Hypermethioninemia is an excess of the
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha am ...
methionine
Methionine (symbol Met or M) () is an essential amino acid in humans. As the precursor of other amino acids such as cysteine and taurine, versatile compounds such as SAM-e, and the important antioxidant glutathione, methionine plays a critical ro ...
, in the blood. This condition can occur when methionine is not broken down properly in the body.
Presentation
Genetics
Hypermethioninemia can have different inheritance patterns. This condition is usually inherited in an
autosomal recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
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
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
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.
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 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 suffic ...
), which is important in many cellular processes.
* The ''MAT1A'' gene provides instructions for producing the enzyme
methionine adenosyltransferase. This enzyme converts methionine into a compound called
S-adenosylmethionine
''S''-Adenosyl methionine (SAM), also known under the commercial names of SAMe, SAM-e, or AdoMet, is a common cosubstrate involved in methyl group transfers, transsulfuration, and aminopropylation. Although these anabolic reactions occur throug ...
.
* The ''GNMT'' gene provides instructions for making the enzyme
glycine N-methyltransferase
In enzymology, a glycine N-methyltransferase () is an enzyme that catalyzes the chemical reaction
:S-adenosyl-L-methionine + glycine \rightleftharpoons S-adenosyl-L-homocysteine + sarcosine
Thus, the substrates of this enzyme are S-adenosyl met ...
. 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 is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In the b ...
. Homocysteine may be converted back to methionine or into another amino acid,
cysteine
Cysteine (symbol Cys or C; ) is a semiessential proteinogenic amino acid with the formula . The thiol side chain in cysteine often participates in enzymatic reactions as a nucleophile.
When present as a deprotonated catalytic residue, sometime ...
.
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.
Diagnosis
People with hypermethioninemia often do not show any symptoms. Some individuals with hypermethioninemia exhibit learning disabilities,
mental retardation
Intellectual disability (ID), also known as general learning disability in the United Kingdom and formerly mental retardation,Rosa's Law, Pub. L. 111-256124 Stat. 2643(2010). is a generalized neurodevelopmental disorder characterized by signific ...
, 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 or HCU is an inherited disorder of the metabolism of the amino acid methionine due to a deficiency of cystathionine beta synthase or methionine synthase. It is an inherited autosomal recessive trait, which means a child needs to inh ...
,
tyrosinemia
Tyrosinemia or tyrosinaemia is an error of metabolism, usually inborn, in which the body cannot effectively break down the amino acid tyrosine. Symptoms of untreated tyrosinemia include liver and kidney disturbances. Without treatment, tyrosinemi ...
and
galactosemia
Galactosemia (British galactosaemia, from Greek γαλακτόζη + αίμα, meaning galactose + blood, accumulation of galactose in blood) is a rare genetic metabolic disorder that affects an individual's ability to metabolize the sugar galacto ...
, which also involve the faulty breakdown of particular molecules. It can also result from
liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the sig ...
or excessive dietary intake of methionine from consuming large amounts of protein or a methionine-enriched infant formula.
Treatment
See also
*
List of amino acid metabolism disorders
Inborn errors of amino acid metabolism are metabolic disorders which impair the synthesis and degradation of amino acids.
Types
*Alkaptonuria
*Aspartylglucosaminuria
*Branched-chain keto acid dehydrogenase kinase deficiency
*Methylmalonic acidemi ...
References
External links
{{Amino acid metabolic pathology
Amino acid metabolism disorders
Autosomal recessive disorders