IllnessPyruvatdehydrogenase deficiency, differential diagnosis

NGS +

Rare neurometabolic disorder, wide range of clinical signs, metabolic + neurological components, varying severity; often fatal neonatal lactic acidosis or later-onset neurological disorders; 6 subtypes related to affected subunit of PDH complex, significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, PDH phosphatase deficiency

• 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)