Klinische FragestellungPyruvat-Dehydrogenase-Defizienz, Differentialdiagnose

NGS +

Seltene neurometabolische Störung, breites Spektrum klinischer Anzeichen, metabolische + neurologische Komponenten, unterschiedlicher Schweregrad; oft tödliche neonatale Laktatazidose oder später einsetzende neurologische Störungen; 6 Subtypen, die mit der betroffenen Untereinheit des PDH-Komplexes zusammenhängen, signifikante klinische Überlappung: PDHD aufgrund von E1-alpha-, E1-beta-, E2- und E3-Mangel, PDHD aufgrund eines Mangels an E3-bindendem Protein, PDH-Phosphatase-Mangel

• Alias: Ahornsirup-Krankheit, E3-defiziente (DLD)
• Alias: Dihydro-Lipoamid-Dehydrogenase-Mangel (DLD)
• Alias: Dihydrolipoamide dehydrogenase deficiency (DLD)
• 3-hydroxyisobutryl-CoA hydrolase deficiency (HIBCH)
• Anemia, sideroblastic, 3, pyridoxine-refractory (GLRX5)
• CODAS (cerebral, ocular, dental, auricular, skeletal anomalies) syndrome (LONP1)
• Charcot-Marie-Tooth disease, XLD, 6 (PDK3)
• Combined D-2- + L-2-hydroxyglutaric aciduria (SLC25A1)
• Combined oxidative phosphorylation deficiency 28 (SLC25A26)
• Encephalopathy, neonatal severe, with lactic acidosis + brain abnormalities (LIPT2)
• HARP syndrome (PANK2)
• Hyperglycinemia, lactic acidosis + seizures (LIAS)
• Lacticacidemia due to PDX1 deficiency (PDHX)
• Lipoyltransferase 1 deficiency (LIPT1)
• Microcephaly, Amish type (SLC24A19)
• Mitochondrial DNA depletion syndrome, encephalomyopathic type (FBXL4)
• Mitochondrial short-chain enoyl-CoA hydratase 1 deficiency (ECHS1)
• Multiple mitochondrial dysfunctions syndrome 1 (NFU1)
• Multiple mitochondrial dysfunctions syndrome 3 (IBA57)
• Multiple mitochondrial dysfunctions syndrome 4 (ISCA2)
• Multiple mitochondrial dysfunctions syndrome 5 (ISCA1)
• Multiple mitochondrial dysfunctions syndrome 6 (PMPCB)
• Multiple mitochondrial dysfunctions syndrome with hyperglycinemia (BOLA3)
• Myasthenic syndrome, congenital, 23, presynaptic (SLC25A1)
• Neurodegeneration with brain iron accumulation 1 (PANK2)
• Pyruvate dehydrogenase E1-alpha deficiency (PDHA1)
• Pyruvate dehydrogenase E1-beta deficiency (PDHB)
• Pyruvate dehydrogenase E2 deficiency (DLAT)
• Pyruvate dehydrogenase phosphatase deficiency (PDP1)
• Spasticity, childhood-onset, with hyperglycinemia (GLRX5)
• Thiamine metabolism dysfunction syndrome 4, progressive polyneuropathy type (SLC25A19)
• Thiamine metabolism dysfunction syndrome 5, episodic encephalopathy type (TPK1)
• Thiamine metabolism dysfunction syndrome, biotin/thiamine-responsive encephalopathy type2 (SLC19A3)
• Thiamine-responsive megaloblastic anemia syndrome (SLC19A2)