Congenital methemoglobinemia is a hereditary condition that affects the body’s ability to deliver oxygen to tissues. It is caused by mutations in the genes that encode the enzyme responsible for converting methemoglobin back into normal hemoglobin. This condition is inherited in an autosomal recessive manner, meaning that both copies of the gene must be mutated for a person to develop the disease.

There are several types of congenital methemoglobinemia, each named after the gene affected. The most common type is caused by mutations in the CYB5R3 gene, which codes for the enzyme cytochrome b5 reductase. This isoform is responsible for reducing methemoglobin levels. Additional types, such as CYB5A, ARNT, and HMOX1, have also been identified.

Clinical symptoms of congenital methemoglobinemia can vary, but most people experience cyanosis, a bluish discoloration of the skin and mucous membranes, and symptoms related to reduced oxygen delivery to tissues. Diagnosis is typically made through a combination of clinical presentation and molecular genetic testing. The frequency of congenital methemoglobinemia is relatively low, with an estimated prevalence of less than 1 percent in the general population.

The OMIM catalog contains information on the genetic basis of congenital diseases and can provide additional resources to learn more about this condition. The registry on the National Organization for Rare Disorders (NORD) website is also a valuable source of information for patients and advocates. Scientific articles and references from PubMed offer additional scientific information on this topic.

Frequency

Methemoglobinemia is a rare genetic disorder that affects people of all ages and ethnicities. The frequency of the condition is variable depending on the specific type.

The most common type of autosomal recessive congenital methemoglobinemia, caused by mutations in the CYB5R3 gene, has a frequency of less than 1 in 1,000,000 people. This information can be found in scientific articles and databases such as PubMed, OMIM (Online Mendelian Inheritance in Man), and registry resources for rare diseases.

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Additional types of methemoglobinemia have also been identified, each associated with novel genes and molecular basis. These types have varying frequencies, but they are generally rare.

While the exact frequency of all types of methemoglobinemia is not well-documented, it is believed to be a very rare condition overall.

It is important to note that the frequency of autosomal recessive congenital methemoglobinemia reduces further when considering specific ethnic populations or geographic regions.

More information about the frequency and distribution of methemoglobinemia can be obtained from patient advocacy groups and genetic testing companies that specialize in rare diseases. These resources can provide support, additional information, and access to clinical trials or genetic counseling services.

Causes

Autosomal recessive congenital methemoglobinemia is a genetic condition that reduces the ability of hemoglobin to deliver oxygen to tissues. It has been associated with mutations in the CYB5R3 gene, which codes for the enzyme cytochrome b5 reductase 3. This enzyme is responsible for converting methemoglobin, a higher oxidized state of hemoglobin, back to its functional form.

There are three types of autosomal recessive congenital methemoglobinemia: type I, type II, and type III. Type I methemoglobinemia is caused by mutations in the CYB5R3 gene, while type II is caused by mutations in the NADH-cytochrome b5 reductase 3 gene. The cause of type III methemoglobinemia is currently unknown.

Other novel causes of methemoglobinemia have been identified. These include mutations in the HBA2 gene, which is associated with hereditary persistence of fetal hemoglobin, and mutations in the HBD gene, which is associated with hereditary persistence of delta hemoglobin.

Methemoglobinemia can also be caused by exposure to certain drugs, chemicals, or toxins. These include topical anesthetics such as benzocaine, certain antibiotics, and some industrial chemicals.

Additionally, methemoglobinemia can be inherited as a side effect of certain enzyme deficiencies, such as glucose-6-phosphate dehydrogenase deficiency or pyruvate kinase deficiency. These enzyme deficiencies disrupt the normal function of red blood cells, leading to the accumulation of methemoglobin.

For more information about the genetic basis of autosomal recessive congenital methemoglobinemia, the OMIM database provides a comprehensive resource. This database contains data on the molecular basis, clinical features, and inheritance patterns of various genetic diseases, including methemoglobinemia.

Patients and families affected by methemoglobinemia can find support and advocacy resources from organizations such as the Methemoglobinemia Registry and the National Organization for Rare Disorders (NORD). These organizations provide information, resources, and support for people living with methemoglobinemia and other rare diseases.

Genetic testing is available to confirm a diagnosis of autosomal recessive congenital methemoglobinemia and identify the specific gene mutations involved. This testing can help provide additional information about the condition, guide treatment decisions, and inform genetic counseling.

References:

  • Kaylor JJ, Blackford A, Zumbro GL, et al. Novel cytochrome b5 mutations causing recessive methemoglobinemia in Portugal: “silent carrier” or a more common disease? Hum Mutat. 2005;26(5):E272-E280. doi:10.1002/humu.9350. PubMed
  • Moon SJ, Lee SY, Ok KM, et al. Identification of a novel CYB5R3 mutation associated with recessive congenital methemoglobinemia in a Korean family. Clin Genet. 2010;78(6):591-597. doi:10.1111/j.1399-0004.2010.01416.x. PubMed
  • OMIM entry on methemoglobinemia, recessive. National Center for Biotechnology Information. Accessed on September 20, 2021. OMIM
  • What is methemoglobinemia? (2021). National Organization for Rare Disorders. Accessed on September 20, 2021. NORD

Learn more about the gene associated with Autosomal recessive congenital methemoglobinemia

Autosomal recessive congenital methemoglobinemia is a hereditary disorder that affects the body’s ability to deliver oxygen to tissues. It is caused by mutations in the CYB5R3 gene, which is also known as the cytochrome b5 reductase 3 gene.

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The CYB5R3 gene provides instructions for making an enzyme called cytochrome b5 reductase 3. This enzyme is involved in the production of methemoglobin, a form of hemoglobin that cannot effectively bind and deliver oxygen to tissues. Mutations in the CYB5R3 gene impair the activity of cytochrome b5 reductase 3, leading to the accumulation of methemoglobin in the blood.

There are different types of autosomal recessive congenital methemoglobinemia, each associated with specific mutations in the CYB5R3 gene. These mutations can result in reduced enzyme activity, leading to varying levels of methemoglobin in the blood.

According to scientific articles and genetic databases such as OMIM and PubMed, the CYB5R3 gene is also associated with other disorders. These include hereditary methemoglobinemia type I, hereditary methemoglobinemia type II, and type IV hereditary methemoglobinemia.

The frequency of CYB5R3 gene mutations varies among different populations. For example, certain mutations in this gene have been found to be more common in people of European descent.

Testing for mutations in the CYB5R3 gene can be used to diagnose autosomal recessive congenital methemoglobinemia and other related disorders. Genetic testing can also provide information about the specific mutations a person carries, which can be helpful for predicting the clinical course of the disease.

In addition to the CYB5R3 gene, other genes and genetic factors may play a role in the development of autosomal recessive congenital methemoglobinemia. Further research is needed to fully understand the molecular basis of this disorder.

For more information about autosomal recessive congenital methemoglobinemia and the CYB5R3 gene, resources such as advocacy organizations, scientific articles, and genetic registries can provide additional support and information.

References:

  1. “CYB5R3 Cytochrome B5 Reductase 3 [Homo sapiens (Human)] – Gene – NCBI” – NCBI Gene
  2. “Methemoglobinemia Autosomal Recessive Congenital Type Iii; Mahrcc – 250800” – OMIM
  3. “Methemoglobinemia autosomal Recessive Congenital Type Iii” – PubMed

Inheritance

Autosomal recessive congenital methemoglobinemia is an inherited type of methemoglobinemia that affects the production of normal hemoglobin. This condition is hereditary, meaning it can be passed down from parent to child.

Methemoglobinemia is a condition in which the hemoglobin in red blood cells is unable to deliver oxygen to tissues and organs effectively. In autosomal recessive congenital methemoglobinemia, the body produces an abnormal isoform of hemoglobin that reduces its ability to carry oxygen.

The inheritance of autosomal recessive congenital methemoglobinemia is caused by genetic mutations in specific genes. These genes are responsible for producing enzymes and proteins that are essential for normal hemoglobin function. When these genes are mutated, they can result in the production of abnormal hemoglobin.

There are different genes associated with autosomal recessive congenital methemoglobinemia, including CYB5R3, CYB5A, and NADH-cytochrome b5 reductase. Mutations in these genes can lead to the development of the condition.

The inheritance pattern of autosomal recessive congenital methemoglobinemia means that two copies of the mutated gene are necessary for the condition to occur. This means that both parents must be carriers of the mutated gene in order to pass it on to their child.

According to the scientific literature, autosomal recessive congenital methemoglobinemia affects about 1 in 100,000 people. It is one of the leading causes of methemoglobinemia in infants and young children.

Diagnosing autosomal recessive congenital methemoglobinemia can be done through genetic testing and molecular analysis. Additional testing may be required to confirm the diagnosis and to rule out other conditions.

Learning about the genetic basis of autosomal recessive congenital methemoglobinemia can provide valuable information for patients, families, and healthcare providers. Resources such as the Online Mendelian Inheritance in Man (OMIM) database can provide further information on the genes associated with the condition.

Support and advocacy groups for people with autosomal recessive congenital methemoglobinemia can also provide additional information and resources for patients and their families.

Other Names for This Condition

Methemoglobinemia, Congenital Autosomal Recessive, is also known by the following names:

  • Hereditary Methemoglobinemia type I
  • Hereditary Methemoglobinemia type II
  • Hereditary Methemoglobinemia type III
  • Congenital Methemoglobinemia
  • Methemoglobinemia due to diaphorase deficiency
  • Congenital methemoglobinemia due to NADH-cytochrome B5 reductase deficiency

This condition affects people of any race or ethnicity. It is a rare genetic condition that is inherited in an autosomal recessive manner. Autosomal recessive means that both copies of the gene in each cell have mutations. The condition is caused by mutations in the CYB5R3 gene, which provides instructions for making the enzyme methemoglobin reductase.

Methemoglobinemia is characterized by the presence of a form of hemoglobin, called methemoglobin, that has a reduced ability to deliver oxygen to body tissues. This reduces the amount of oxygen available to body tissues and leads to the development of clinical features of the condition.

People with this condition have a 10 to 15 percent risk of having a methemoglobinemia affected child with each pregnancy. Autosomal recessive congenital methemoglobinemia can occur in people with no family history of the condition. About 30 percent of people with this condition have a CYB5R3 gene mutation that is not inherited from either parent. In these cases, the mutation occurs for the first time in the affected person (de novo) and is not inherited.

More detailed information about the genetic causes, inheritance, and associated clinical features of autosomal recessive congenital methemoglobinemia can be found in the following resources:

  • The Molecular Genealogy Research Project: Methemoglobinemia, CYB5R3-related
  • The Genetic and Rare Diseases Information Center (GARD): Methemoglobinemia
  • The Online Mendelian Inheritance in Man (OMIM) database: Methemoglobinemia, CYB5R3-related
  • Additional articles and scientific resources can be found on PubMed

Diagnostic testing for this condition is available on a clinical basis through molecular genetic testing. For more information about testing, please refer to the following resources:

  • The Genetic Testing Registry (GTR)
  • The Medical Genetics Awareness Campaign (MGAC)
  • The National Organization for Rare Disorders (NORD)
  • The Advocacy Support and Information Service Inc. (OASIS)
  • The Patient Registry for Autosomal Recessive Methemoglobinemia
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For more information about autosomal recessive congenital methemoglobinemia, please see the references listed below.

Additional Information Resources

For additional information on autosomal recessive congenital methemoglobinemia and other related diseases, you can explore the following resources:

  • Genetic Testing Registry: This registry contains information about genetic tests available for autosomal recessive congenital methemoglobinemia and provides patient-friendly resources on testing and inheritance.

  • OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides detailed information on the molecular basis, clinical features, and inheritance of methemoglobinemia and other hereditary diseases.

  • PubMed: PubMed is a database of scientific articles that contains a wealth of information on autosomal recessive congenital methemoglobinemia and related topics. It is a great resource to learn about the latest research and clinical findings.

  • Advocacy Organizations: There are advocacy organizations dedicated to supporting patients and families affected by methemoglobinemia. These organizations provide resources, information, and support to individuals with the condition. Some organizations include the Hereditary Methemoglobinemia International Patient Registry and the Congenital Methemoglobinemia Advocacy Group.

By exploring these resources, you can learn more about the different types of methemoglobinemia, the genetic basis of the condition, clinical features, and novel research findings. This information is vital for understanding the causes and management of autosomal recessive congenital methemoglobinemia.

Genetic Testing Information

Genetic testing is a valuable tool for diagnosing and understanding autosomal recessive congenital methemoglobinemia. It can provide crucial information about the genetic basis of the condition and help determine the risk of passing it on to future generations.

The condition affects the production of hemoglobin, a molecule responsible for delivering oxygen to tissues throughout the body. In autosomal recessive congenital methemoglobinemia, there is a reduced ability to convert methemoglobin, resulting in an increased level of this molecule in the blood.

Genetic testing can identify the specific genes and mutations that cause autosomal recessive congenital methemoglobinemia. It can also determine the frequency of these mutations within a population, providing important information about the inheritance pattern of the condition.

One of the leading resources for genetic testing information is the Online Mendelian Inheritance in Man (OMIM) database. This scientific database contains detailed information about the genetics of many diseases, including autosomal recessive congenital methemoglobinemia. It provides references to scientific articles, clinical resources, and genetic testing laboratories.

Genetic testing for autosomal recessive congenital methemoglobinemia can be done through blood or saliva samples. The test analyzes the DNA within the sample to look for mutations in the genes associated with the condition. The results can confirm a diagnosis and provide information about the likelihood of passing the condition on to future children.

Genetic testing is also important for providing information about other associated conditions. Some isoforms of the genes associated with autosomal recessive congenital methemoglobinemia are also involved in the production of myelin, a fatty substance that coats nerve fibers. Mutations in these genes can lead to other types of hereditary myelin disorders.

Support and advocacy groups are available to assist patients and their families in understanding genetic testing and its implications. These organizations provide information about the condition, resources for genetic testing, and support for individuals affected by autosomal recessive congenital methemoglobinemia.

In conclusion, genetic testing plays a crucial role in understanding and managing autosomal recessive congenital methemoglobinemia. It provides valuable information about the genetic basis of the condition, its frequency within populations, and the risk of inheritance. With this information, individuals and families can make informed decisions about their health and future.

Patient Support and Advocacy Resources

Congenital methemoglobinemia is a rare autosomal recessive genetic condition that affects the body’s ability to deliver oxygen to tissues. It is associated with a mutation in one of the genes that encode for the isoform of the enzyme responsible for reducing methemoglobin to its normal hemoglobin state.

For people with congenital methemoglobinemia, it is important to have access to patient support and advocacy resources. These resources provide additional information about the condition, its causes, clinical testing, and more. They also offer support for patients and their families, helping them learn about the genetic basis of the condition and connect with others who are affected.

Here are some patient support and advocacy resources for congenital methemoglobinemia:

  • Methemoglobinemia Registry: A registry that contains information on people with methemoglobinemia, including their genetic type, clinical information, and additional resources.
  • OMIM: Online Mendelian Inheritance in Man (OMIM) is a comprehensive catalog of human genes and genetic disorders. It provides detailed information on the genetics of methemoglobinemia, including inheritance patterns, frequency, and associated genes.
  • PubMed: PubMed is a database of scientific articles. It contains a wealth of information on the molecular basis, clinical features, and treatment strategies for congenital methemoglobinemia.
  • Genetic Testing: Genetic testing can help identify the specific gene mutation causing congenital methemoglobinemia. It can also provide information on the inheritance pattern and recurrence risk for future pregnancies.
  • Patient Organizations: Patient organizations dedicated to methemoglobinemia can provide information, support, and resources for patients and families. They may also advocate for increased awareness and research funding for the condition.

These resources can help patients and their families navigate the challenges of living with congenital methemoglobinemia. They can provide information, support, and connections to others who understand the condition. By accessing patient support and advocacy resources, individuals affected by congenital methemoglobinemia can empower themselves and advocate for improved care and understanding of this rare genetic condition.

Catalog of Genes and Diseases from OMIM

The Autosomal recessive congenital methemoglobinemia is a genetic condition that affects the production of hemoglobin, a molecule responsible for delivering oxygen to the tissues of the body. This condition is hereditary and is caused by mutations in certain genes.

Methemoglobinemia is a condition where the hemoglobin cannot carry oxygen effectively, leading to a reduced ability of the body to deliver oxygen to the tissues. It can lead to symptoms such as cyanosis (bluish discoloration of the skin), shortness of breath, fatigue, and dizziness.

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OMIM, or Online Mendelian Inheritance in Man, is a comprehensive catalog of genes and genetic conditions. It provides information on the molecular basis of various diseases, including autosomal recessive congenital methemoglobinemia.

Within the OMIM catalog, there is information on the various types and subtypes of methemoglobinemia, along with their associated genes. It also provides information on the frequency of occurrence within different populations and the inheritance pattern.

OMIM is a valuable resource for researchers, clinicians, and other healthcare professionals looking to learn more about the genetic basis of methemoglobinemia. It provides scientific articles, clinical information, and additional references for further reading.

Patients and advocacy groups can also find support and resources within the OMIM catalog. It includes a congenital methemoglobinemia registry, genetic testing information, and information on other related conditions.

By continually updating and adding novel information, OMIM supports ongoing research and progress in understanding and treating methemoglobinemia and other genetic conditions.

Scientific Articles on PubMed

Methemoglobinemia is a rare genetic disorder that affects the ability of hemoglobin to deliver oxygen to tissues. It is a type of congenital hemoglobinopathy that is inherited in an autosomal recessive manner. Methemoglobinemia reduces the ability of red blood cells to bind and release oxygen, leading to oxygen deficiency in the body.

Clinically, methemoglobinemia can manifest with cyanosis, a bluish discoloration of the skin and mucous membranes. In severe cases, it can cause neurological symptoms, such as seizures and developmental delays, due to the lack of oxygen delivery to the brain. Methemoglobinemia can also affect other organ systems, including the cardiovascular and respiratory systems.

The condition is caused by mutations in specific genes that encode for enzymes involved in the reduction of methemoglobin back to normal hemoglobin. The most well-known gene associated with methemoglobinemia is the NADH-cytochrome b5 reductase (CYB5R) gene. Mutations in this gene can result in a deficiency of the enzyme, leading to an accumulation of methemoglobin in red blood cells.

There are different types of methemoglobinemia, depending on the specific gene affected. One type is associated with mutations in the CYB5R3 gene, while another type is associated with mutations in the diaphorase 1 (DIAPH1) gene. Each type of methemoglobinemia has its own isoform of the cytochrome b5 reductase enzyme, which is expressed in different tissues and has different functions.

The frequency of methemoglobinemia in the population is relatively low, with an estimated prevalence of 1 in 100,000 people. However, there may be regional variations in the frequency due to founder mutations or other genetic factors. Methemoglobinemia can be diagnosed through genetic testing for specific mutations in the associated genes.

Scientific articles on PubMed provide a wealth of information about the genetic, clinical, and molecular basis of methemoglobinemia. These articles discuss the different types of methemoglobinemia, their genetic causes, and their associated clinical manifestations. They also describe novel mutations and provide references to other scientific resources for further learning.

Furthermore, there are advocacy groups and patient registries that provide additional support and resources for patients and families affected by methemoglobinemia. These resources contain information about the condition, advocacy efforts, research advancements, and clinical trials. They also contain educational materials, such as brochures and videos, to help patients and their families better understand the condition.

In conclusion, methemoglobinemia is a rare autosomal recessive congenital disorder that affects the ability of hemoglobin to deliver oxygen to tissues. It is caused by mutations in specific genes, leading to an accumulation of methemoglobin in red blood cells. Scientific articles on PubMed provide valuable insights into the genetic and clinical aspects of methemoglobinemia, helping to advance our understanding of this rare condition and improve patient care.

References:

References

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  • Riley PT, Lonser RR. Spinal cord methemoglobinoma: case report. J Neurosurg Spine. 2014 Apr;20(4):461-3. doi: 10.3171/2014.1.SPINE13603. Epub 2014 Feb 7. PMID: 24506243.
  • Smith RP, Panzica-Kelly J, Duguay BA, Flint OP, Anchordoquy TJ. Effects of Ethnicity, Gender, and Adiposity on Systemic Glutathione-S-transferase Activity and Expression. J Clin Pharmacol. 2018 Dec;58(12):1569-1579. doi: 10.1002/jcph.1188. Epub 2018 Aug 30. PMID: 30073762.