glycine N-methyltransferase deficiency

Glycine N-methyltransferase (GNMT) deficiency is a rare genetic disorder that affects methionine metabolism in the body. It is characterized by persistent and isolated excess levels of methionine in the blood, known as hypermethioninemia.

Causes and Symptoms

The condition is caused by mutations or changes in the GNMT gene, which leads to impaired breakdown of methionine. The only clinical abnormalities associated with this disorder are mild increase of liver size (hepatomegaly) and chronic elevation of transaminase levels in the blood without liver damage.

Prevalence and Diagnosis

GNMT deficiency is a very rare condition, reported so far in only four patients. It can be diagnosed through molecular genetic studies that identify mutations in the GNMT gene.

Other Conditions with Similar Symptoms

It's worth noting that hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia, and galactosemia, which also involve faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine.

References

• [1] Glycine N-methyltransferase deficiency (GNMT deficiency) is a very rare condition characterized by persistent and isolated excess levels of methionine in the blood (hypermethioninemia). The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver damage. [2][3]
• [4] Glycine N-methyltransferase deficiency is caused by homozygous or compound heterozygous mutation in the GNMT gene on chromosome 6p21.
• [5] The reduced glycine N-methyltransferase activity resulting from GNMT gene variants impairs the breakdown of methionine, leading to hypermethioninemia. [6]
• [7] Hypermethioninemia can occur with other metabolic disorders, such as homocystinuria, tyrosinemia, and galactosemia, which also involve faulty breakdown of particular molecules. It can also result from liver disease or excessive dietary intake of methionine. [8][9]
• [10] Glycine N-methyltransferase deficiency is an inherited disorder of methionine metabolism, reported so far in only four patients and characterised by permanent hypermethioninemia. This disorder has been considered as probably benign because moderate hepatomegaly in two patients was the only obvious symptom and mild to moderate elevation of transaminases. [11]

Glycine N-methyltransferase (GNMT) deficiency is a rare genetic disorder that affects the metabolism of methionine, an essential amino acid. The signs and symptoms of this condition are relatively mild and may include:

• Mild hepatomegaly: A slight increase in liver size, which can be detected through physical examination or imaging tests [1][4][5].
• Elevated transaminase levels: Chronic elevation of liver enzymes in the blood without any significant liver damage [1][4][5].
• Upper respiratory tract infection: Some individuals with GNMT deficiency may experience recurrent upper respiratory tract infections, which can be a sign of impaired immune function [8][9].

In some cases, excess methionine due to GNMT deficiency can lead to more severe symptoms, including:

• Neurological problems: Excess methionine can cause neurological issues such as seizures or other signs and symptoms in some individuals with hypermethioninemia [6][10].
• Failure to thrive: Children with GNMT deficiency may experience failure to gain weight or grow at a normal rate due to impaired nutrient metabolism [8].

It's essential to note that the clinical presentation of GNMT deficiency can vary widely among affected individuals, and not everyone will exhibit all of these symptoms. A definitive diagnosis is typically made through genetic testing.

References: [1] The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver ... [4] The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver ... [5] The only clinical abnormalities are mild increase of the liver size (hepatomegaly) and chronic elevation of the transaminase levels in the blood without liver ... [6] Glycine N-methyltransferase deficiency is a rare genetic disorder characterized by hypermethioninemia, mild hepatomegaly, and elevated transaminase levels. The ... [8] What are the signs and symptoms? · Upper respiratory tract infection · Failure to thrive · Febrile convulsions. [9] Hypermethioninemia due to glycine N-methyltransferase deficiency is a rare, genetic inborn error of metabolism characterized by a relatively benign clinical ... [10] Aug 6, 2021 — Excess methionine can result in neurological problems and other signs and symptoms in some individuals with hypermethioninemia.

Diagnostic Tests for Glycine N-Methyltransferase Deficiency

Glycine N-methyltransferase (GNMT) deficiency is a rare genetic disorder that affects methionine metabolism. Diagnosing this condition requires a combination of clinical evaluation, laboratory tests, and molecular genetic testing.

• Clinical Evaluation: A full medical history, physical exam, and laboratory tests are essential to diagnose GNMT deficiency. Specialized blood and urine tests can be beneficial in identifying the condition.
• Molecular Genetic Testing: This is the most definitive test for diagnosing GNMT deficiency. It involves analyzing DNA samples from patients to identify mutations in the GNMT gene.

Specific Diagnostic Tests

1. Targeted Mutation Analysis: This test specifically looks for mutations in the GNMT gene, which can confirm a diagnosis of GNMT deficiency.
2. Mutation Scanning/Screning: This test is used to detect genetic mutations, including those that cause GNMT deficiency.
3. Genetic Testing: Genetic testing can identify mutations in the GNMT gene and confirm a diagnosis of GNMT deficiency.

Laboratory Tests

1. Blood Tests: Blood tests can help identify elevated levels of methionine and other related compounds in patients with GNMT deficiency.
2. Urine Tests: Urine tests can also detect abnormal levels of certain compounds, which can indicate GNMT deficiency.

Specialized Diagnostic Tests

1. Adenosine Kinase Deficiency Test: This test is used to diagnose adenosine kinase deficiency, a related condition that can present with similar symptoms.
2. Hypermethioninemia Test: This test measures the levels of methionine in the blood and can help identify GNMT deficiency.

References

• [1] Clinical resource with information about Glycine N-methyltransferase deficiency and its clinical features, GNMT, available genetic tests from US and labs around the world and links to practice guidelines and authoritative resources like GeneReviews, PubMed, MedlinePlus, clinicaltrials.gov, PharmGKB
• [2] Integrated disease information for Glycine N-Methyltransferase Deficiency including associated genes, mutations, phenotypes, pathways, drugs, and more - integrated from 75 data sources ... Genetic Tests for Glycine N-Methyltransferase Deficiency.
• [13] Glycine N-methyltransferase deficiency (GNMT) GTR Test ID Help Each Test is a specific, orderable test from a particular laboratory, and is assigned a unique GTR accession number.

Treatment Options for Glycine N-Methyltransferase Deficiency

Glycine N-methyltransferase (GNMT) deficiency is a rare genetic disorder that affects the body's ability to break down methionine, an essential amino acid. While there are no specific treatments available for GNMT deficiency, certain medications and dietary modifications may help manage the condition.

S-adenosylmethionine (SAMe) Treatment

One potential treatment option for GNMT deficiency is S-adenosylmethionine (SAMe), a compound that plays a crucial role in methionine metabolism. SAMe has been shown to be effective in treating hyperhomocysteinemia, a condition characterized by elevated levels of homocysteine in the blood, which can occur as a result of GNMT deficiency [4].

Low Methionine Diet

A low methionine diet may also be recommended for individuals with GNMT deficiency. This dietary approach involves reducing or eliminating foods that are high in methionine, such as meat, fish, and eggs, to help manage the condition [6].

Other Therapeutic Approaches

While there is limited research on specific drug treatments for GNMT deficiency, other therapeutic approaches may be considered on a case-by-case basis. These may include:

• Retinoic acid and glucocorticoid treatment, which have been shown to induce hepatic GNMT expression in animal models [10]
• Other medications that target related metabolic pathways, such as methionine adenosyltransferase I/III deficiency [9]

Consultation with a Healthcare Professional

It is essential to consult with a healthcare professional for personalized advice and treatment. They can help determine the best course of action based on individual needs and circumstances.

References:

[4] - Context 4: "S-adenosylmethionine treatment in methionine adenosyltransferase deficiency, a..."

[6] - Context 6: "...a low methionine diet may be used to correct the biochemical..."

[9] - Context 9: "...These are methionine adenosyltransferase I/III, glycine N-methyltransferase, S-adenosylhomocysteine hydrolase and adenosine kinase deficiencies."

[10] - Context 10: "Retinoic acid and glucocorticoid treatment induce hepatic glycine N-methyltransferase and lower plasma homocysteine concentrations in rats and..."

Glycine N-methyltransferase (GNMT) deficiency is a rare genetic disorder characterized by hypermethioninemia, mild hepatomegaly, and elevated transaminase levels [3]. To establish a differential diagnosis for GNMT deficiency, it's essential to consider other conditions that may present with similar symptoms.

Other Conditions with Similar Symptoms:

• Hyperhomocysteinemia: Elevated homocysteine levels can cause hypermethioninemia, which is similar to the condition seen in GNMT deficiency [9].
• Liver Diseases: Various liver diseases, such as hepatitis or cirrhosis, can lead to elevated transaminase levels and hepatomegaly, making them a differential diagnosis for GNMT deficiency [3].
• Metabolic Disorders: Certain metabolic disorders, like maple syrup urine disease, can also present with hypermethioninemia and elevated transaminase levels [1].

Key Differences:

• Genetic Cause: GNMT deficiency is caused by mutations in the GNMT gene, whereas other conditions may have different genetic or environmental causes.
• Clinical Presentation: While some conditions may share similar symptoms, such as hepatomegaly and elevated transaminases, the overall clinical presentation of GNMT deficiency can be distinct due to its specific genetic cause.

Diagnostic Approach:

To establish a differential diagnosis for GNMT deficiency, it's crucial to:

1. Genetic Testing: Perform genetic testing to identify mutations in the GNMT gene.
2. Biochemical Analysis: Conduct biochemical analysis to measure methionine and homocysteine levels.
3. Imaging Studies: Use imaging studies, such as ultrasound or CT scans, to assess liver size and function.

By considering these factors and performing the necessary diagnostic tests, healthcare providers can accurately diagnose GNMT deficiency and distinguish it from other conditions with similar symptoms.

References:

[1] Context result 6 [3] Context result 3 [9] Context result 9