{"orpha":363424,"name":"Multiple mitochondrial dysfunctions syndrome type 3","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["IBA57 deficiency","MMDS3"],"definition":"A rare neurometabolic disease, due to a lipoic acid biosynthesis defect, with a highly variable phenotype, typically characterized by early-onset acute or subacute developmental delay or regression frequently associated with feeding difficulties. Clinical severity is variable and may range from mild cases which present a later onset with slow neurological deterioration and general improvement over time to severe cases with clinical signs since birth and leading to early death. Associated manifestations include hypotonia, vision loss, respiratory failure, seizures, and intellectual disability. Brain magnetic resonance imaging frequently shows cavitating leukoencephalopathy with lesions in the periventricular/central white matter and parieto-occiîtal lobes.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-363424/","orphanet_url":"https://www.orpha.net/en/disease/detail/363424","names":{"fr":{"name":"Syndrome de dysfonctionnements mitochondriaux multiples type 3","synonyms":["Déficit en IBA57"],"definition":"Maladie neurométabolique rare due à un défaut de biosynthèse de l'acide lipoïque, dont le phénotype est très inconstant, typiquement caractérisé par l'apparition précoce d'un type sévère ou très sévère de retard ou de régression du développement, fréquemment associés à des difficultés à s'alimenter. Sur le plan clinique, la gravité varie entre des cas légers à début tardif se manifestant par une détérioration neurologique lente et une amélioration générale au fil du temps, et des cas graves avec les signes cliniques apparaissant à la naissance et conduisant à un décès précoce. Hypotonie, perte de la vision, insuffisance respiratoire, convulsions et déficience intellectuelle font partie des manifestations associées. L'imagerie par résonance magnétique du cerveau met fréquemment en évidence une leuco-encéphalopathie cavitaire et des lésions de la substance blanche périventriculaire/centrale et des lobes pariétal et occipital."},"de":{"name":"Syndrom der multiplen mitochondrialen Dysfunktionen Typ 3","synonyms":["IBA57-Mangel"],"definition":"Eine seltene neurometabolische Erkrankung, die auf einem Liponsäure-Biosynthesedefekt beruht, mit einem sehr variablen Phänotyp, der typischerweise durch eine früh einsetzende akute oder subakute Entwicklungsverzögerung oder -rückbildung gekennzeichnet ist, die häufig mit Fütterungsproblemen einhergeht. Der klinische Schweregrad ist variabel und kann von milden Fällen, die einen späteren Beginn mit langsamer neurologischer Verschlechterung und allgemeiner Verbesserung im Laufe der Zeit aufweisen, bis hin zu schweren Fällen mit klinischen Anzeichen seit der Geburt reichen und zum frühen Tod führen. Zu den assoziierten Manifestationen gehören Hypotonie, Sehverlust, Atemversagen, Krampfanfälle und intellektuelle Entwicklungsstörungen. Die Magnetresonanztomographie des Gehirns zeigt häufig eine kavitierende Leukoenzephalopathie mit Läsionen in der periventrikulären/zentralen weißen Substanz und den parieto-okzipitalen Lappen."},"es":{"name":"Síndrome de disfunción mitocondrial múltiple tipo 3","synonyms":["Deficiencia en IBA57"],"definition":"Es una enfermedad neurometabólica poco frecuente debida a un defecto de la biosíntesis del ácido lipoico. Posee un fenotipo altamente variable caracterizado, por lo general, por un retraso o una regresión temprana, aguda o subaguda, del desarrollo psicomotor asociado con frecuencia a dificultades en la alimentación. La gravedad clínica es variable y puede ir desde casos leves que presentan un inicio tardío con un deterioro neurológico lento y una mejora general con el tiempo, hasta casos graves con signos clínicos desde el nacimiento que conducen a muerte prematura. Otras manifestaciones asociadas incluyen hipotonía, pérdida de visión, insuficiencia respiratoria, crisis epilépticas y discapacidad intelectual. La resonancia magnética cerebral muestra, con frecuencia leucoencefalopatía cavitada con lesiones en la sustancia blanca periventricular/ central y en el lóbulo parieto-occipital."},"it":{"name":"Sindrome da disfunzioni mitocondriali multiple tipo 3","synonyms":["Deficit di IBA57","Sindrome da disfunzione mitocondriale multipla letale, tipo 3"],"definition":"Si tratta di una malattia neurometabolica rara, causata da un difetto della biosintesi dell'acido lipoico. Il quadro clinico è molto variabile e di solito è caratterizzato da ritardo acuto o subacuto o regressione dello sviluppo, spesso associati a difficoltà di alimentazione. La gravità è variabile e va dalle forme più lievi (a esordio più tardivo e con un lento deterioramento neurologico e un generale miglioramento nel tempo) alle forme più gravi, nelle quali i segni clinici sono congeniti ed esitano nella morte precoce. I pazienti presentano ipotonia, cecità, insufficienza respiratoria, crisi epilettiche e disabilità intellettiva. Spesso la risonanza magnetica del cervello evidenzia leucoencefalopatia cavitaria con lesioni della sostanza bianca periventricolare/centrale e dei lobi parieto-occipitali."},"nl":{"name":"Multipele mitochondriale disfuncties-syndroom type 3","synonyms":["IBA57-deficiëntie"],"definition":"Een zeldzame neurometabole ziekte door een defect van de biosynthese van liponzuur, met een zeer variabel fenotype, doorgaans gekenmerkt door vroege aanvang van acute of subacute ontwikkelingsachterstand of -regressie frequent geassocieerd met voedingsproblemen. De klinische ernst varieert en kan gaan van milde gevallen die een latere aanvang met trage neurologische aftakeling en mettertijd algemene verbetering vertonen, tot ernstige gevallen met klinische verschijnselen vanaf de geboorte en vroeg overlijden tot gevolg. Geassocieerde manifestaties zijn onder meer hypotonie, verlies van gezichtsvermogen, respiratoir falen, insulten, en intellectuele achterstand. Beeldvorming van de hersenen met magnetische resonantie toont vaak holtevormende leuko-encefalopathie met letsels in de periventriculaire/centrale witte stof en pariëto-occipitale kwabben."},"pt":{"name":"Síndrome de hipotonia – atrofia cerebral - hiperglicinémia"},"pl":{"name":"Zespół hipotonii, atrofii mózgu i hiperglicynemii","synonyms":["Śmiertelny zespół złożonej dysfunkcji mitochondrialnej typu 3","Wrodzone zaburzenie glikozylacji typu IIm"],"definition":"Rzadka choroba neurometaboliczna związana z defektem biosyntezy kwasu liponowego, o bardzo zmiennym fenotypie, zwykle charakteryzująca się ostrym lub podostrym opóźnieniem lub regresem rozwoju o wczesnym początku, często powiązaną z trudnościami w karmieniu. Nasilenie objawów klinicznych jest zmienne i może obejmować spektrum od łagodnych przypadków o późniejszym początku, z powolnym pogarszaniem się stanu neurologicznego i ogólną poprawą w miarę upływu czasu, do ciężkich przypadków z objawami klinicznymi od urodzenia, które prowadzą do przedwczesnej śmierci. Objawy towarzyszące obejmują hipotonię, utratę wzroku, niewydolność oddechową, drgawki i niepełnosprawność intelektualną. Rezonans magnetyczny mózgu często wykazuje leukoencefalopatię kawitacyjną ze zmianami w okołokomorowej/centralnej istocie białej oraz płatach ciemieniowo-potylicznych."},"cs":{"name":"Syndrom fatální mnohočetné mitochondriální dysfunkce, typ 3","synonyms":["Deficit IBA57"]},"uk":{"name":"Синдром множинної мітохондріальної дисфункції, тип 3","synonyms":["Дефіцит IBA57","MMDS3"],"definition":"A rare neurometabolic disease, due to a lipoic acid biosynthesis defect, with a highly variable phenotype, typically characterized by early-onset acute or subacute developmental delay or regression frequently associated with feeding difficulties. Clinical severity is variable and may range from mild cases which present a later onset with slow neurological deterioration and general improvement over time to severe cases with clinical signs since birth and leading to early death. Associated manifestations include hypotonia, vision loss, respiratory failure, seizures, and intellectual disability. Brain magnetic resonance imaging frequently shows cavitating leukoencephalopathy with lesions in the periventricular/central white matter and parieto-occiîtal lobes."},"zh":{"name":"多发性线粒体功能障碍综合征3型","synonyms":["IBA57缺乏"],"definition":"本病是一种由于硫辛酸生物合成缺陷所致的罕见神经代谢疾病，具有高度可变的表型，典型特征为早发急性或亚急性发育延迟或退化，通常与喂养困难有关。临床严重程度是可变的，范围可从轻至重度，轻度病例发病较晚，随时间推移出现缓慢的神经系统恶化和整体改善，严重病例从出生起就有临床症状，早期即可死亡。本病的相关表现包括张力减退、视力丧失、呼吸衰竭、癫痫发作和智力障碍。MRI成像经常显示空洞性白质脑病，损害位于脑室周围/中央白质和顶枕叶。"},"tr":{"name":"Çoklu mitokondriyal disfonksiyon sendromu tip 3","synonyms":["MMDS3","IBA57 eksikliği"]}},"xrefs":[{"source":"OMIM","code":"615330","qualifier":"E","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E88.8","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C53.2Y","qualifier":"NTBT","icd_relation":"attributed","validated":true,"icd11_uri":"null"},{"source":"MONDO","code":"0014132","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3809165","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":98006,"name":"Rare neurologic disease"},"parents":[{"orpha":289573,"name":"Multiple mitochondrial dysfunctions syndrome","classifications":[150,156,181]}],"children":[],"genes":[{"symbol":"IBA57","name":"iron-sulfur cluster assembly factor IBA57","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"23462291[PMID]","hgnc":"27302","ensembl":"ENSG00000181873","omim":"615316","loci":["1q42.13"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":2.0,"area":"Worldwide","status":"Validated","source":"23462291[PMID]"},{"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":"2026-01-29","source":"34440194[PMID]_36360281[PMID]_38923322[PMID]","terms":[{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0033369","label":"Cavitating leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011923","label":"Decreased activity of mitochondrial complex I","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008314","label":"Decreased activity of mitochondrial complex II","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001263","label":"Global developmental delay","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002154","label":"Hyperglycinemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0500230","label":"Increased CSF glycine concentration","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:0001249","label":"Intellectual disability","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0034392","label":"Joint contracture","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002415","label":"Leukodystrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0030891","label":"Periventricular white matter hyperintensities","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001561","label":"Polyhydramnios","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0033725","label":"Thin corpus callosum","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0000505","label":"Visual impairment","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0005949","label":"Apneic episodes in infancy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008347","label":"Decreased activity of mitochondrial complex IV","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0012707","label":"Elevated brain lactate level by MRS","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003128","label":"Lactic acidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000252","label":"Microcephaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000648","label":"Optic atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002126","label":"Polymicrogyria","frequency":"Occasional (29-5%)","criteria":null}]}}