Details of Disease

General Information of Disease (ID: DIS8RZP9)

Disease Name	Pyruvate dehydrogenase complex deficiency
Synonyms	deficiency of pyruvic dehydrogenase; PDHC; PDH; pyruvate dehydrogenase complex deficiency; Pyruvate Dehydrogenase Complex Deficiency; pyruvate dehydrogenase deficiency; pyruvate dehydrogenase complex deficiency disease; pyruvate decarboxylase deficiency
Disease Class	5C53: Inborn energy metabolism error
Definition	Pyruvate dehydrogenase deficiency (PDHD) is a rare neurometabolic disorder characterized by a wide range of clinical signs with metabolic and neurological components of varying severity. Manifestations range from often fatal, severe, neonatal lactic acidosis to later-onset neurological disorders. Six subtypes related to the affected subunit of the PDH complex have been recognized with significant clinical overlap: PDHD due to E1-alpha, E1-beta, E2 and E3 deficiency, PDHD due to E3-binding protein deficiency, and PDH phosphatase deficiency.
Disease Hierarchy	DISP5E0H: Inborn mitochondrial metabolism disorder DISOEVKS: Metabolic epilepsy DISSYRHC: Hereditary peripheral neuropathy DISFFYB2: Pyruvate metabolism disorder DISO5FAY: Inborn error of metabolism DISV24X3: Carbohydrate metabolism disorder DIS8RZP9: Pyruvate dehydrogenase complex deficiency
ICD Code	ICD-11 ICD-11: 5C53.02
Disease Identifiers	MONDO ID MONDO_0019169 MESH ID D015325 UMLS CUI C0034345 MedGen ID 19610 Orphanet ID 765 SNOMED CT ID 124593001

Drug-Interaction Atlas (DIA) of This Disease

Drug-Interaction Atlas (DIA)

This Disease is Treated as An Indication in 1 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Dichloroacetate	DMZ5Y1P	Phase 4	Small molecular drug	[1]
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Molecular Interaction Atlas (MIA) of This Disease

Molecular Interaction Atlas (MIA)

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
LONP1	TTM1VPZ	Strong	Genetic Variation	[2]
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This Disease Is Related to 1 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC9A6	DTN0JXW	Strong	Genetic Variation	[3]
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This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GSTZ1	DEQPEMB	moderate	Biomarker	[4]
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This Disease Is Related to 8 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
DLAT	OT9LBJVN	Strong	Biomarker	[5]
ECHS1	OTS0593S	Strong	Biomarker	[6]
LIPT1	OT2KCI00	Strong	Biomarker	[7]
PDHA2	OT9D9T2F	Strong	Genetic Variation	[8]
PDHB	OT2NHE5E	Strong	Genetic Variation	[9]
PDHX	OTG7O271	Strong	Genetic Variation	[8]
PDHA1	OTGEU8IK	Definitive	Biomarker	[10]
PDP1	OT82RTMT	Definitive	Biomarker	[11]
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⏷ Show the Full List of 8 DOT(s)

References

1	ClinicalTrials.gov (NCT02616484) Trial of Dichloroacetate in Pyruvate Dehydrogenase Complex Deficiency: (DCA/PDCD). U.S. National Institutes of Health.
2	Bi-allelic mutations of LONP1 encoding the mitochondrial LonP1 protease cause pyruvate dehydrogenase deficiency and profound neurodegeneration with progressive cerebellar atrophy. Hum Mol Genet. 2019 Jan 15;28(2):290-306. doi: 10.1093/hmg/ddy351.
3	Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.Epilepsia. 2015 May;56(5):707-16. doi: 10.1111/epi.12954. Epub 2015 Mar 25.
4	Personalized dosing of dichloroacetate using GSTZ1 clinical genotyping assay. Genet Test Mol Biomarkers. 2018 Apr;22(4):266-269.
5	Pyruvate dehydrogenase E2 deficiency: a potentially treatable cause of episodic dystonia.Eur J Paediatr Neurol. 2010 Jul;14(4):349-53. doi: 10.1016/j.ejpn.2009.11.001. Epub 2009 Dec 21.
6	Clinical and biochemical characterization of four patients with mutations in ECHS1.Orphanet J Rare Dis. 2015 Jun 18;10:79. doi: 10.1186/s13023-015-0290-1.
7	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.
8	Complex genetic findings in a female patient with pyruvate dehydrogenase complex deficiency: Null mutations in the PDHX gene associated with unusual expression of the testis-specific PDHA2 gene in her somatic cells.Gene. 2016 Oct 15;591(2):417-24. doi: 10.1016/j.gene.2016.06.041. Epub 2016 Jun 22.
9	Pyruvate dehydrogenase complex deficiency caused by ubiquitination and proteasome-mediated degradation of the E1 subunit.J Biol Chem. 2008 Jan 4;283(1):237-243. doi: 10.1074/jbc.M704748200. Epub 2007 Oct 8.
10	Pyruvate dehydrogenase complex deficiency and its relationship with epilepsy frequency--An overview.Epilepsy Res. 2015 Oct;116:40-52. doi: 10.1016/j.eplepsyres.2015.07.002. Epub 2015 Jul 8.
11	Increased pyruvate dehydrogenase activity in skeletal muscle of growth-restricted ovine fetuses.Am J Physiol Regul Integr Comp Physiol. 2019 Oct 1;317(4):R513-R520. doi: 10.1152/ajpregu.00106.2019. Epub 2019 Jul 17.