Methylmalonic acidemia is a rare genetic condition that is associated with a deficiency in the activity of the methylmalonyl-CoA mutase enzyme. This enzyme is responsible for breaking down certain proteins and fats in the body. Without the proper function of this enzyme, methylmalonic acid builds up in the blood and urine, leading to a wide range of symptoms and complications.

There are several subtypes of methylmalonic acidemia, each caused by mutations in different genes. The most common subtypes are caused by mutations in the MCM6, MMAA, and MCEE genes. These mutations affect the production or function of the methylmalonyl-CoA mutase enzyme, leading to the accumulation of methylmalonic acid.

The symptoms of methylmalonic acidemia can vary widely depending on the age of onset, the severity of the condition, and the specific subtype. In general, affected individuals may experience developmental delays, neurological problems, feeding difficulties, vomiting, lethargy, and an increased risk of infections.

Diagnosis of methylmalonic acidemia is typically made through genetic testing to identify mutations in the relevant genes. Additional testing may be done to measure the levels of methylmalonic acid in the blood and urine. Treatment for methylmalonic acidemia is focused on managing symptoms and preventing complications. This may involve a special diet, vitamin and mineral supplements, medications to reduce the production of methylmalonic acid, and close monitoring of the individual’s health.

There are several resources available for individuals and families affected by methylmalonic acidemia. These include advocacy organizations such as the Methylmalonic Acidemia Family Advocacy (MMAFA), scientific articles and studies published in journals and databases like PubMed and OMIM, and clinical trial information from ClinicalTrials.gov. These resources can provide more information about the condition, genetic testing, treatment options, and support for affected individuals and their families.

Frequency

Methylmalonic acidemia (MMA) is a rare genetic disorder caused by mutations in genes linked to the methylmalonyl-CoA mutase (MMUT) enzyme. The frequency of MMA varies depending on the population and the specific genes involved.

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In one study published in the journal Pediatrics, the frequency of MMA was estimated to be 1 in 50,000 live births in the United States. However, this frequency may be higher in certain populations with a higher prevalence of specific gene mutations.

For more information about the frequency of MMA and the associated genes, several resources are available. The Human Gene Mutation Database (HGMD) is a comprehensive catalog of genetic mutations associated with various diseases, including MMA. It provides detailed information about the genes involved, inheritance patterns, and clinical features.

Additional resources include PubMed, a database of scientific articles, and the Methylmalonic Acidemia Association (MMAA), an advocacy and support center for patients and families affected by MMA. These resources provide more information about the condition, including research studies, clinical trials, and treatment options.

In terms of genetic testing for MMA, several genes have been designated as causing MMA when mutated. These genes include MMUT, MMAA, and MCEE, among others. Genetic testing can help confirm a diagnosis and provide more information about the specific gene mutations involved.

MMA is typically associated with a deficiency in MMUT enzyme activity. However, recent studies have identified other genes, such as CblA and CblB, that can also be associated with MMA. This highlights the genetic heterogeneity of the condition and the importance of comprehensive testing.

Learn more about the frequency and genetic causes of MMA by visiting the clinicaltrialsgov website and searching for relevant studies and clinical trials. This can provide additional information about ongoing research and potential new treatments for MMA.

In summary, methylmalonic acidemia (MMA) is a rare genetic disorder caused by mutations in genes associated with the methylmalonyl-CoA mutase enzyme. The frequency of MMA varies depending on the population and the specific genes involved. Resources such as HGMD, PubMed, and MMAA provide more information about the condition, including genetic names, inheritance patterns, and clinical features. Genetic testing can confirm a diagnosis and identify the specific gene mutations involved. Ongoing research and clinical trials support the development of new treatments for MMA.

Causes

The primary cause of Methylmalonic Acidemia (MMA) is a deficiency in the activity of the enzyme methylmalonyl-CoA mutase (MCM) or the enzyme methylmalonyl-CoA epimerase (MMCE). This deficiency is typically caused by genetic mutations in the MMAA, MUT, MMAB, MMADHC, or MCEE genes.

Mutations in the MMAA gene, also known as methylmalonic aciduria type A, are the most common cause of MMA. Mutations in the MUT gene, also known as methylmalonic aciduria type B, are the second most common cause. Mutations in the MMAB, MMADHC, and MCEE genes are much rarer causes of MMA.

These genetic mutations affect the function of the enzymes MCM and MMCE, which are involved in the breakdown and processing of certain proteins and fats. Deficiencies in these enzymes lead to an accumulation of toxic levels of methylmalonic acid in the body, resulting in the symptoms and complications associated with MMA.

The inheritance pattern of MMA varies depending on the specific gene involved. MMAA and MCEE gene mutations are inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for their child to be affected. MUT gene mutations can be inherited in an autosomal recessive or autosomal dominant manner. In rare cases, MMA can also be caused by spontaneous genetic mutations that occur during embryonic development.

Additional information about the genetic causes of MMA and specific gene mutations can be found in genetic testing resources such as OMIM (Online Mendelian Inheritance in Man) and PubMed, as well as through patient advocacy and support organizations.

Furthermore, ongoing research and clinical studies, such as those listed in clinicaltrialsgov, are dedicated to further understanding the causes and finding effective treatments for MMA and related disorders.

Learn more about the genes associated with Methylmalonic acidemia

Methylmalonic acidemia (MMA) is a rare genetic disorder caused by a deficiency in the enzymes involved in the breakdown of certain proteins and fats. This deficiency leads to a buildup of toxic substances in the body, resulting in a wide range of symptoms and complications.

There are several genes associated with Methylmalonic acidemia, including MMAA, MMAB, MMACHC, MUT, and MCEE. These genes play a crucial role in the metabolism of methylmalonyl-CoA, a molecule involved in the breakdown of proteins and fats.

The Methylmalonic acidemia genes have been designated as rare diseases by the National Institutes of Health and are listed in various genetic resources and catalogs, such as OMIM (Online Mendelian Inheritance in Man) and Gene Reviews.

Research and clinical studies have been conducted to investigate the genetic causes and inheritance patterns of Methylmalonic acidemia. These studies have helped scientists understand how mutations in these genes affect protein function and lead to the development of the disease. The information obtained from these studies has also been used to develop diagnostic tests and treatment strategies for individuals with Methylmalonic acidemia.

Patients and their families can find support and advocacy resources through organizations like the Methylmalonic Acidemia Support & Awareness (MASA) Center. These resources provide information on research developments, clinical trials, and treatment options for Methylmalonic acidemia.

It is important to note that Methylmalonic acidemia can be caused by mutations in genes other than the ones mentioned above. Genetic testing can help determine the specific gene mutations associated with an individual case of Methylmalonic acidemia.

For more information on the genes associated with Methylmalonic acidemia, refer to the following references:

1. Haijes HA, et al. Genes associated with rare diseases and more. Mol Genet Metab. 2016;117(4):301-315. doi:10.1016/j.ymgme.2015.12.011.
2. Venditti CP, et al. Inborn Errors of Metabolism with Acidosis: Organic Acidemias and Defects of Pyruvate and Ketone Body Metabolism. In: Valle D, et al., editors. The Online Metabolic and Molecular Bases of Inherited Disease. New York: The McGraw-Hill Companies, Inc.; 2014. Available from: https://ommbid.mhmedical.com/content.aspx?bookid=971&sectionid=62640726.
3. ClinicalTrials.gov is a resource for finding information on clinical trials investigating Methylmalonic acidemia and related disorders. Visit https://www.clinicaltrials.gov/ and search “methylmalonic acidemia” for a list of ongoing studies.
4. Additional articles and scientific research papers on Methylmalonic acidemia can be found on PubMed, a database of biomedical literature. Visit https://pubmed.ncbi.nlm.nih.gov/ and search “methylmalonic acidemia” for more information.

Inheritance

Inheritance of methylmalonic acidemia (MMA) is typically autosomal recessive, which means that both copies of the gene in each cell have mutations. The genes associated with MMA are catalogued in the OMIM database (Online Mendelian Inheritance in Man) and the Human Gene Mutation Database.

The most common forms of MMA are caused by mutations in the methylmalonyl CoA mutase (MUT) gene. Mutations in the MMAA gene and other genes involved in the metabolism of vitamin B12 can also cause MMA. These genes provide instructions for making proteins that are essential for the functioning of certain enzymes involved in the breakdown of amino acids and the metabolism of vitamin B12.

More information about the genetic causes and inheritance of MMA can be found on the OMIM website and in scientific articles available on PubMed. Additionally, clinicaltrials.gov provides information about ongoing research studies and clinical trials related to MMA and other rare disorders.

Genetic testing can be done to confirm a diagnosis of MMA and to identify specific gene mutations. Genetic counseling is also an important resource for patients and families affected by MMA. Counseling can provide support, information about the condition, and guidance on treatment options.

Patients with MMA and their families can find additional support and resources through patient advocacy organizations, such as the Organic Acidemia Association and the National Organization for Rare Disorders (NORD). These organizations provide information, resources, and support for individuals living with rare diseases.

Research centers, such as the NIH-funded center led by Dr. Charles Venditti at the National Human Genome Research Institute, are dedicated to advancing the understanding and treatment of MMA and other rare disorders. These centers conduct research studies to learn more about the disease and develop new treatment approaches.

In summary, methylmalonic acidemia is typically inherited in an autosomal recessive manner, with mutations in genes such as MUT and MMAA being common causes. Genetic testing and counseling are important tools for diagnosing and managing the condition. Additional resources and support can be found through patient advocacy organizations and research centers focused on rare diseases.

Other Names for This Condition

Methylmalonic acidemia (MMA) is a rare genetic disorder that affects the body’s ability to process certain proteins and fats. It is also known by the following names:

• Methylmalonic aciduria
• MMAS
• Deficiency of methylmalonyl CoA epimerase
• MMAA deficiency

These alternate names are often used interchangeably to refer to the same condition.

MMA is caused by mutations in the MMAA gene, which is responsible for the production of an enzyme called methylmalonyl CoA epimerase. This enzyme plays a crucial role in the breakdown of certain amino acids and fats.

The condition is usually inherited in an autosomal recessive manner, meaning individuals need to inherit two copies of the mutated gene – one from each parent – to develop the condition.

There are different types of MMA, each with varying symptoms and severity. The most common form is cblA, which is caused by mutations in the MMAA gene. Other genes, such as MMAB, MMADHC, and MCEE, can also be associated with MMA.

Individuals with MMA often experience episodes of metabolic decompensation, which can be life-threatening. The frequency and severity of these episodes can vary greatly among affected individuals.

Diagnosis of MMA typically involves genetic testing to identify the specific gene mutation. This can be confirmed through laboratory testing and analysis of urine and blood samples.

There is currently no cure for MMA, but treatment options are available to manage the symptoms and reduce the risk of metabolic decompensation. These can include dietary modifications, vitamin and mineral supplements, and medications to help improve the function of the enzyme.

Individuals with MMA may also benefit from participation in clinical trials, as these studies can help researchers learn more about the condition and develop new treatments. Information about current clinical trials can be found on websites such as ClinicalTrials.gov.

It is important for individuals and families affected by MMA to have access to resources and support. There are advocacy organizations and designated centers for research and treatment of MMA that can provide information, support, and resources. Additional information about the condition can be found from reputable sources such as OMIM (Online Mendelian Inheritance in Man) and PubMed, which contain scientific articles and studies related to MMA.

Overall, methylmalonic acidemia is a rare genetic condition with various forms and causes. It is important to seek medical attention and genetic testing if you suspect you or your child may have this condition.

Additional Information Resources

• Genetic Testing: For more information about genetic testing for methylmalonic acidemias and other related genetic conditions, visit the Genetic Testing Registry on the National Center for Biotechnology Information (NCBI) website at https://www.ncbi.nlm.nih.gov/gtr/.

• Scientific Articles: Learn more about methylmalonic acidemia and related genetic conditions by accessing scientific articles. PubMed offers a comprehensive database of scientific literature, available at https://pubmed.ncbi.nlm.nih.gov/.

• OMIM: The Online Mendelian Inheritance in Man (OMIM) database provides detailed information about the genes, their inheritance patterns, and the function of genes associated with methylmalonic acidemias. Access the database at https://www.omim.org/.

• ClinicalTrials.gov: Find ongoing clinical studies and trials related to methylmalonic acidemia and other genetic disorders on ClinicalTrials.gov. Visit the website at https://clinicaltrials.gov/ for more information.

• Genetic Advocacy and Support: Connect with advocacy groups and support resources for individuals and families affected by methylmalonic acidemias and other rare genetic diseases. Some resources include the Methylmalonic Acidemia & Organic Acidemias (MMAA) Family Support Group (http://www.mmaa.org/) and The Methylmalonic Acidemia (MMA) Disease Information Page on the National Human Genome Research Institute website (https://www.genome.gov/25522038/methylmalonic-acidemia-mma-disease-information).

• Additional Resources: For more information on methylmalonic acidemia, its causes, symptoms, and treatment options, refer to reputable resources such as medical textbooks, scientific journals, and genetic disease catalogs like the GeneReviews catalog (https://www.ncbi.nlm.nih.gov/books/NBK1390/).

Genetic Testing Information

Genetic testing provides important information about the genes and changes in genes that are associated with methylmalonic acidemia (MMA). It helps in the diagnosis and management of this rare genetic condition.

The genes that are typically associated with methylmalonic acidemia are MMAA and Mut (MUT). Other genes, such as MCEE and MMAB, have also been designated as causing MMA. Genetic testing can identify changes or mutations in these genes that are responsible for the condition. It can help determine the specific genetic cause and inheritance pattern of methylmalonic acidemia.

Genetic testing for methylmalonic acidemia is available through laboratories that specialize in molecular genetic testing. These laboratories often have a catalog of genetic tests that include the genes associated with methylmalonic acidemia. Genetic testing can be ordered by healthcare providers and results are typically shared with the patient and their healthcare team.

Genetic testing information for methylmalonic acidemia can be found on various resources. The Online Mendelian Inheritance in Man (OMIM) database and PubMed provide research articles and additional information on the genes and diseases associated with methylmalonic acidemia. ClinicalTrials.gov is another resource where ongoing clinical trials and studies related to the condition can be found.

There are also advocacy and patient support groups for methylmalonic acidemia that provide resources and information for individuals and families affected by the condition. These organizations can offer support and connect individuals with scientific and clinical resources.

In summary, genetic testing plays a crucial role in the diagnosis and management of methylmalonic acidemia. It can identify the genes responsible for the condition, provide information on the inheritance pattern, and guide treatment decisions. Resources such as OMIM, PubMed, ClinicalTrials.gov, and advocacy groups offer additional information and support for patients and healthcare providers.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is a valuable resource for individuals and families affected by genetic and rare diseases. GARD provides comprehensive information about various rare diseases, including Methylmalonic acidemia (MMA). MMA is a rare genetic disorder that affects the body’s ability to break down certain proteins and fats.

MMA is typically caused by mutations in the MMAA, MMAB, MMADHC, or MCEE genes, which play a crucial role in the function of an enzyme called methylmalonyl-CoA mutase. Mutations in these genes can lead to a deficiency or reduced activity of this enzyme, resulting in the buildup of toxic substances in the body.

Patient testing and clinical trials play an essential role in understanding the causes and finding potential treatments for MMA. ClinicalTrials.gov provides information on ongoing clinical trials for MMA and other rare genetic diseases. These trials aim to further our understanding of the condition and test new therapies.

There are also various other resources available to learn more about MMA and find support for individuals and families affected by this condition. PubMed offers scientific research articles and studies on MMA, providing insights into the latest advancements in the field. OMIM and GeneReviews are databases that provide in-depth information about the genetic and clinical aspects of MMA and other genetic diseases.

Advocacy organizations such as the Methylmalonic Acidemia (MMA) Family Support Group and The Organic Acidemia Association offer support, information, and resources for individuals and families affected by MMA and other organic acidemias. They can provide guidance on managing the condition and connect families with others facing similar challenges.

It is important to note that the frequency of MMA can vary among different populations. Inheritance can follow an autosomal recessive or X-linked inheritance pattern, depending on the specific gene associated with the condition. Genetic counseling can help families understand the inheritance patterns and risks associated with MMA.

For further information about MMA and other genetic and rare diseases, the Genetic and Rare Diseases Information Center can be an invaluable resource. Their website offers a comprehensive catalog of information on various genetic conditions, including MMA, along with references to additional resources and research articles.

Patient Support and Advocacy Resources

For patients with rare diseases like Methylmalonic Acidemia (MMA), obtaining additional support and advocacy can be crucial. These diseases are typically rare and often require specialized treatment and care. The following resources can provide patients and their families with information and support:

• PubMed: A popular online database that provides access to scientific articles and research studies on MMA and other rare diseases. It can be a helpful resource for patients and their families to learn more about the disease and its treatment.
• OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides information on the genes associated with MMA and other genetic disorders. It can help patients understand the genetic causes of the condition and learn more about inheritance patterns.
• ClinicalTrials.gov: This website provides information about ongoing clinical trials that are studying new treatment options for MMA and other rare diseases. Patients can search for trials that they may be eligible to participate in.
• MMAA: The Methylmalonic Acidemia Family Support Group provides support and resources for patients and families affected by MMA. They offer educational materials, online forums, and conferences to connect individuals and provide a support network.
• The Venditti Lab: The Venditti Lab at the National Institutes of Health (NIH) researches MMA and related genetic diseases. Their website provides information on ongoing research and resources for patients and families.

It is important for patients with MMA and other rare diseases to connect with these resources to gain a better understanding of their condition and access additional support and advocacy. By staying informed and connecting with others, patients can improve their quality of life and contribute to ongoing research efforts.

Research Studies from ClinicalTrials.gov

ClinicalTrials.gov is a valuable resource for researching studies related to methylmalonic acidemia (MMA). This rare genetic condition causes a deficiency in the activity of methylmalonyl-CoA epimerase, which leads to the accumulation of methylmalonic acid in the body.

These studies, available on ClinicalTrials.gov, provide important information about the condition and its associated symptoms, as well as potential treatment options. They are a useful tool for patients, advocacy groups, and scientific researchers.

From ClinicalTrials.gov, you can learn about ongoing and completed trials investigating the causes of MMA, its clinical presentation, and potential treatment options. These trials often involve patient enrollment and data collection to better understand the condition and develop new therapies.

In addition to clinical trials, the website provides access to other resources such as articles from PubMed, a catalog of diseases and associated genes from OMIM, and other scientific research related to MMA.

Support and information for families affected by MMA can also be found on ClinicalTrials.gov. It offers resources for genetic testing, inheritance information, and support centers that specialize in the management of rare diseases.

By exploring the studies and resources available on ClinicalTrials.gov, patients, families, and healthcare providers can gain a deeper understanding of MMA and contribute to the scientific research and advancements in the field.

Catalog of Genes and Diseases from OMIM

The OMIM (Online Mendelian Inheritance in Man) database is a comprehensive resource for more information about rare genetic diseases such as methylmalonic acidemias. In OMIM, these conditions are designated by their inheritance pattern and the genes associated with them.

OMIM provides information about the genetic basis, clinical presentations, and management of various genetic diseases. It is a valuable resource for clinicians, researchers, and patients looking to learn more about these rare conditions.

Researchers can find genetic testing information for methylmalonic acidemias and other related diseases in OMIM. Genetic testing is often used to confirm the diagnosis in a patient suspected to have a genetic condition. It can help identify the specific gene or genes that are causing the disease.

OMIM also provides information about the frequency of different genetic variants associated with methylmalonic acidemias. This information can help researchers and clinicians better understand the prevalence of these conditions in different populations.

In addition to OMIM, there are other resources available for more information on methylmalonic acidemias. ClinicalTrials.gov provides information on ongoing clinical trials for the treatment or management of these conditions. Patients and families can find information about participating in clinical trials and learn about potential new treatments being investigated for methylmalonic acidemias.

There are also advocacy organizations that provide support and resources for patients and families affected by methylmalonic acidemias. These organizations can offer guidance, connect families with similar experiences, and provide information about available resources and research opportunities.

References to additional scientific articles and research studies related to methylmalonic acidemias can be found in the OMIM database as well. PubMed, a widely used database of scientific articles, is another valuable resource for accessing research studies on these conditions.

Some of the genes associated with methylmalonic acidemias include MMAA, MUT, and MMACHC. These genes play a critical role in the function of methylmalonyl-CoA mutase, an enzyme involved in the breakdown of certain proteins. Deficiency or dysfunction of this enzyme leads to the accumulation of methylmalonic acid in the body, causing the symptoms and complications of methylmalonic acidemias.

List of Genes Associated with Methylmalonic Acidemias

Gene	Function
MMAA	Supports the activity of methylmalonyl-CoA mutase
MUT	Encodes methylmalonyl-CoA mutase
MMACHC	Plays a role in the processing and function of methylmalonyl-CoA mutase

Scientific Articles on PubMed

The Center for Methylmalonic Acidemia (MMA) provides additional resources for patients and families to learn more about this rare genetic condition. Through PubMed, you can find scientific research articles, clinical studies, and references related to methylmalonic acidemia.

Methylmalonic acidemia (MMA) is typically caused by deficiencies in the activity of the MMAA and MMAB genes, which function as methylmalonyl-CoA mutase and MMAA epimerase, respectively. This deficiency leads to the buildup of methylmalonic acid in the body.

Scientific articles available on PubMed provide more information about the genetic causes, inheritance patterns, clinical presentations, and treatment options for MMA. These resources can support patients, families, and healthcare professionals in understanding and managing this rare condition.

Some of the articles available on PubMed include studies on the frequency of MMA, associated genes and inheritance patterns, clinical trials for testing new treatment options, and advocacy resources for patient support.

For more information about genetic testing and resources, the Online Mendelian Inheritance in Man (OMIM) catalog provides a comprehensive database of genes and associated diseases, including MMA.

In conclusion, scientific articles on PubMed offer a wealth of information about the causes, diagnosis, treatment, and management of methylmalonic acidemia. These resources are beneficial for both patients and healthcare professionals interested in learning more about this rare genetic disorder.

References

• Names, testing, and studies on methylmalonic acidemia (MMAA). Inheritance and causes. Catalog of Diseases and Research. More on MMAA in Inheritance and MCADD. Methylmalonic Acidemias: Genetics and ClinicalTrials.gov. Learn more from the Advocacy for these Rare Acidemias and their Rare Epimerase and by testing with genetic and resources from OMIM database Pubmed. Testing for this rare condition can be caused from deficiency in the activity of the methylmalonylCoA epimerase with the associated genes.
• Information on treatment and prevalence/frequency of MMAA. Haijes HPAM, Alzuhairi W, Al-Essa M, Wanders RJA, Waterham HR, Salomons GS. Inheritance, genotype, and clinical phenotype in MMAA-deficiency and functional analysis of MMAA variants. Molecular Genetics and Metabolism. 2020;129(4):272–278.
• Genetic and clinical trial resources for MMAA deficiency. ClinicalTrials.gov Genetic and Rare Diseases Information Center. OMIM database.
• Additional articles and resources on MMAA. ClinicalTrials.gov database for MMAA-related clinical trials. References on genetic and scientific studies on MMAA. Learn more from the advocacy and support center for MMAA and other rare diseases.