Details of Disease

General Information of Disease (ID: DIS4SI69)

• Disease Name: Methionine adenosyltransferase deficiency
• Synonyms: Mat I/III deficiency; methionine adenosyltransferase I/III deficiency; hypermethioninemia, isolated persistent; MAT deficiency; brain demyelination due to methionine adenosyltransferase deficiency; isolated persistent hypermethioninemia; MAT I/III deficiency; methionine adenosyltransferase deficiency, autosomal recessive; hypermethioninemia, persistent, autosomal dominant, due to methionine adenosyltransferase I/III deficiency; methionine adenosyltransferase deficiency
• Definition: Hypermethioninemia due to methionine adenosyltransferase deficiency is a very rare metabolic disorder resulting in isolated hepatic hypermethioninemia that is usually benign due to partial inactivation of enzyme activity. Rarely patients have been found to have an odd odor or neurological disorders such as brain demyelination.
• Disease Hierarchy:
  DISUP794: Inborn disorder of methionine cycle and sulfur amino acid metabolism
  DIS4SI69: Methionine adenosyltransferase deficiency
• Disease Identifiers:
  MONDO ID: MONDO_0009607
  MESH ID: C564683
  UMLS CUI: C0268621
  OMIM ID: 250850
  MedGen ID: 75700
  Orphanet ID: 168598
  SNOMED CT ID: 124283007

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 4 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ADK	TTL732K	Limited	Genetic Variation	[1]
ACAT1	TTK3C21	Strong	Genetic Variation	[2]
AHCY	TTE2KUJ	Strong	Biomarker	[3]
MAT2A	TTSMPXQ	Strong	Genetic Variation	[2]

This Disease Is Related to 2 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
MAT1A	DEQ6NC9	Definitive	Autosomal recessive	[4]
MAT1A	DEQ6NC9	Definitive	Biomarker	[5]

This Disease Is Related to 5 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ALG1	OTVXPA9E	Strong	Genetic Variation	[6]
GNMT	OT0O2OQO	Strong	Biomarker	[7]
FAH	OTGZA1YR	Definitive	Biomarker	[8]
MAT1A	OTK72E4F	Definitive	Autosomal recessive	[4]
MCCD1	OTLS95WO	Definitive	Genetic Variation	[9]

References

• [1] Whole exome sequencing revealed mutations in FBXL4, UNC80, and ADK in Thai patients with severe intellectual disabilities.Gene. 2019 May 15;696:21-27. doi: 10.1016/j.gene.2019.01.049. Epub 2019 Feb 14.
• [2] MAT2A mutations predispose individuals to thoracic aortic aneurysms.Am J Hum Genet. 2015 Jan 8;96(1):170-7. doi: 10.1016/j.ajhg.2014.11.015. Epub 2014 Dec 31.
• [3] Abnormal Hypermethylation at Imprinting Control Regions in Patients with S-Adenosylhomocysteine Hydrolase (AHCY) Deficiency. PLoS One. 2016 Mar 14;11(3):e0151261. doi: 10.1371/journal.pone.0151261. eCollection 2016.
• [4] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [5] Neonatal methionine adenosyltransferase I/III deficiency with abnormal signal intensity in the central tegmental tract.Brain Dev. 2019 Apr;41(4):382-388. doi: 10.1016/j.braindev.2018.10.010. Epub 2018 Oct 30.
• [6] Demyelination of the brain is associated with methionine adenosyltransferase I/III deficiency. J Clin Invest. 1996 Aug 15;98(4):1021-7. doi: 10.1172/JCI118862.
• [7] Mutations in human glycine N-methyltransferase give insights into its role in methionine metabolism. Hum Genet. 2002 Jan;110(1):68-74. doi: 10.1007/s00439-001-0648-4. Epub 2001 Dec 7.
• [8] Hypermethioninemias of genetic and non-genetic origin: A review.Am J Med Genet C Semin Med Genet. 2011 Feb 15;157C(1):3-32. doi: 10.1002/ajmg.c.30293. Epub 2011 Feb 9.
• [9] Expanded Newborn Screening for Inborn Errors of Metabolism by Tandem Mass Spectrometry in Suzhou, China: Disease Spectrum, Prevalence, Genetic Characteristics in a Chinese Population.Front Genet. 2019 Oct 29;10:1052. doi: 10.3389/fgene.2019.01052. eCollection 2019.