{"orpha":746,"name":"Mitochondrial trifunctional protein deficiency","type":"Disease","group":"Disorder","status":"active","flags":[],"synonyms":["TFP deficiency","TFPD"],"definition":"A rare disorder of fatty acid oxidation characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy..","note":null,"url":"https://raremap.alftech.space/d/ORPHA-746/","orphanet_url":"https://www.orpha.net/en/disease/detail/746","names":{"fr":{"name":"Déficit en protéine trifonctionnelle mitochondriale","synonyms":["Déficit en TFP","TFPD"],"definition":"Le déficit en protéine trifonctionnelle mitochondriale (DPTFM) est un trouble de l'oxydation des acides gras caractérisé par un large spectre clinique. Celui-ci peut s'étendre de manifestations néonatales sévères incluant une cardiomyopathie, une hypoglycémie, une acidose métabolique, une myopathie et une neuropathie squelettiques, une hépatopathie et un décès, à un phénotype léger comprenant une polyneuropathie périphérique, des épisodes de rhabdomyolyse et une rétinopathie pigmentaire."},"de":{"name":"Defekt des mitochondrialen trifunktionalen Proteins","synonyms":["MTP (mitochondriales trifunktionales Protein)-Mangel","TFP-Mangel","TFPD"],"definition":"Der Mangel des Mitochondrialen trifunktionalen Proteins (TFP; TFP-Mangel) ist eine Störung der Fettsäureoxidation. Das klinische Spektrum ist breit und reicht von schweren neonatalen Formen mit Kardiomyopathie, Hypoglykämie, metabolischer Azidose, Skelettmyopathie, Neuropathie, Leberfunktionsstörung und frühem Tod bis zu einem milden Phänotyp mit peripherer Polyneuropathie, episodischer Rhabdomyolyse und Pigment-Retinopathie."},"es":{"name":"Deficiencia de proteína trifuncional mitocondrial","synonyms":["Deficiencia de TFP","TFPD"],"definition":"Es una alteración de la oxidación de los ácidos grasos caracterizada por un amplio espectro clínico que va desde manifestaciones neonatales graves como la miocardiopatía, la hipoglucemia, la acidosis metabólica, la miopatía esquelética y la neuropatía, la hepatopatía y la muerte, hasta un fenotipo leve con polineuropatía periférica, rabdomiólisis y retinopatía pigmentaria."},"it":{"name":"Deficit della proteina trifunzionale mitocondriale","synonyms":["Deficit di TFP","TFPD"],"definition":"Il deficit della proteina trifunzionale mitocondriale (TFP; TFPD) è un difetto dell'ossidazione degli acidi grassi caratterizzato da un ampio quadro clinico che varia dai segni neonatali gravi, come la cardiomiopatia, l'ipoglicemia, l'acidosi metabolica, la miopatia dei muscoli scheletrici, la neuropatia, l'epatopatia e la morte, ad un fenotipo lieve con polineuropatia periferica, rabdomiolisi e retinite pigmentosa."},"nl":{"name":"Deficiëntie van mitochondriaal trifunctioneel proteïne","synonyms":["MTP-deficiëntie","MTPD","TFP-deficiëntie","TFPD"],"definition":"Een zeldzame stoornis van de vetzuuroxidatie, gekarakteriseerd door een breed klinisch spectrum gaande van ernstige neonatale manifestaties zoals cardiomyopathie, hypoglycemie, metabole acidose, skeletmyopathie, neuropathie, leverziekte, en overlijden tot een mild fenotype met perifere polyneuropathie, episodische rabdomyolyse, en pigmentretinopathie."},"pt":{"name":"Deficiência de proteína trifuncional mitocondrial"},"pl":{"name":"Niedobór mitochondrialnego trójfunkcyjnego kompleksu białkowego","synonyms":["Niedobór TFP","TFPD"]},"cs":{"name":"Deficit mitochondriálního trifunkčního proteinu","synonyms":["Deficit TFP","TFPD"]},"uk":{"name":"Дефіцит мітохондріального трифункціонального білка","synonyms":["Дефіцит ТФП","TFPD"],"definition":"A rare disorder of fatty acid oxidation characterized by a wide clinical spectrum ranging from severe neonatal manifestations including cardiomyopathy, hypoglycemia, metabolic acidosis, skeletal myopathy and neuropathy, liver disease and death to a mild phenotype with peripheral polyneuropathy, episodic rhabdomyolysis and pigmentary retinopathy.."},"zh":{"name":"线粒体三功能蛋白缺乏症","synonyms":["TFP缺乏"]},"tr":{"name":"Mitokondriyal üç işlevli protein eksikliği","synonyms":["TFPD","TFP eksikliği"]}},"xrefs":[{"source":"OMIM","code":"609015","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"OMIM","code":"620300","qualifier":"BTNT","icd_relation":null,"validated":true},{"source":"ICD-10","code":"E71.3","qualifier":"NTBT","icd_relation":"attributed","validated":true},{"source":"ICD-11","code":"5C52.01","qualifier":"NTBT","icd_relation":"index","validated":true,"icd11_uri":"1018083832"},{"source":"MONDO","code":"0012172","qualifier":"E","icd_relation":null,"validated":true},{"source":"MeSH","code":"C566945","qualifier":"E","icd_relation":null,"validated":true},{"source":"UMLS","code":"C1969443","qualifier":"E","icd_relation":null,"validated":true},{"source":"GARD","code":"3684","qualifier":"E","icd_relation":null,"validated":true},{"source":"MedDRA","code":"10077949","qualifier":"E","icd_relation":null,"validated":true}],"associations":[],"incoming_associations":[],"preferential_parent":{"orpha":68367,"name":"Rare inborn error of metabolism"},"parents":[{"orpha":309115,"name":"Disorder of fatty acid oxidation and ketogenesis","classifications":[150,156]},{"orpha":217591,"name":"Fatty acid oxidation and ketogenesis disorder with hypertrophic cardiomyopathy","classifications":[146,156,233]},{"orpha":206966,"name":"Mitochondrial myopathy","classifications":[156,181]},{"orpha":207018,"name":"Rare hereditary metabolic disease with peripheral neuropathy","classifications":[156,181]}],"children":[],"genes":[{"symbol":"HADHA","name":"hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit alpha","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"4801","ensembl":"ENSG00000084754","omim":"600890","loci":["2p23.3"]},{"symbol":"HADHB","name":"hydroxyacyl-CoA dehydrogenase trifunctional multienzyme complex subunit beta","gene_type":"gene with protein product","association":"Disease-causing germline mutation(s) in","status":"Assessed","source":null,"hgnc":"4803","ensembl":"ENSG00000138029","omim":"143450","loci":["2p23.3"]}],"genes_via_subtypes":[],"inheritance":["Autosomal recessive"],"onset":["Infancy","Neonatal"],"prevalence":[{"type":"Cases/families","qualification":"Case(s)","class":null,"value":100.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22000755[PMID]"},{"type":"Point prevalence","qualification":"Class only","class":"Unknown","value":0.0,"area":"Worldwide","status":"Validated","source":"ORPHANET_22000755[PMID]"},{"type":"Point prevalence","qualification":"Value and class","class":"1-9 / 100 000","value":1.0,"area":"Europe","status":"Validated","source":"European Medicines Agency 2015[OTHER]"}],"phenotypes":{"validation_status":"y","online":"y","validation_date":"2019-01-18","source":"28515471[PMID]_28649548[PMID]_19880769[PMID]_19699128[PMID]_12838198[PMID]_28685493[PMID]_875757[PMID]_1401059[PMID]_1445348[PMID]","terms":[{"hpo":"HP:0001284","label":"Areflexia","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003546","label":"Exercise intolerance","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0003201","label":"Rhabdomyolysis","frequency":"Very frequent (99-80%)","criteria":null},{"hpo":"HP:0001638","label":"Cardiomyopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0100626","label":"Chronic hepatic failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001635","label":"Congestive heart failure","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011808","label":"Decreased patellar reflex","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003551","label":"Difficulty climbing stairs","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0006555","label":"Diffuse hepatic steatosis","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001531","label":"Failure to thrive in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0008872","label":"Feeding difficulties in infancy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002901","label":"Hypocalcemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001985","label":"Hypoketotic hypoglycemia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001252","label":"Hypotonia","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001712","label":"Left ventricular hypertrophy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001254","label":"Lethargy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0007340","label":"Lower limb muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003394","label":"Muscle spasm","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0001324","label":"Muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009830","label":"Peripheral neuropathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0002033","label":"Poor suck","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0009063","label":"Progressive distal muscle weakness","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0003756","label":"Skeletal myopathy","frequency":"Frequent (79-30%)","criteria":null},{"hpo":"HP:0011675","label":"Arrhythmia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003487","label":"Babinski sign","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001396","label":"Cholestasis","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001259","label":"Coma","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008110","label":"Equinovarus deformity","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0008138","label":"Equinus calcaneus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002359","label":"Frequent falls","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003324","label":"Generalized muscle weakness","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000829","label":"Hypoparathyroidism","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001653","label":"Mitral regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001270","label":"Motor delay","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0003326","label":"Myalgia","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001761","label":"Pes cavus","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0000580","label":"Pigmentary retinopathy","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002878","label":"Respiratory failure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0002093","label":"Respiratory insufficiency","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0001250","label":"Seizure","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0030051","label":"Tip-toe gait","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0005180","label":"Tricuspid regurgitation","frequency":"Occasional (29-5%)","criteria":null},{"hpo":"HP:0007067","label":"Distal peripheral sensory neuropathy","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0002476","label":"Primitive reflex","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0025145","label":"Rigors","frequency":"Very rare (<4-1%)","criteria":null},{"hpo":"HP:0007141","label":"Sensorimotor neuropathy","frequency":"Very rare (<4-1%)","criteria":null}]}}