329","label":"Drowsiness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001397","label":"Hepatic steatosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001325","label":"Hypoglycemic coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001998","label":"Neonatal hypoglycemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012758","label":"Neurodevelopmental delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001987","label":"Hyperammonemia","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Very rare (<4-1%)","criteria":null}]}}