{"orpha":401874,"name":"Multiple mitochondrial dysfunctions syndrome type 2","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["BOLA3 deficiency","MMDS2"],"definition":"A rare mitochondrial disease characterized by infantile onset of severe regression after a period of normal development, epileptic encephalopathy, hypotonia, movement disorder, cardiomyopathy, hyperglycinemia, and lactic acidosis. Optic atrophy may also be present. Brain imaging findings are highly variable and include white matter abnormalities. The disease is typically fatal in infancy.","note":null,"url":"https://raremap.alftech.space/d/ORPHA-401874/","orphanet_url":"https://www.orpha.net/en/disease/detail/401874","names":{"fr":{"name":"Syndrome de dysfonctionnements mitochondriaux multiples type 2","synonyms":["Déficit en BOLA3"],"definition":"Maladie mitochondriale rare caractérisée par une régression sévère à début infantile après une période de développement normale, une encéphalopathie épileptique, une hypotonie, des mouvements anormaux, une cardiomyopathie, une hyperglycinémie et une acidose lactique. Une atrophie optique peut également être présente. Les résultats de l'imagerie cérébrale sont très variables, mais des anomalies de la substance blanche sont observées. La maladie est létale dans la petite enfance."},"de":{"name":"Syndrom der multiplen mitochondrialen Dysfunktionen Typ 2","synonyms":["BOLA3-Mangel"],"definition":"Eine seltene mitochondriale Erkrankung mit schwerer Regression im Kindesalter nach normaler Entwicklung, epileptischer Enzephalopathie, Hypotonie, Bewegungsstörungen, Kardiomyopathie, Hyperglykämie und Laktatazidose. Eine Optikusatrophie kann ebenfalls auftreten. Die zerebralen Bildgebungsbefunde sind sehr variabel und umfassen Anomalien der weißen Substanz. Die Krankheit verläuft in der Regel im Säuglingsalter tödlich."},"es":{"name":"Síndrome de disfunción mitocondrial múltiple tipo 2","synonyms":["Deficiencia de BOLA3"],"definition":"Es una enfermedad mitocondrial poco frecuente caracterizada por el inicio en la lactancia de grave regresión después de un período de desarrollo normal, encefalopatía epiléptica, hipotonía, trastornos del movimiento, miocardiopatía, hiperglicinemia y acidosis láctica. También puede haber atrofia óptica. Los hallazgos de la neuroimagen son altamente variables e incluyen anomalías de la sustancia blanca. La enfermedad suele ser mortal en la lactancia."},"it":{"name":"Sindrome da disfunzione mitocondriale multipla tipo 2","synonyms":["Deficit di BOLA3"],"definition":"Si tratta di una malattia mitocondriale rara, che esordisce nella prima infanzia con grave regressione che fa seguito ad un periodo di sviluppo normale, encefalopatia epilettica, ipotonia, anomalie del movimento, cardiomiopatia, iperglicinemia e acidosi lattica. Può associarsi ad atrofia ottica. Le neuroimmagini evidenziano anomalie molto variabili, che comprendono le anomalie della sostanza bianca. In genere la malattia è letale nella prima infanzia."},"nl":{"name":"Multipele mitochondriale disfuncties-syndroom type 2","synonyms":["BOLA3-deficiëntie"],"definition":"Een zeldzame mitochondriale aandoening, gekenmerkt door infantiele aanvang van ernstige regressie na een periode van normale ontwikkeling, epileptische encefalopathie, hypotonie, bewegingsstoornis, cardiomyopathie, hyperglycinemie, en lactaatacidose. Opticusatrofie kan ook aanwezig zijn. Bevindingen van beeldvorming van hersenen zijn zeer variabel en omvatten onder meer afwijkingen van witte stof. De ziekte is doorgaans fataal in de zuigelingentijd."},"pt":{"name":"Síndrome de disfunção mitocondrial múltipla, forma fatal tipo 2"},"pl":{"name":"Zespół śmiertelnej mnogiej dysfunkcji mitochondriów typu 2","synonyms":["Niedobór BOLA3"]},"cs":{"name":"Syndrom fatálních mnohočetných mitochondriálních dysfunkcí, typ 2","synonyms":["Deficit BOLA3"]},"uk":{"name":"Синдром множинних мітохондріальних дисфункцій, тип 2","synonyms":["Дефіцит BOLA3","MMDS2"],"definition":"A rare mitochondrial disease characterized by infantile onset of severe regression after a period of normal development, epileptic encephalopathy, hypotonia, movement disorder, cardiomyopathy, hyperglycinemia, and lactic acidosis. Optic atrophy may also be present. Brain imaging findings are highly variable and include white matter abnormalities. The disease is typically fatal in infancy."},"zh":{"name":"多发性线粒体功能障碍综合征2型","synonyms":["BOLA3缺陷"]},"tr":{"name":"Çoklu mitokondriyal disfonksiyon sendromu tip 2","synonyms":["MMDS2","BOLA3 eksikliği"]}},"xrefs":[{"source":"OMIM","code":"614299","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":"0013675","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C3280378","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":289573,"name":"Multiple mitochondrial dysfunctions syndrome","classifications":[150,156,181]}],"children":[],"genes":[{"symbol":"BOLA3","name":"bolA family member 3","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":"24334290[PMID]_24777537[PMID]","hgnc":"24415","ensembl":"ENSG00000163170","omim":"613183","loci":["2p13.1"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":6.0,"area":"Worldwide","status":"Validated","source":"24777537[PMID]_21944046[PMID]_24334290[PMID]_22562699[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"<1 / 1 000 000","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_24777537[PMID]_21944046[PMID]_24334290[PMID]_22562699[PMID]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2026-01-21","source":"34440194[PMID]_30302924[PMID]","terms":[{"hpo":"HP:0011400","label":"Abnormal CNS myelination","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:0002928","label":"Decreased activity of the pyruvate dehydrogenase complex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002376","label":"Developmental regression","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0200134","label":"Epileptic encephalopathy","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:0001639","label":"Hypertrophic cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002151","label":"Increased circulating lactate concentration","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001257","label":"Spasticity","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001272","label":"Cerebellar atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002059","label":"Cerebral atrophy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001644","label":"Dilated cardiomyopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0034659","label":"Elevated urine tiglylglycine level","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002240","label":"Hepatomegaly","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002154","label":"Hyperglycinemia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003108","label":"Hyperglycinuria","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0500230","label":"Increased CSF glycine concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002490","label":"Increased CSF lactate","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003542","label":"Increased circulating pyruvate concentration","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001942","label":"Metabolic acidosis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001336","label":"Myoclonus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000639","label":"Nystagmus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null}]}}