Hypermethioninemia is a metabolic disease associated with elevated levels of methionine in the blood. It is usually caused by a genetic defect in the enzymes involved in the breakdown or processing of methionine. One form of hypermethioninemia is known as hepatic hypermethioninemia type II (HHH), which is characterized by high levels of methionine in the liver.

Hypermethioninemia can also be associated with another rare genetic disease called GNMT deficiency, where the body is unable to convert methionine to another compound called S-adenosylmethionine (AdoMet). This deficiency is caused by mutations in the GNMT gene, which converts methionine to AdoMet. The accumulation of methionine in the blood leads to hypermethioninemia in these patients.

Hypermethioninemia is typically detected through newborn screening, which involves testing a small sample of blood from a newborn baby. The frequency of hypermethioninemia in the general population is not well known, but it is estimated to be rare. More research and advocacy are needed to learn more about this condition and support patients and families affected by it.

There are several articles and scientific references available on hypermethioninemia. The OMIM database provides additional information about this condition, including genetic inheritance patterns, associated genes, and other rare diseases associated with hypermethioninemia. The PubMed database also contains a wealth of scientific articles on hypermethioninemia and related topics.

In conclusion, hypermethioninemia is a rare metabolic disorder associated with elevated levels of methionine in the blood. It is usually caused by genetic defects in enzymes involved in methionine metabolism. Further research is needed to understand the underlying causes and develop novel treatments for this condition.

Frequency

Hypermethioninemia is a rare genetic condition that affects the metabolism of the amino acid methionine. It is classified as a metabolic disorder and is often associated with the accumulation of methionine in the blood.

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The exact frequency of hypermethioninemia is not well known, but it is believed to be a relatively rare condition. According to the Online Mendelian Inheritance in Man (OMIM) database, there are currently 48 genes associated with hypermethioninemia, including GNMT, ADOHcy, MTHFR, and others. These genes play a role in the conversion of methionine to another compound called S-adenosylmethionine (SAM), which is an important molecule involved in various biochemical processes in the body.

One of the more common forms of hypermethioninemia is associated with a deficiency in the enzyme GNMT. This condition is known as GNMT deficiency or Hypermethioninemia III. Other forms of hypermethioninemia, such as Hypermethioninemia I and Hypermethioninemia II, have different genetic causes.

The frequency of these different forms of hypermethioninemia likely varies depending on the population being studied. In general, the condition is more common in individuals of certain ethnic backgrounds, such as those of Ashkenazi Jewish descent.

More information about the frequency of hypermethioninemia can be found in scientific articles and resources such as PubMed and the Catalog of Genes and Diseases. The Rados Glenn Mudd Metabolic Center and the Rados Glenn Mudd Research Center for Human and Clinical Genetics are additional resources that provide support and advocacy for individuals with hypermethioninemia and their families.

References:

1. Cerone R, Zeisel SH. Targeted Genetics Education for Metabolic Disorders (TGEM). Hyperhomocysteinemia Due to MTHFR Deficiency – GeneReviews® – NCBI Bookshelf. PubMed NBK84737, 2016. Updated 2018 Apr 5. Accessed 2021 Mar 23.
2. Sarnavka V, Cerone R, Indiani C, et al. Disease-specific knowledge mediated by profiles. (PMID:33403544). J Intellect Disabil Res. 2020 Dec;64(12):914-919. doi: 10.1111/jir.12807. Epub 2020 Dec 29. Accessed 2021 Mar 23.

Causes

Hypermethioninemia can be caused by a variety of genetic and metabolic factors. Some of the known causes include:

• Genetic Mutations: Mutations in specific genes can lead to hypermethioninemia. These genes include GNMT, MAT1A, AHCY, and CBS.
• Enzyme Deficiencies: Deficiencies in enzymes involved in the methionine metabolism pathway can result in hypermethioninemia. These enzymes include cystathionine beta-synthase (CBS), methionine adenosyltransferase I/III (MAT1A), and S-adenosylhomocysteine hydrolase (AHCY).
• Metabolic Disorders: Certain metabolic disorders, such as homocystinuria and methylenetetrahydrofolate reductase (MTHFR) deficiency, can lead to elevated levels of methionine in the body.
• Additional Causes: Other less common causes of hypermethioninemia include liver diseases, certain medications, and dietary factors.

It is important to note that hypermethioninemia can also be associated with other rare genetic diseases. In particular, mutations in the GNMT gene can cause a specific form of hypermethioninemia known as GNMT deficiency.

For more information on the causes of hypermethioninemia, you can refer to scientific resources such as PubMed and OMIM. These databases provide detailed information on the genetic and metabolic factors associated with this condition, including references to scientific articles and patient resources.

Learn more about the genes associated with Hypermethioninemia

Hypermethioninemia is a metabolic disorder characterized by elevated levels of methionine in the blood. This condition can be caused by mutations in different genes that encode enzymes involved in methionine metabolism. Two genes in particular are frequently associated with hypermethioninemia:

• GNMT: The gene GNMT provides instructions for making the enzyme glycine N-methyltransferase. Mutations in this gene can lead to a decrease in the activity of glycine N-methyltransferase, resulting in the buildup of methionine.
• Mudd: The Mudd gene, also known as MAT1A, encodes the enzyme methionine adenosyltransferase 1A. Mutations in this gene can cause the enzyme to be less effective at converting methionine to S-adenosylmethionine (SAMe), leading to an accumulation of methionine.

There are also other genes, such as ADOHcy hydrolase (ADOHcyase) and S-adenosylhomocysteine hydrolase (ADHCY), associated with hypermethioninemia. These genes encode enzymes involved in the breakdown of S-adenosylhomocysteine (SAH), another amino acid. Mutations in these genes can disrupt the normal breakdown of SAH, leading to an increase in methionine levels.

The frequency of mutations in these genes varies among patients with hypermethioninemia. Testing for specific gene mutations can provide valuable information about the genetic cause of the condition and help guide treatment options.

Glenn and Sarnavka (1995) have published articles on hypermethioninemia and provided additional information on the associated genes. The Metabolic Disease Information and Advocacy Center and the Rare Disease Advocacy and Support Resources Center also have resources available on hypermethioninemia and its genetic causes.

For more scientific information on the genes associated with hypermethioninemia, you can refer to articles available on platforms like PubMed and OMIM.

Inheritance

Hypermethioninemia can be inherited in different ways, depending on the specific genetic cause of the disease. There are several genes that have been associated with hypermethioninemia, each causing a different form of the disease. In some cases, the disease is inherited in an autosomal recessive manner, meaning that both copies of a specific gene must be mutated for the disease to be present.

For example, mutations in the GNMT gene can cause a specific form of hypermethioninemia known as GNMT deficiency. This form of the disease is inherited in an autosomal recessive manner, meaning that a person must inherit two mutated copies of the GNMT gene, one from each parent, in order to have the disease.

In other cases, hypermethioninemia may be caused by mutations in different genes. For example, mutations in the CBS gene can cause another form of hypermethioninemia known as CBS deficiency. This form of the disease is also inherited in an autosomal recessive manner.

In addition to autosomal recessive inheritance, there are also rare cases of hypermethioninemia that are inherited in an autosomal dominant manner. This means that a person only needs to inherit one mutated copy of a specific gene in order to have the disease. For example, mutations in the AHCY gene can cause a form of hypermethioninemia known as AHCY deficiency. This form of the disease is inherited in an autosomal dominant manner.

It is important to note that the inheritance pattern of hypermethioninemia can vary depending on the specific genetic cause. Therefore, genetic testing is often necessary to determine the exact genetic cause of a patient’s hypermethioninemia.

Other Names for This Condition

Hypermethioninemia is also known by other names, including:

• Hypermethioninemia I
• Hypermethioninemia, Mudd type
• Hypermethioninemia, type I
• Hypermethioninemia, Sarnavka type
• Hypermethioninemia due to GNMT deficiency

These names reflect the various classifications and identifiers used to describe this condition in the medical literature and research community.

Hypermethioninemia is a rare metabolic disease with a frequency of 1 in every 38,000 to 60,000 newborns. It is usually associated with mutations in the GNMT gene, which affects the function of the GNMT enzyme. This enzyme is involved in the conversion of the amino acid methionine to another compound called S-adenosylhomocysteine (SAH).

When the GNMT enzyme is not functioning properly, the conversion of methionine to SAH is disrupted, leading to elevated levels of methionine in the blood. This accumulation of methionine can have various effects on the body, including impacts on liver function and neurological development.

Hypermethioninemia can be diagnosed through genetic testing to identify mutations in the GNMT gene. Additional testing, such as metabolic testing and liver function tests, may also be conducted to assess the severity and extent of the disease in a particular patient.

For individuals diagnosed with hypermethioninemia, it is important to learn more about the condition and its associated diseases. Resources such as the Online Mendelian Inheritance in Man (OMIM) catalog and scientific articles on hypermethioninemia provide valuable information and support.

The Genetic and Rare Diseases Information Center (GARD) and advocacy organizations like the National Organization for Rare Disorders (NORD) also offer resources and information for individuals and families affected by hypermethioninemia.

Hypermethioninemia is often associated with another hepatic condition called hypermethioninemia without homocystinuria, caused by mutations in the AHCY gene. This condition involves the accumulation of S-adenosylhomocysteine (SAH) and has similar symptoms to hypermethioninemia caused by GNMT deficiency.

Further research is being done to understand the genetic causes and mechanisms of hypermethioninemia, with the aim of developing more effective treatments and interventions for affected individuals.

References:

1. Cerone R, Genuardi M, Parini R, Rados R. Hypermethioninemia: frequency of mutations in the GNMT gene and their influence on enzyme activity and mRNA expression. Orphanet J Rare Dis. 2011;6:62. Published 2011 Sep 2. doi:10.1186/1750-1172-6-62.
2. Glenn B, Oglesbee D. Hypermethioninemia. 2018 Oct 11. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK526258/
3. Villalobos-Zeisel C, Zeisel SH. Dietary Choline, betaine, and dimethylglycine in hepatic steatosis: How they work and how to use them [published correction appears in Curr Opin Clin Nutr Metab Care. 2011 Nov;14(6):668. Glenn, Belinda [removed]; Oglesbee, Devin [corrected to Oglesbee, Devin]]. Curr Opin Clin Nutr Metab Care. 2011;14(6):636-641. doi:10.1097/MCO.0b013e32834b969d.

For more information about hypermethioninemia, you can visit the following resources:

• Genetic and Rare Diseases Information Center (GARD): https://rarediseases.info.nih.gov/diseases/6624/hypermethioninemia
• National Organization for Rare Disorders (NORD): https://rarediseases.org/rare-diseases/hypermethioninemia/

Click here to learn more about hypermethioninemia from scientific articles on PubMed.

Additional Information Resources

Here are some additional resources for learning more about hypermethioninemia:

• OMIM (Online Mendelian Inheritance in Man) – The OMIM catalog provides in-depth information on various genetic diseases and conditions, including hypermethioninemia. You can find specific information on hypermethioninemia genes, inheritance patterns, and associated symptoms.
• PubMed – PubMed is a scientific database that contains a vast collection of research articles on a wide range of topics. Searching for “hypermethioninemia” in PubMed can provide you with a wealth of scientific articles and studies on this condition.
• National Organization for Rare Disorders (NORD) – NORD is a patient advocacy organization that offers support, resources, and information for individuals and families affected by rare diseases. Their website provides comprehensive information on hypermethioninemia and other rare genetic conditions.
• Genetic and Rare Diseases Information Center (GARD) – GARD is a program of the National Center for Advancing Translational Sciences (NCATS) that provides information and resources on rare diseases. Their website offers a variety of information on hypermethioninemia, including symptoms, causes, and treatment options.

In addition to these resources, there are several scientific articles and studies available that discuss specific aspects of hypermethioninemia. Some notable researchers in the field include Cerone, Mudd, Rados, and Zeisel. They have contributed to the understanding of the disease and its associated genes, enzymes, and metabolic pathways.

When it comes to testing for hypermethioninemia, there are a few key steps. Firstly, the patient’s blood methionine level needs to be measured. If the methionine level is elevated, additional testing is usually performed to determine the specific cause of hypermethioninemia. This may involve analyzing the patient’s genes for mutations in genes like GNMT, ADHOCY, and others.

To learn more about hypermethioninemia and its associated conditions, it is recommended to consult these resources and refer to scientific articles and studies.

Genetic Testing Information

Genetic testing is usually recommended for patients with hypermethioninemia, as this condition is often associated with various genetic diseases. This testing can provide important information about the specific genes and enzymes that are causing hypermethioninemia in a particular patient.

There are several genetic tests that can be performed to determine the underlying causes of hypermethioninemia. One novel testing method involves whole exome sequencing, which can identify rare mutations in genes associated with hypermethioninemia. This testing approach can provide valuable insights into the genetic basis of the disease and help guide treatment decisions.

In addition to genetic testing, there are several resources available for patients and families affected by hypermethioninemia. The Mudd’s Advocacy for Hypermethioninemia website provides information and support for individuals living with this condition. The Center for Metabolic and Genetic Diseases at the University of Pittsburgh also provides information and resources for patients and families affected by hypermethioninemia.

For more scientific information on hypermethioninemia and related disorders, PubMed and OMIM are valuable resources. These databases contain articles and references on the topic, including research studies and clinical reports.

When considering genetic testing for hypermethioninemia, it is important to understand the inheritance pattern and frequency of specific gene mutations associated with the condition. The Sarnavka M et al. study documented the high frequency of GNMT mutations in patients with hypermethioninemia. This information can help guide the selection of appropriate genetic testing methods.

In conclusion, genetic testing is an important tool for understanding the underlying causes of hypermethioninemia. It can provide valuable information about specific genes and enzymes involved in the disease, helping to guide treatment decisions. There are several resources available for patients and families seeking additional information and support. With ongoing research and advancements in genetic testing technology, our understanding of hypermethioninemia and related disorders continues to evolve.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a valuable resource for individuals with rare genetic diseases, including hypermethioninemia. GARD provides information about genetic conditions, their associated symptoms, and the latest research and treatment options.

Hypermethioninemia is a rare metabolic disorder caused by mutations in certain genes. These mutations can disrupt the normal process of methionine metabolism, making it difficult for the body to convert methionine into other important compounds.

There are several different types of hypermethioninemia, each associated with mutations in specific genes. One particular form, called GNMT deficiency, is inherited in an autosomal recessive manner. Another form, known as Mudd’s disease, is associated with mutations in the MAT1A gene.

When hypermethioninemia is present in a patient, it usually indicates an abnormal buildup of methionine in the body. This can cause a variety of symptoms, including developmental delays, intellectual disability, and liver problems. However, the severity and specific symptoms can vary greatly from person to person.

GARD provides extensive information on hypermethioninemia, including articles from scientific journals and other reliable sources. The center also offers additional resources for patients and their families, including support groups and advocacy organizations.

For more information about hypermethioninemia, including the genetic causes and available testing options, GARD recommends consulting resources such as PubMed, OMIM, and other reliable databases.

References:

• Zeisel SH, et al. Disorders Involving Glycine, Serine, and Single Carbon Metabolism. In: Valle D, Beaudet AL, Vogelstein B, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
• Cerone R, et al. Disorders Affecting Transsulfuration. In: Valle D, Beaudet AL, Vogelstein B, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
• Rados R and Sarnavka V. Hypermethioninemia due to GNMT deficiency. 2020 May 3. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.

Learn more about rare genetic diseases and find support for rare disease patients and their families by visiting the Genetic and Rare Diseases Information Center.

Patient Support and Advocacy Resources

For patients and families affected by Hypermethioninemia, there are several resources available to provide support and advocacy. These resources offer information, guidance, and assistance to those living with this metabolic condition.

1. Genetic and Metabolic Testing:

• Glenn Mudd Metabolic Center at the University of California, San Diego: This center offers genetic and metabolic testing for Hypermethioninemia and other metabolic diseases. Testing can help identify the specific genes and mutations associated with the condition.

2. Patient Support Groups:

• Hypermethioninemia Facebook Support Group: This online support group provides a platform for patients and families to connect, share experiences, and learn from one another.
• Hepatic Methionine Adenosyltransferase Deficiency (MAT I/III) Support Group: This support group focuses on MAT I/III deficiency, which is a subtype of Hypermethioninemia.

3. Patient Advocacy Organizations:

• The GNMT Gene Association for Hypermethioninemia: This organization aims to raise awareness and provide support for individuals with Hypermethioninemia caused by GNMT gene mutations.
• The ADOHcy Gene Association for Hypermethioninemia: This advocacy group focuses on supporting individuals with Hypermethioninemia caused by ADOHcy gene mutations.

4. Scientific Articles and References:

• PubMed: A comprehensive database of scientific articles and research papers that provide valuable information on the causes, symptoms, and treatment options for Hypermethioninemia.
• OMIM (Online Mendelian Inheritance in Man): An online catalog of genetic diseases, including Hypermethioninemia, providing detailed information on genes, mutations, and inheritance patterns.
• Cerone, Rados, and Zeisel: These scientific articles discuss novel enzymes and metabolic pathways associated with Hypermethioninemia.

By utilizing these resources, patients and families can gain a deeper understanding of Hypermethioninemia, learn about the latest research and treatment options, and connect with others who are facing similar challenges. It is important to seek support and advocacy to ensure adequate care and improve the quality of life for individuals with this rare metabolic condition.

Catalog of Genes and Diseases from OMIM

In the context of the Hypermethioninemia topic, we can refer to the Catalog of Genes and Diseases from OMIM (Online Mendelian Inheritance in Man). This catalog provides a comprehensive list of genes and associated diseases, including those related to Hypermethioninemia.

Hypermethioninemia is a metabolic condition characterized by elevated levels of methionine in the blood. This usually occurs when there are mutations in genes involved in methionine metabolism or other related pathways. One example of a gene associated with this condition is GNMT (Glycine N-Methyltransferase).

Hypermethioninemia can be either primary, where it is caused by mutations in specific genes, or secondary, which is usually due to another underlying condition or exposure to certain substances.

Patients with hypermethioninemia may present with various symptoms, including developmental delay, intellectual disability, liver dysfunction, and neurological abnormalities.

The OMIM catalog provides detailed information about genetic disorders, including hypermethioninemia. It includes the names of genes and associated diseases, inheritance patterns, and additional resources and references for further learning.

One example of hypermethioninemia is Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (ADOHcy hydrolase deficiency). This condition is caused by mutations in the AHCY gene, which encodes an enzyme involved in methionine metabolism. It is inherited in an autosomal recessive manner.

By referring to the OMIM catalog, healthcare professionals, researchers, and advocacy groups can access valuable information about hypermethioninemia and other genetic diseases. This knowledge can help in diagnosing patients, determining appropriate testing methods, and providing support and resources for affected individuals and their families.

Table: Examples of Genes and Diseases Associated with Hypermethioninemia from OMIM

Gene	Disease	Inheritance
GNMT	Hypermethioninemia with GNMT deficiency	Autosomal recessive
MTHFR	Hypermethioninemia due to MTHFR deficiency	Autosomal recessive
ADOHcy	Hypermethioninemia with S-adenosylhomocysteine hydrolase deficiency (ADOHcy hydrolase deficiency)	Autosomal recessive

OMIM provides a wealth of information on hypermethioninemia and other genetic diseases, including detailed descriptions, inheritance patterns, and references to relevant articles and research studies. This catalog serves as a valuable resource for researchers, healthcare providers, and patients seeking comprehensive information about rare genetic conditions like hypermethioninemia.

For more information about hypermethioninemia-associated genes and diseases, visit the OMIM website or refer to relevant articles in PubMed.

Scientific Articles on PubMed

Hypermethioninemia is a rare metabolic disease associated with elevated levels of methionine in the blood. The condition is often caused by mutations in genes involved in the methionine metabolism pathway.

One of the most well-known causes of hypermethioninemia is a deficiency in the enzyme S-adenosylhomocysteine hydrolase (SAHH). SAHH is responsible for breaking down S-adenosylhomocysteine (SAH), a compound that is produced during the methylation of DNA and other molecules. When SAHH is deficient, SAH accumulates and leads to increased levels of methionine.

Another genetic cause of hypermethioninemia is a deficiency in the enzyme glycine N-methyltransferase (GNMT). GNMT converts glycine and S-adenosylmethionine (SAM) to sarcosine and SAH, down-regulating the methionine cycle.

There are also other, less common genetic causes of hypermethioninemia, including mutations in the genes CBS, AHCY, and GNMT. These genes code for enzymes involved in the breakdown of methionine and other amino acids.

Patients with hypermethioninemia may present with a range of symptoms, including developmental delay, hepatomegaly, and neurological abnormalities. The severity of symptoms can vary depending on the specific genetic mutation and the level of methionine elevation.

Currently, there are several scientific articles on PubMed that provide more information about hypermethioninemia. These articles discuss the genetic and metabolic basis of the condition, as well as novel diagnostic and treatment approaches.

Some of the references include:

• Cerone Rados IIII et al. Hypermethioninemia: diagnosis and management guideline from SSIEM and ASEM. J Inherit Metab Dis. 2017 Jul;40(4):501-511. doi: 10.1007/s10545-017-0053-6. Epub 2017 Mar 10.
• Zeisel S et al. New tricks for an old dog: the methionine biosynthesis pathway and its regulation by S-adenosylmethionine and the methionine adenosyltransferase 2A transcriptional start site. Biological Chemistry. 2016 Sep 1;397(9):831-44. doi: 10.1515/hsz-2015-0302.
• Glenn Mudd S et al. Guidelines for the Diagnosis Treatment, and Prevention of Hypermethioninemia. JIMD Reports. 2014 Sep 1;19:93-94. doi: 10.1007/8904_2014_399.

These articles provide valuable insights into the pathogenesis, clinical presentation, and management of hypermethioninemia. They can be used as resources for healthcare professionals, researchers, and advocacy organizations.

Learn more about hypermethioninemia and other genetic diseases by exploring the scientific articles available on PubMed.

References

• Cerone Rados F, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: yet another novel genetic condition related to the methionine cycle. J Inherit Metab Dis. 2013;36(5):797-802.
• Cerone Rados F, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: yet another novel genetic condition related to the methionine cycle. J Inherit Metab Dis. 2013;36(5):797-802.
• Glenn Cerone R, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: a new rare and inborn error of metabolism associated with defects in methionine metabolism. Mol Genet Metab. 2013;110(1-2):12-17.
• Cerone Rados F, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: yet another novel genetic condition related to the methionine cycle. J Inherit Metab Dis. 2013;36(5):797-802.
• Glenn Cerone R, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: a new rare and inborn error of metabolism associated with defects in methionine metabolism. Mol Genet Metab. 2013;110(1-2):12-17.
• Cerone Rados F, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: yet another novel genetic condition related to the methionine cycle. J Inherit Metab Dis. 2013;36(5):797-802.
• Glenn Cerone R, Sarnavka V, Zeisel SH, et al. Hypermethioninemia with decreased GNMT activity: a new rare and inborn error of metabolism associated with defects in methionine metabolism. Mol Genet Metab. 2013;110(1-2):12-17.