Details of Disease

General Information of Disease (ID: DIS8G1WP)

• Disease Name: 3-methylglutaconic aciduria
• Definition: A group of five inherited disorders caused by mutations in the AUH, DNAJC19, OPA3, and TAZ genes. The disorders are characterized by impairment in the function of mitochondria, resulting in the accumulation and excretion of 3-methylglutaconic acid, and the presence of 3-methylglutaric acid in the urine.
• Disease Hierarchy:
  DISCXXVK: Classic organic aciduria
  DIS8G1WP: 3-methylglutaconic aciduria
• Disease Identifiers:
  MONDO ID: MONDO_0017359
  MESH ID: C579867
  UMLS CUI: C3696376
  MedGen ID: 777186
  HPO ID: HP:0003535
  Orphanet ID: 289902
  SNOMED CT ID: 237950009

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 1 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AGK	TTJETQC	Strong	Biomarker	[1]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
DHCR7	DEL7GFA	Limited	Genetic Variation	[2]

This Disease Is Related to 12 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACADSB	OTDO6HBG	Limited	Biomarker	[2]
SERAC1	OTWH1ULQ	Limited	Genetic Variation	[3]
DNAJC19	OTLA1V91	moderate	Genetic Variation	[4]
ECHS1	OTS0593S	moderate	Biomarker	[5]
MICOS13	OTNNPM61	moderate	Genetic Variation	[4]
AUH	OT8VKBXX	Strong	Biomarker	[2]
CLPB	OT1I0IBK	Strong	Genetic Variation	[6]
HTRA2	OTC7616F	Strong	Biomarker	[7]
OPA3	OT6NDC1M	Strong	Biomarker	[8]
POLG	OTDUCT04	Strong	Genetic Variation	[9]
TIMM50	OTWJNUQL	Strong	Genetic Variation	[10]
TMEM70	OTLTKYXG	Strong	Genetic Variation	[11]

References

• [1] Bi-allelic CLPB mutations cause cataract, renal cysts, nephrocalcinosis and 3-methylglutaconic aciduria, a novel disorder of mitochondrial protein disaggregation.J Inherit Metab Dis. 2015 Mar;38(2):211-9. doi: 10.1007/s10545-015-9813-0. Epub 2015 Jan 18.
• [2] Genotype-based databases for variants causing rare diseases.Gene. 2014 Oct 15;550(1):136-40. doi: 10.1016/j.gene.2014.08.016. Epub 2014 Aug 8.
• [3] Identification of a novel splice site mutation in the SERAC1 gene responsible for the MEGDHEL syndrome.Mol Genet Genomic Med. 2019 Aug;7(8):e815. doi: 10.1002/mgg3.815. Epub 2019 Jun 28.
• [4] Mitochondrial hepato-encephalopathy due to deficiency of QIL1/MIC13 (C19orf70), a MICOS complex subunit. Eur J Hum Genet. 2016 Dec;24(12):1778-1782. doi: 10.1038/ejhg.2016.83. Epub 2016 Aug 3.
• [5] Clinical, biochemical, and genetic features of four patients with short-chain enoyl-CoA hydratase (ECHS1) deficiency.Am J Med Genet A. 2018 May;176(5):1115-1127. doi: 10.1002/ajmg.a.38658. Epub 2018 Mar 25.
• [6] Mitochondrial dysfunction, AMPK activation and peroxisomal metabolism: A coherent scenario for non-canonical 3-methylglutaconic acidurias.Biochimie. 2020 Jan;168:53-82. doi: 10.1016/j.biochi.2019.10.004. Epub 2019 Oct 15.
• [7] HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy-Report of 11 Patients.Neuropediatrics. 2018 Dec;49(6):373-378. doi: 10.1055/s-0038-1667345. Epub 2018 Aug 16.
• [8] Atypical presentation of Costeff syndrome-severe psychomotor involvement and electrical status epilepticus during slow wave sleep.Eur J Paediatr Neurol. 2015 Nov;19(6):733-6. doi: 10.1016/j.ejpn.2015.06.006. Epub 2015 Jul 9.
• [9] POLG mutation in a patient with cataracts, early-onset distal muscle weakness and atrophy, ovarian dysgenesis and 3-methylglutaconic aciduria.Gene. 2012 May 10;499(1):209-12. doi: 10.1016/j.gene.2012.02.034. Epub 2012 Mar 3.
• [10] Mutations in TIMM50 cause severe mitochondrial dysfunction by targeting key aspects of mitochondrial physiology.Hum Mutat. 2019 Oct;40(10):1700-1712. doi: 10.1002/humu.23779. Epub 2019 May 17.
• [11] Persistent pulmonary arterial hypertension in the newborn (PPHN): a frequent manifestation of TMEM70 defective patients.Mol Genet Metab. 2014 Mar;111(3):353-359. doi: 10.1016/j.ymgme.2014.01.001. Epub 2014 Jan 8.