| H01022 | |
| H number | H01022 |
| Name | Diseases of the tricarboxylic acid cycle |
| Description | Diseases of the tricarboxylic acid cycle (TCA cycle) constitute a group of rare human diseases that affect core mitochondrial metabolism. The Fumarase deficiency is caused by impairment of the fumarate hydratase enzyme. The symptoms of the disorder include developmental delay, severe mental retardation, language impairment, seizures and dysmorphic facial features. The succinate dehydrogenase deficiency [DS:H02005] affects mitochondrial complex II, which links the TCA cycle with the electron transport chain. The phenotype is highly variable and can include Leigh syndrome, leukodystrophy, cardiomyopathy and mental and motor skill deterioration. The alpha-ketoglutarate dehydrogenase deficiency is extremely rare and characterised by encephalopathy and hyperlactatemia resulting in death in early childhood. |
| Category | Inherited metabolic disorder |
| Network | nt06031 Citrate cycle and pyruvate metabolism |
| Gene | (FMRD) FH [HSA:2271] [KO:K01679] (MC2DN1) SDHA [HSA:6389] [KO:K00234] (OGDHD) OGDH [HSA:4967] [KO:K00164] |
| Pathogen | - |
| Env factor | - |
| Carcinogen | - |
| Drug | - |
| Comment | Succinate dehydrogenase deficiency is also included in mitochondrial respiratory chain deficiencies. [DS:H00473] |
| Other DBs | ICD-11: 5C53.1 ICD-10: E88.8 MeSH: C538191 C565375 C536582 OMIM: 606812 252011 203740 |
| Reference | PMID:21714867 AUTHORS Smith AC, Robinson AJ TITLE A metabolic model of the mitochondrion and its use in modelling diseases of the tricarboxylic acid cycle. JOURNAL BMC Syst Biol 5:102 (2011) DOI:10.1186/1752-0509-5-102 PMID:9300800 AUTHORS Rustin P, Bourgeron T, Parfait B, Chretien D, Munnich A, Rotig A TITLE Inborn errors of the Krebs cycle: a group of unusual mitochondrial diseases in human. JOURNAL Biochim Biophys Acta 1361:185-97 (1997) DOI:10.1016/S0925-4439(97)00035-5 PMID:8200987 (FMRD) AUTHORS Bourgeron T, Chretien D, Poggi-Bach J, Doonan S, Rabier D, Letouze P, Munnich A, Rotig A, Landrieu P, Rustin P TITLE Mutation of the fumarase gene in two siblings with progressive encephalopathy and fumarase deficiency. JOURNAL J Clin Invest 93:2514-8 (1994) DOI:10.1172/JCI117261 PMID:7550341 (MC2DN1) AUTHORS Bourgeron T, Rustin P, Chretien D, Birch-Machin M, Bourgeois M, Viegas-Pequignot E, Munnich A, Rotig A TITLE Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. JOURNAL Nat Genet 11:144-9 (1995) DOI:10.1038/ng1095-144 PMID:32383294 (OGDHD) AUTHORS Yap ZY, Strucinska K, Matsuzaki S, Lee S, Si Y, Humphries K, Tarnopolsky MA, Yoon WH TITLE A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease. JOURNAL J Inherit Metab Dis 44:388-400 (2021) DOI:10.1002/jimd.12248 |