Details of Disease

General Information of Disease (ID: DISZI1ZK)

Disease Name Lactic acidosis
Definition Metabolic acidosis characterized by the accumulation of lactate in the body. It is caused by tissue hypoxia.
Disease Hierarchy
DIS71G5H: Metabolic disorder
DISZI1ZK: Lactic acidosis
Disease Identifiers
MONDO ID
MONDO_0006040
MESH ID
D000140
UMLS CUI
C0001125
MedGen ID
1717
HPO ID
HP:0003128
SNOMED CT ID
91273001

Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)
This Disease Is Related to 3 DTT Molecule(s)
Gene Name DTT ID Evidence Level Mode of Inheritance REF
MGAM TTXWASR moderate Biomarker [1]
PLAT TTXAGYU Strong Therapeutic [2]
SLC47A1 TTMHCGA Strong Biomarker [3]
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This Disease Is Related to 1 DTP Molecule(s)
Gene Name DTP ID Evidence Level Mode of Inheritance REF
SLC25A3 DTCRIWV moderate Biomarker [4]
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This Disease Is Related to 2 DME Molecule(s)
Gene Name DME ID Evidence Level Mode of Inheritance REF
GSTZ1 DEQPEMB Strong Genetic Variation [5]
WARS2 DEPTKBQ Strong Genetic Variation [6]
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This Disease Is Related to 43 DOT Molecule(s)
Gene Name DOT ID Evidence Level Mode of Inheritance REF
COQ9 OTM2T1FI Limited Genetic Variation [7]
DLD OT378CU9 Limited Biomarker [8]
EARS2 OTNCJKY7 Limited Genetic Variation [9]
ELAC2 OTY3BOF6 Limited Genetic Variation [10]
HADHA OTO557N2 Limited Biomarker [11]
IBA57 OT9SPG2X Limited Biomarker [12]
ISCU OTSW6DQP Limited Genetic Variation [13]
ND1 OTCLGIXV Limited Genetic Variation [14]
NDUFS4 OTJKUYEE Limited Biomarker [15]
RMND1 OT7I6RBT Limited Genetic Variation [16]
RNPS1 OT7G4COD Limited Biomarker [17]
SCO2 OTJQQDRS Limited Genetic Variation [18]
SRSF2 OTVDHO6U Limited Altered Expression [17]
SUCLA2 OTMZD4PW Limited Altered Expression [19]
EXOSC9 OTFKB37F moderate Genetic Variation [20]
MRPS14 OTA8H3LB moderate Genetic Variation [21]
ND4 OT4RQVAA moderate Genetic Variation [22]
NDUFB11 OTFG5777 moderate Genetic Variation [23]
PDHA1 OTGEU8IK moderate Genetic Variation [24]
SURF1 OTAINRSS moderate Biomarker [25]
TRMT10C OT1L8Q48 moderate Genetic Variation [26]
ACAD9 OT4HITJ6 Strong Genetic Variation [27]
ARRDC4 OTINJ0FX Strong Altered Expression [28]
ATAD3A OTWF6HBP Strong Biomarker [29]
ATP5F1E OTMPLAIS Strong Genetic Variation [30]
BCS1L OT5PY5CY Strong Genetic Variation [31]
COX1 OTG3O9BN Strong Genetic Variation [32]
CYTB OTAHB98A Strong Genetic Variation [33]
DNM1L OTXK1Q1G Strong Biomarker [34]
ECHS1 OTS0593S Strong Biomarker [35]
KARS1 OT0EU4SV Strong Biomarker [36]
LIPT1 OT2KCI00 Strong Genetic Variation [37]
MRPS22 OTIVNAJL Strong Genetic Variation [38]
MTO1 OT7HCZ1D Strong Biomarker [39]
NDUFA5 OTR848KZ Strong Biomarker [40]
PC OT6O0V51 Strong Biomarker [41]
PDP1 OT82RTMT Strong Genetic Variation [17]
POLG OTDUCT04 Strong Genetic Variation [42]
RRM2B OTE8GBUR Strong Biomarker [43]
TANGO2 OTT9UI89 Strong CausalMutation [44]
TMEM70 OTLTKYXG Strong Genetic Variation [45]
FBXL4 OTZECCIQ Definitive Genetic Variation [46]
TFAM OTXXV5V7 Definitive Altered Expression [47]
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⏷ Show the Full List of 43 DOT(s)

References

1 Coumarin-based Scaffold as -glucosidase Inhibitory Activity: Implication for the Development of Potent Antidiabetic Agents.Mini Rev Med Chem. 2020;20(2):134-151. doi: 10.2174/1389557519666190925162536.
2 Airway tissue plasminogen activator prevents acute mortality due to lethal sulfur mustard inhalation.Toxicol Sci. 2015 Jan;143(1):178-84. doi: 10.1093/toxsci/kfu225. Epub 2014 Oct 20.
3 Loss of multidrug and toxin extrusion 1 (MATE1) is associated with metformin-induced lactic acidosis.Br J Pharmacol. 2012 Jun;166(3):1183-91. doi: 10.1111/j.1476-5381.2012.01853.x.
4 Mitochondrial phosphate-carrier deficiency: a novel disorder of oxidative phosphorylation. Am J Hum Genet. 2007 Mar;80(3):478-84. doi: 10.1086/511788. Epub 2007 Jan 10.
5 Polymorphisms in the human glutathione transferase zeta promoter.Pharmacogenet Genomics. 2006 May;16(5):307-13. doi: 10.1097/01.fpc.0000205000.07054.b3.
6 Expanding the Phenotype: Neurodevelopmental Disorder, Mitochondrial, With Abnormal Movements and Lactic Acidosis, With or Without Seizures (NEMMLAS) due to WARS2 Biallelic Variants, Encoding Mitochondrial Tryptophanyl-tRNA Synthase.J Child Neurol. 2019 Oct;34(12):778-781. doi: 10.1177/0883073819854604. Epub 2019 Jul 8.
7 Fatal neonatal encephalopathy and lactic acidosis caused by a homozygous loss-of-function variant in COQ9.Eur J Hum Genet. 2016 Mar;24(3):450-4. doi: 10.1038/ejhg.2015.133. Epub 2015 Jun 17.
8 Leigh disease with deficiency of lipoamide dehydrogenase: treatment failure with dichloroacetate.Pediatr Neurol. 1996 Jan;14(1):69-71. doi: 10.1016/0887-8994(96)00005-7.
9 EARS2 mutations cause fatal neonatal lactic acidosis, recurrent hypoglycemia and agenesis of corpus callosum.Metab Brain Dis. 2016 Jun;31(3):717-21. doi: 10.1007/s11011-016-9793-2. Epub 2016 Jan 16.
10 Mutations in ELAC2 associated with hypertrophic cardiomyopathy impair mitochondrial tRNA 3'-end processing.Hum Mutat. 2019 Oct;40(10):1731-1748. doi: 10.1002/humu.23777. Epub 2019 Jun 18.
11 Pathology of skeletal muscle and impaired respiratory chain function in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency with the G1528C mutation.Neuromuscul Disord. 1996 Oct;6(5):327-37. doi: 10.1016/0960-8966(96)00352-5.
12 Novel mutations in IBA57 are associated with leukodystrophy and variable clinical phenotypes.J Neurol. 2017 Jan;264(1):102-111. doi: 10.1007/s00415-016-8312-z. Epub 2016 Oct 26.
13 The defective splicing caused by the ISCU intron mutation in patients with myopathy with lactic acidosis is repressed by PTBP1 but can be derepressed by IGF2BP1.Hum Mutat. 2012 Mar;33(3):467-70. doi: 10.1002/humu.22002. Epub 2011 Dec 29.
14 Sporadic intragenic inversion of the mitochondrial DNA MTND1 gene causing fatal infantile lactic acidosis.Pediatr Res. 2006 Mar;59(3):440-4. doi: 10.1203/01.pdr.0000198771.78290.c4.
15 Targeting NAD(+) Metabolism as Interventions for Mitochondrial Disease.Sci Rep. 2019 Feb 28;9(1):3073. doi: 10.1038/s41598-019-39419-4.
16 RMND1-Related Leukoencephalopathy With Temporal Lobe Cysts and Hearing Loss-Another Mendelian Mimicker of Congenital Cytomegalovirus Infection.Pediatr Neurol. 2017 Jan;66:59-62. doi: 10.1016/j.pediatrneurol.2016.09.003. Epub 2016 Sep 13.
17 The SR protein SC35 is responsible for aberrant splicing of the E1alpha pyruvate dehydrogenase mRNA in a case of mental retardation with lactic acidosis.Mol Cell Biol. 2005 Apr;25(8):3286-94. doi: 10.1128/MCB.25.8.3286-3294.2005.
18 A homozygous mutation in the SCO2 gene causes a spinal muscular atrophy like presentation with stridor and respiratory insufficiency.Eur J Paediatr Neurol. 2010 May;14(3):253-60. doi: 10.1016/j.ejpn.2009.09.008. Epub 2009 Oct 29.
19 SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness.Brain. 2007 Mar;130(Pt 3):862-74. doi: 10.1093/brain/awl389. Epub 2007 Feb 14.
20 Expanded PCH1D phenotype linked to EXOSC9 mutation.Eur J Med Genet. 2020 Jan;63(1):103622. doi: 10.1016/j.ejmg.2019.01.012. Epub 2019 Jan 25.
21 A variant in MRPS14 (uS14m) causes perinatal hypertrophic cardiomyopathy with neonatal lactic acidosis, growth retardation, dysmorphic features and neurological involvement. Hum Mol Genet. 2019 Feb 15;28(4):639-649. doi: 10.1093/hmg/ddy374.
22 The expanding clinical spectrum of mitochondrial diseases.Brain Dev. 1993 Jan-Feb;15(1):1-22. doi: 10.1016/0387-7604(93)90002-p.
23 A novel mutation in NDUFB11 unveils a new clinical phenotype associated with lactic acidosis and sideroblastic anemia. Clin Genet. 2017 Mar;91(3):441-447. doi: 10.1111/cge.12790. Epub 2016 May 25.
24 Enzymatic testing sensitivity, variability and practical diagnostic algorithm for pyruvate dehydrogenase complex (PDC) deficiency.Mol Genet Metab. 2017 Nov;122(3):61-66. doi: 10.1016/j.ymgme.2017.09.001. Epub 2017 Sep 8.
25 SURF1 deficiency causes demyelinating Charcot-Marie-Tooth disease. Neurology. 2013 Oct 22;81(17):1523-30. doi: 10.1212/WNL.0b013e3182a4a518. Epub 2013 Sep 11.
26 Recessive Mutations in TRMT10C Cause Defects in Mitochondrial RNA Processing and Multiple Respiratory Chain Deficiencies. Am J Hum Genet. 2016 May 5;98(5):993-1000. doi: 10.1016/j.ajhg.2016.03.010. Epub 2016 Apr 28.
27 Clinical, biochemical and genetic spectrum of 70 patients with ACAD9 deficiency: is riboflavin supplementation effective?.Orphanet J Rare Dis. 2018 Jul 19;13(1):120. doi: 10.1186/s13023-018-0784-8.
28 Lactic acidosis triggers starvation response with paradoxical induction of TXNIP through MondoA.PLoS Genet. 2010 Sep 2;6(9):e1001093. doi: 10.1371/journal.pgen.1001093.
29 Recurrent De Novo and Biallelic Variation of ATAD3A, Encoding a Mitochondrial Membrane Protein, Results in Distinct Neurological Syndromes. Am J Hum Genet. 2016 Oct 6;99(4):831-845. doi: 10.1016/j.ajhg.2016.08.007. Epub 2016 Sep 15.
30 Defective mitochondrial ATPase due to rare mtDNA m.8969G>A mutation-causing lactic acidosis, intellectual disability, and poor growth.Neurogenetics. 2018 Jan;19(1):49-53. doi: 10.1007/s10048-018-0537-9. Epub 2018 Jan 19.
31 A novel mutation in BCS1L associated with deafness, tubulopathy, growth retardation and microcephaly. Eur J Pediatr. 2016 Apr;175(4):517-25. doi: 10.1007/s00431-015-2661-y. Epub 2015 Nov 13.
32 Mutations in C12orf62, a factor that couples COX I synthesis with cytochrome c oxidase assembly, cause fatal neonatal lactic acidosis. Am J Hum Genet. 2012 Jan 13;90(1):142-51. doi: 10.1016/j.ajhg.2011.11.027.
33 Impact of the mitochondrial genetic background in complex III deficiency.PLoS One. 2010 Sep 17;5(9):e12801. doi: 10.1371/journal.pone.0012801.
34 A lethal defect of mitochondrial and peroxisomal fission. N Engl J Med. 2007 Apr 26;356(17):1736-41. doi: 10.1056/NEJMoa064436.
35 A lethal neonatal phenotype of mitochondrial short-chain enoyl-CoA hydratase-1 deficiency.Clin Genet. 2017 Apr;91(4):629-633. doi: 10.1111/cge.12891. Epub 2016 Nov 30.
36 Inhibition of mitochondrial translation in fibroblasts from a patient expressing the KARS p.(Pro228Leu) variant and presenting with sensorineural deafness, developmental delay, and lactic acidosis.Hum Mutat. 2018 Dec;39(12):2047-2059. doi: 10.1002/humu.23657. Epub 2018 Oct 3.
37 LIPT1 deficiency presenting as early infantile epileptic encephalopathy, Leigh disease, and secondary pyruvate dehydrogenase complex deficiency.Am J Med Genet A. 2018 May;176(5):1184-1189. doi: 10.1002/ajmg.a.38654.
38 MRPS22 mutation causes fatal neonatal lactic acidosis with brain and heart abnormalities.Neurogenetics. 2015 Jul;16(3):237-40. doi: 10.1007/s10048-015-0440-6. Epub 2015 Feb 10.
39 The genotypic and phenotypic spectrum of MTO1 deficiency.Mol Genet Metab. 2018 Jan;123(1):28-42. doi: 10.1016/j.ymgme.2017.11.003. Epub 2017 Nov 15.
40 Nuclear DNA origin of mitochondrial complex I deficiency in fatal infantile lactic acidosis evidenced by transnuclear complementation of cultured fibroblasts.J Clin Invest. 1999 Jul;104(1):83-92. doi: 10.1172/JCI6184.
41 Intron retention and frameshift mutations result in severe pyruvate carboxylase deficiency in two male siblings. Hum Mutat. 2002 Jul;20(1):48-56. doi: 10.1002/humu.10093.
42 Two novel POLG mutations causing hepatic mitochondrial DNA depletion with recurrent hypoketotic hypoglycaemia and fatal liver dysfunction.Dig Liver Dis. 2009 Jul;41(7):494-9. doi: 10.1016/j.dld.2008.11.013. Epub 2009 Feb 4.
43 A novel homozygous RRM2B missense mutation in association with severe mtDNA depletion.Neuromuscul Disord. 2009 Feb;19(2):147-50. doi: 10.1016/j.nmd.2008.11.014. Epub 2009 Jan 12.
44 Recurrent Muscle Weakness with Rhabdomyolysis, Metabolic Crises, and Cardiac Arrhythmia Due to Bi-allelic TANGO2 Mutations. Am J Hum Genet. 2016 Feb 4;98(2):347-57. doi: 10.1016/j.ajhg.2015.12.008. Epub 2016 Jan 21.
45 Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation.Arch Dis Child. 2010 Apr;95(4):296-301. doi: 10.1136/adc.2009.168096.
46 FBXL4 defects are common in patients with congenital lactic acidemia and encephalomyopathic mitochondrial DNA depletion syndrome.Clin Genet. 2017 Apr;91(4):634-639. doi: 10.1111/cge.12894. Epub 2017 Jan 5.
47 Lactic Acidosis Promotes Mitochondrial Biogenesis in Lung Adenocarcinoma Cells, Supporting Proliferation Under Normoxia or Survival Under Hypoxia.Front Oncol. 2019 Oct 17;9:1053. doi: 10.3389/fonc.2019.01053. eCollection 2019.