{"orpha":569274,"name":"Multiple mitochondrial dysfunctions syndrome type 5","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["ISCA1 deficiency","MMDS5"],"definition":"A rare mitochondrial disease characterized by early infantile onset of progressive neurological deterioration with seizures, spasticity, and lack of psychomotor development. Brain imaging shows severe leukodystrophy and abnormalities of neuronal migration. Lactic acidosis is common. The disease is usually fatal in early childhood.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-569274/","orphanet_url":"https://www.orpha.net/en/disease/detail/569274","names":{"fr":{"name":"Syndrome de dysfonctionnements mitochondriaux multiples type 5","synonyms":["Déficit en ISCA1"],"definition":"Maladie mitochondriale rare caractérisée par une détérioration neurologique progressive se manifestant par l'apparition précoce, au cours de la petite enfance, de crises convulsives, d'une spasticité et d'une absence de développement psychomoteur. L'imagerie cérébrale montre une leucodystrophie sévère et des anomalies de la migration neuronale. L'acidose lactique est fréquente. La maladie est généralement fatale dans la petite enfance."},"de":{"name":"Syndrom der multiplen mitochondrialen Dysfunktionen Typ 5","synonyms":["ISCA1-Defizienz","ISCA1-Mangel","MMDS5"],"definition":"Eine seltene mitochondriale Erkrankung, die sich durch eine im frühen Kindesalter einsetzende progressive neurologische Verschlechterung mit Krampfanfällen, Spastizität und mangelnder psychomotorischer Entwicklung auszeichnet. Die Bildgebung des Gehirns zeigt schwere Leukodystrophie und Anomalien der neuronalen Migration. Eine Laktatazidose ist häufig. Die Krankheit verläuft in der Regel in der frühen Kindheit tödlich."},"es":{"name":"Síndrome de disfunción mitocondrial múltiple tipo 5","synonyms":["Deficiencia de ISCA1","MMDS5"],"definition":"Es una enfermedad mitocondrial poco frecuente caracterizada por un inicio precoz durante el periodo de lactancia de afectación neurológica progresiva con crisis, espasticidad y ausencia de desarrollo psicomotor. Las neuroimágenes muestran leucodistrofia grave y alteraciones de la migración neuronal. La acidosis láctica es común. La enfermedad suele ser mortal en la primera infancia."},"it":{"name":"Sindrome da disfunzioni mitocondriali multiple tipo 5","synonyms":["MMDS5","Deficit di ISCA1"]},"nl":{"name":"Multipele mitochondriale disfuncties-syndroom type 5","synonyms":["ISCA1-deficiëntie","MMDS5"],"definition":"Een zeldzame mitochondriale aandoening, gekenmerkt door vroeg infantiel optreden van progressieve neurologische achteruitgang met insulten, spasticiteit, en gebrek aan psychomotorische ontwikkeling. Beeldvorming van hersenen toont ernstige leukodystrofie en afwijkingen van neuronale migratie. Lactaatacidose is gangbaar. De ziekte is meestal fataal in de vroege kindertijd."},"pt":{"name":"Síndrome de disfunção mitocondrial múltipla tipo 5","definition":"Doença mitocondrial rara caracterizada por início infantil precoce de deterioração neurológica progressiva com convulsões, espasticidade e atraso do desenvolvimento psicomotor. Os exames de neuroimagem cerebral demonstram leucodistrofia grave e anomalias da migração neuronal. É comum existir acidose láctica. A doença é geralmente fatal na primeira infância."},"pl":{"name":"Zespół mnogich dysfunkcji mitochondrialnych, typu 5","synonyms":["ISCA1 deficiency","MMDS5"]},"cs":{"name":"Syndrom mnohočetné mitochondriální dysfunkce, typ 5","synonyms":["ISCA1 deficiency","MMDS5"]},"uk":{"name":"Синдром множинних мітохондріальних дисфункцій, тип 5","synonyms":["Дефіцит ISCA1","MMDS5"],"definition":"A rare mitochondrial disease characterized by early infantile onset of progressive neurological deterioration with seizures, spasticity, and lack of psychomotor development. Brain imaging shows severe leukodystrophy and abnormalities of neuronal migration. Lactic acidosis is common. The disease is usually fatal in early childhood."},"zh":{"name":"多线粒体功能障碍综合征5型","synonyms":["ISCA1基因缺陷"]},"tr":{"name":"Çoklu mitokondriyal disfonksiyon sendromu tip 5","synonyms":["MMDS5","ISCA1 eksikliği"]}},"xrefs":[{"source":"OMIM","code":"617613","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.21","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"MONDO","code":"0033282","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C4539919","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":289573,"name":"Multiple mitochondrial dysfunctions syndrome","classifications":[150,156,181]},{"orpha":182070,"name":"Rare neurodegenerative disease","classifications":[181]}],"children":[],"genes":[{"symbol":"ISCA1","name":"iron-sulfur cluster assembly 1","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"28356563[PMID]","hgnc":"28660","ensembl":"ENSG00000135070","omim":"611006","loci":["9q21.33"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"29767723[PMID]_30105122[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_29767723[PMID]_30105122[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2026-02-04","source":"30105122[PMID]_31580634[PMID]_34440194[PMID]","terms":[{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001302","label":"Pachygyria","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002119","label":"Ventriculomegaly","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0002500","label":"Abnormal cerebral white matter morphology","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0012707","label":"Elevated brain lactate level by MRS","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000365","label":"Hearing impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001347","label":"Hyperreflexia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003236","label":"Elevated circulating creatine kinase concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030215","label":"Inappropriate crying","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000580","label":"Pigmentary retinopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000253","label":"Progressive microcephaly","frequency":"Occasional (29-5%)","criteria":null}]}}