Hypermethioninemia is an excess of the amino acid

Amino acid

Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 methionine

Methionine

Methionine is an α-amino acid with the chemical formula HO2CCHCH2CH2SCH3. This essential amino acid is classified as nonpolar. This amino-acid is coded by the codon AUG, also known as the initiation codon, since it indicates mRNA's coding region where translation into protein...

, in the blood. This condition can occur when methionine is not broken down properly in the body.

Diagnosis

People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit learning disabilities, mental retardation

Mental retardation

Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...

, 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

Homocystinuria

Homocystinuria, also known as cystathionine beta synthase deficiency or CBS deficiency, is an inherited disorder of the metabolism of the amino acid methionine, often involving cystathionine beta synthase...

, tyrosinemia

Tyrosinemia

Tyrosinemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms include liver and kidney disturbances and mental retardation...

 and galactosemia

Galactosemia

Galactosemia is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galactose properly. Although the sugar lactose can metabolize to galactose, galactosemia is not related to and should not be confused with lactose intolerance...

, which also involve the faulty breakdown of particular molecules. It can also result from liver disease

Liver disease

Liver disease is a broad term describing any single number of diseases affecting the liver.-Diseases:* Hepatitis, inflammation of the liver, caused mainly by various viruses but also by some poisons , autoimmunity or hereditary conditions...

 or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.

Pathophysiology

Inherited hypermethioninemia that is not associated with other metabolic disorders can be caused by shortages in the enzymes that break down methionine. These enzymes are produced from the MAT1A, GNMT and AHCY genes. The reactions involved in metabolizing methionine help supply some of the amino acids needed for protein production. These reactions are also involved in transferring methyl groups, consisting of a carbon atom and three hydrogen atoms, from one molecule to another (transmethylation

Transmethylation

Transmethylation is a biologically important organic chemical reaction in which a methyl group is transferred from one compound to another.An example of transmethylation is the recovery of methionine from homocysteine. In order to sustain sufficient reaction rates during metabolic stress, this...

), which is important in many cellular processes.

• The MAT1A gene provides instructions for producing the enzyme methionine adenosyltransferase
  Methionine adenosyltransferase
  Methionine adenosyltransferase is an enzyme which catalyses the synthesis of S-adenosylmethionine from methionine and ATP.-External links:...
  
  . This enzyme converts methionine into a compound called S-adenosylmethionine.
• The GNMT gene provides instructions for making the enzyme glycine N-methyltransferase
  Glycine N-methyltransferase
  In enzymology, a glycine N-methyltransferase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are S-adenosyl methionine and glycine, whereas its two products are S-adenosylhomocysteine and sarcosine....
  
  . This enzyme starts the next step in the process, converting S-adenosylmethionine to a compound called S-adenosyl homocysteine.
• The AHCY gene provides instructions for producing the enzyme S-adenosylhomocysteine hydrolase. This enzyme converts the S-adenosyl homocysteine into the compound homocysteine
  Homocysteine
  Homocysteine is a non-protein amino acid with the formula HSCH2CH2CHCO2H. It is a homologue of the amino acid cysteine, differing by an additional methylene group. It is biosynthesized from methionine by the removal of its terminal Cε methyl group...
  
  . Homocysteine may be converted back to methionine or into another amino acid, cysteine
  Cysteine
  Cysteine is an α-amino acid with the chemical formula HO2CCHCH2SH. It is a non-essential amino acid, which means that it is biosynthesized in humans. Its codons are UGU and UGC. The side chain on cysteine is thiol, which is polar and thus cysteine is usually classified as a hydrophilic amino acid...
  
  .

A deficiency of any of these enzymes results in a buildup of methionine in the body, and may cause signs and symptoms related to hypermethioninemia.

Inheritance

Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Hypermethioninemia is occasionally inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. In these cases, an affected person usually has one parent with the condition.

General references

• National Library of Medicine. Hypermethioninemia