Hypermethioninemia
Hypermethioninemia is an excess of the amino acid methionine in the blood that can be asymptomatic or lead to intellectual disability, neurological problems, and liver dysfunction when severe.
Overview
Hypermethioninemia is an excess of the protein building block methionine in the blood. The condition arises when methionine is not broken down properly in the body.
Symptoms
- Often asymptomatic
- Intellectual disability
- Neurological problems
- Motor skill delays (standing, walking)
- Sluggishness
- Muscle weakness
- Liver problems
- Unusual facial features
- Breath, sweat, or urine smelling like boiled cabbage
Causes & Risk Factors
Primary Causes
Primary hypermethioninemia not associated with other metabolic disorders can result from variants in the following genes:
- MAT1A – encodes methionine adenosyltransferase, which converts methionine into S‑adenosylmethionine (AdoMet or SAMe)
- GNMT – encodes glycine N‑methyltransferase, which converts AdoMet to S‑adenosylhomocysteine (AdoHcy)
- AHCY – encodes S‑adenosylhomocysteine hydrolase, which converts AdoHcy to homocysteine
Deficiency of any of these enzymes leads to a buildup of methionine and related symptoms.
Secondary Causes
Hypermethioninemia can also occur with other metabolic disorders that impair molecule breakdown, such as:
- Homocystinuria
- Tyrosinemia
- Galactosemia
It may result from liver disease or excessive dietary intake of methionine, for example from large protein consumption or methionine‑enriched infant formula.
Inheritance
Hypermethioninemia can be inherited in different patterns:
- Autosomal recessive – both copies of the gene carry variants; parents are typically carriers without symptoms
- Autosomal dominant – one altered gene copy is sufficient to cause the disorder; an affected individual usually has one affected parent
Other Names
- Deficiency of methionine adenosyltransferase
- Glycine N‑methyltransferase deficiency (GNMT deficiency)
- Hepatic methionine adenosyltransferase deficiency (MAT deficiency)
- MET
- Methionine adenosyltransferase deficiency
- Methioninemia
- S‑adenosylhomocysteine hydrolase deficiency
Resources
Genetic Testing Information
- Hypermethioninemia with deficiency of S‑adenosylhomocysteine hydrolase
- Glycine N‑methyltransferase deficiency
- Hepatic methionine adenosyltransferase deficiency
Support and Advocacy
- National Organization for Rare Disorders (NORD)
Clinical Trials
- ClinicalTrials.gov
Gene and Disease Catalogs
- GLYCINE N‑METHYLTRANSFERASE DEFICIENCY
- HYPERMETHIONINEMIA WITH S‑ADENOSYLHOMOCYSTEINE HYDROLASE DEFICIENCY
- METHIONINE ADENOSYLTRANSFERASE I/III DEFICIENCY
Scientific Literature
- PubMed