KEGG   DISEASE: H01022Help
Entry
H01022                      Disease                                

Name
Diseases of the tricarboxylic acid cycle, including:
Fumarase (FH) deficiency;
Succinate dehydrogenase (SDH) deficiency;
Alpha-ketoglutarate dehydrogenase (AKGDH) deficiency
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 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
Metabolic disease
BRITE hierarchy
Pathway
Citrate cycle (TCA cycle)
Gene
(FH) FH [HSA:2271] [KO:K01679]
(SDH) SDHA [HSA:6389] [KO:K00234]
(AKGDH) OGDH [HSA:4967] [KO:K00164]
Marker
(FH) Fumarate [CPD:C00122] , 2-Oxoglutarate [CPD:C00026] (urine) Lactate [CPD:C00186] (cerebrospinal fluid)
(SDH) Lactate (blood plasma) 2-Oxoglutarate and Succinate [CPD:C00042] (urine in some cases) Succinate accumulation (brain)
(AKGDH) Oxoglutarate [CPD:C00026] Lactate
Comment
Succinate dehydrogenase deficiency is also included in mitochondrial respiratory chain deficiencies. [DS:H00473]
Other DBs
Reference
  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)
Reference
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)

» Japanese version

DBGET integrated database retrieval system