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Hepatic methionine adenosyltransferase deficiency

MedGen UID:
75700
Concept ID:
C0268621
Disease or Syndrome
Synonyms: Deficiency of methionine adenosyltransferase; Isolated Persistent Hypermethioninemia; MAT I/III DEFICIENCY; Methionine adenosyltransferase deficiency
SNOMED CT: Methionine adenosyltransferase deficiency (57835009); Deficiency of methionine adenosyltransferase (124283007); Hepatic methionine adenosyltransferase deficiency (57835009); MAT deficiency (57835009)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): MAT1A (10q22.3)
 
Monarch Initiative: MONDO:0009607
OMIM®: 250850
Orphanet: ORPHA168598

Definition

Methionine adenosyltransferase deficiency is an inborn error of metabolism resulting in isolated hypermethioninemia. Most patients have no clinical abnormalities, although some with the autosomal recessive form have have neurologic abnormalities (Mudd et al., 2003; Kim et al., 2016). [from OMIM]

Additional description

From MedlinePlus Genetics
Hypermethioninemia is an excess of a particular protein building block (amino acid), called methionine, in the blood. This condition can occur when methionine is not broken down (metabolized) properly in the body.

People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit intellectual disability and other neurological problems; delays in motor skills such as standing or walking; sluggishness; muscle weakness; liver problems; unusual facial features; and their breath, sweat, or urine may have a smell resembling boiled cabbage.

Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia, and galactosemia, which also involve the faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula. The condition is called primary hypermethioninemia when it is not associated with other metabolic disorders or excess methionine in the diet.  https://medlineplus.gov/genetics/condition/hypermethioninemia

Clinical features

From HPO
Dystonic disorder
MedGen UID:
3940
Concept ID:
C0013421
Sign or Symptom
An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Hyperreflexia
MedGen UID:
57738
Concept ID:
C0151889
Finding
Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.
CNS demyelination
MedGen UID:
137898
Concept ID:
C0338474
Disease or Syndrome
A loss of myelin from nerve fibers in the central nervous system.
Peripheral demyelination
MedGen UID:
451074
Concept ID:
C0878575
Pathologic Function
A loss of myelin from the internode regions along myelinated nerve fibers of the peripheral nervous system.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hypermethioninemia
MedGen UID:
887708
Concept ID:
C4048705
Disease or Syndrome
An increased concentration of methionine in the blood.
Halitosis
MedGen UID:
42326
Concept ID:
C0018520
Sign or Symptom
Noticeably unpleasant odors exhaled in breathing.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHepatic methionine adenosyltransferase deficiency
Follow this link to review classifications for Hepatic methionine adenosyltransferase deficiency in Orphanet.

Professional guidelines

PubMed

Keller R, Chrastina P, Pavlíková M, Gouveia S, Ribes A, Kölker S, Blom HJ, Baumgartner MR, Bártl J, Dionisi-Vici C, Gleich F, Morris AA, Kožich V, Huemer M; individual contributors of the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD), Barić I, Ben-Omran T, Blasco-Alonso J, Bueno Delgado MA, Carducci C, Cassanello M, Cerone R, Couce ML, Crushell E, Delgado Pecellin C, Dulin E, Espada M, Ferino G, Fingerhut R, Garcia Jimenez I, Gonzalez Gallego I, González-Irazabal Y, Gramer G, Juan Fita MJ, Karg E, Klein J, Konstantopoulou V, la Marca G, Leão Teles E, Leuzzi V, Lilliu F, Lopez RM, Lund AM, Mayne P, Meavilla S, Moat SJ, Okun JG, Pasquini E, Pedron-Giner CC, Racz GZ, Ruiz Gomez MA, Vilarinho L, Yahyaoui R, Zerjav Tansek M, Zetterström RH, Zeyda M
J Inherit Metab Dis 2019 Jan;42(1):128-139. doi: 10.1002/jimd.12034. PMID: 30740731
Tran C, Bonafé L, Nuoffer JM, Rieger J, Berger MM
Clin Nutr 2018 Aug;37(4):1114-1120. Epub 2017 Jul 25 doi: 10.1016/j.clnu.2017.07.013. PMID: 28779878
Barić I, Staufner C, Augoustides-Savvopoulou P, Chien YH, Dobbelaere D, Grünert SC, Opladen T, Petković Ramadža D, Rakić B, Wedell A, Blom HJ
J Inherit Metab Dis 2017 Jan;40(1):5-20. Epub 2016 Sep 26 doi: 10.1007/s10545-016-9972-7. PMID: 27671891Free PMC Article

Curated

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Methionine +/- Elevated Homocysteine, Homocystinuria (Cystathionine beta-synthase deficiency), 2021

American College of Medical Genetics and Genomics, Algorithm, Elevated Methionine +/- Elevated Homocysteine, 2021

Recent clinical studies

Etiology

Gahl WA, Bernardini I, Finkelstein JD, Tangerman A, Martin JJ, Blom HJ, Mullen KD, Mudd SH
J Clin Invest 1988 Feb;81(2):390-7. doi: 10.1172/JCI113331. PMID: 3339126Free PMC Article

Diagnosis

Chou JY
Pharmacol Ther 2000 Jan;85(1):1-9. doi: 10.1016/s0163-7258(99)00047-9. PMID: 10674710
Gahl WA, Finkelstein JD, Mullen KD, Bernardini I, Martin JJ, Backlund P, Ishak KG, Hoofnagle JH, Mudd SH
Am J Hum Genet 1987 Jan;40(1):39-49. PMID: 3812486Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2021
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated Methionine +/- Elevated Homocysteine, Homocystinuria (Cystathionine beta-synthase deficiency), 2021
    • ACMG Algorithm, 2021
      American College of Medical Genetics and Genomics, Algorithm, Elevated Methionine +/- Elevated Homocysteine, 2021

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