{"orpha":555402,"name":"NAD(P)HX dehydratase deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["CARKD deficiency"],"definition":"A rare neurometabolic disease characterized by infantile onset of repeated episodes of developmental regression and neurodegeneration, often triggered by febrile illnesses. Patients present with lethargy, hypotonia, irritability, gait ataxia, loss of speech, movement disorder, seizures, ophthalmoplegia, and hearing loss. Brain imaging shows generalized cerebral atrophy and bilateral basal ganglia abnormalities. Extensive skin lesions, cardiomyopathy, and pancytopenia have been reported in association. The condition is fatal in the first years of life.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-555402/","orphanet_url":"https://www.orpha.net/en/disease/detail/555402","names":{"fr":{"name":"Déficit en NAD(P)HX déshydratase","synonyms":["Déficit en CARKD"],"definition":"Maladie neurométabolique rare caractérisée par des épisodes répétés de régression du développement global pendant la période infantile et de neurodégénérescence, souvent déclenchés par des maladies fébriles. Les patients manifestent une léthargie, une hypotonie, une irritabilité, une ataxie de la marche, une perte de l'élocution, des troubles du mouvement, des crises convulsives, une ophtalmoplégie et une perte d'audition. L'IRM révèle une atrophie cérébrale généralisée et des malformations bilatérales des ganglions de la base. On rapporte l'association avec des lésions cutanées étendues, une cardiomyopathie et une pancytopénie. La maladie est létale dans les premières années de la vie."},"de":{"name":"NAD(P)HX-Dehydratase-Mangel","synonyms":["CARKD-Mangel"],"definition":"Eine seltene neurometabolische Erkrankung, die sich durch wiederholte Episoden von Entwicklungsrückschritten und Neurodegeneration im Säuglingsalter auszeichnet und häufig durch fiebrige Erkrankungen ausgelöst wird. Die Patienten präsentieren sich mit Lethargie, Hypotonie, Reizbarkeit, Gangataxie, Sprachverlust, Bewegungsstörungen, Krampfanfällen, Ophthalmoplegie und Hörverlust. Die Bildgebung des Gehirns zeigt eine generalisierte zerebrale Atrophie und bilaterale Basalganglienanomalien. In Zusammenhang mit der Erkrankung wurden ausgedehnte Hautläsionen, Kardiomyopathie und Panzytopenie berichtet. Der Zustand ist in den ersten Lebensjahren tödlich."},"es":{"name":"Deficiencia de NAD(P)HX deshidratasa","synonyms":["Deficiencia de CARKD"],"definition":"Es una enfermedad neurometabólica poco frecuente caracterizada por la aparición en la lactancia de episodios repetidos de regresión del desarrollo y neurodegeneración, a menudo desencadenados por enfermedades febriles. Los pacientes presentan letargia, hipotonía, irritabilidad, ataxia de la marcha, pérdida del habla, trastornos del movimiento, crisis epilépticas, oftalmoplejía y pérdida auditiva. La neuroimagen muestra atrofia cerebral generalizada y alteraciones bilaterales de los ganglios basales. Se ha descrito la asociación con lesiones cutáneas extensas, miocardiopatía y pancitopenia. La condición es fatal en los primeros años de vida."},"it":{"name":"Deficit di NAD(P)HX deidratasi","definition":"Si tratta di una malattia neurometabolica rara, che esordisce nella prima infanzia con episodi ripetuti di regressione dello sviluppo e degenerazione neurologica, spesso scatenati da malattie febbrili. I pazienti presentano letargia, ipotonia, irritabilità, andatura atassica, perdita del linguaggio, anomalie del movimento, crisi epilettiche, oftalmoplegia e sordità. Le neuroimmagini mostrano un'atrofia cerebrale generalizzata e anomalie bilaterali dei gangli basali. I pazienti possono presentare anche lesioni cutanee estese, cardiomiopatia e pancitopenia. La malattia è letale nei primi anni di vita."},"nl":{"name":"NAD(P)HX-dehydratasedeficiëntie","synonyms":["CARKD-deficiëntie"],"definition":"Een zeldzame neurometabole aandoening, gekarakteriseerd door infantiele aanvang van herhaaldelijke episodes van ontwikkelingsregressie en neurodegeneratie, vaak uitgelokt door febriele ziekte. Patiënten presenteren zich met lethargie, hypotonie, prikkelbaarheid, gangataxie, verlies van spraak, bewegingsstoornis, insulten, oftalmoplegie, en gehoorverlies. Beeldvorming van hersenen toont gegeneraliseerde cerebrale atrofie en bilaterale afwijkingen van basale ganglia. Associatie van omvangrijke laesies van huid, cardiomyopathie, en pancytopenie werd ook reeds gerapporteerd. De aandoening is fataal in het eerste levensjaar."},"pt":{"name":"Deficiência de NAD(P)HX desidratase"},"pl":{"name":"Niedobór dehydratazy NAD(P)HX","synonyms":["CARKD deficiency"]},"cs":{"name":"Deficit NAD(P)HX dehydratázy","synonyms":["Deficit CARKD"]},"uk":{"name":"Дефіцит дегідратази NAD(P)HX","synonyms":["Дефіцит серцево-судинної системи"],"definition":"A rare neurometabolic disease characterized by infantile onset of repeated episodes of developmental regression and neurodegeneration, often triggered by febrile illnesses. Patients present with lethargy, hypotonia, irritability, gait ataxia, loss of speech, movement disorder, seizures, ophthalmoplegia, and hearing loss. Brain imaging shows generalized cerebral atrophy and bilateral basal ganglia abnormalities. Extensive skin lesions, cardiomyopathy, and pancytopenia have been reported in association. The condition is fatal in the first years of life."},"zh":{"name":"NAD(P)HX脱水酶缺乏","synonyms":["CARKD基因缺陷"]},"tr":{"name":"NAD (P) HX dehidrataz eksikliği","synonyms":["CARKD eksikliği"]}},"xrefs":[{"source":"OMIM","code":"618321","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C5Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0034121","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C5193026","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":183500,"name":"Genetic neurodegenerative disease","classifications":[156]},{"orpha":68385,"name":"Neurometabolic disease","classifications":[156,181]},{"orpha":91088,"name":"Other metabolic disease","classifications":[150,156]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]}],"children":[],"genes":[{"symbol":"NAXD","name":"NAD(P)HX dehydratase","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"30576410[PMID]","hgnc":"25576","ensembl":"ENSG00000213995","omim":"615910","loci":["13q34"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Childhood","Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"30576410[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_30576410[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2026-01-12","source":"39822994[PMID]_36158054[PMID]_34161859[PMID]","terms":[{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0008066","label":"Abnormal blistering of the skin","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001903","label":"Anemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008972","label":"Decreased activity of mitochondrial respiratory chain","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002353","label":"EEG abnormality","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011227","label":"Elevated circulating C-reactive protein concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001288","label":"Gait disturbance","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011355","label":"Localized skin lesion","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003198","label":"Myopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002013","label":"Vomiting","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002134","label":"Abnormal basal ganglia morphology","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001251","label":"Ataxia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001638","label":"Cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000518","label":"Cataract","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030915","label":"Cerebellar edema","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000405","label":"Conductive hearing impairment","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001332","label":"Dystonia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0031956","label":"Elevated circulating aspartate aminotransferase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012819","label":"Myocarditis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000602","label":"Ophthalmoplegia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001876","label":"Pancytopenia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002209","label":"Sparse scalp hair","frequency":"Very rare (<4-1%)","criteria":null}]}}