The PDHA1 gene is responsible for encoding the E1-alpha subunit of the pyruvate dehydrogenase complex. This complex is essential for the conversion of pyruvate to acetyl-CoA, which is a crucial step in energy production within cells. Deficiency in the PDHA1 gene can lead to a metabolic disorder known as pyruvate dehydrogenase complex deficiency (PDCD).

PDCD is an X-linked genetic disorder that primarily affects males, although rare cases have been reported in females. This condition is characterized by a wide range of symptoms, including Leigh syndrome, for which it is a major genetic cause. Leigh syndrome is a progressive neurodegenerative disorder that affects the central nervous system, resulting in movement problems and other health complications.

Tests for PDHA1 gene mutations can be done through genetic testing. Many resources like OMIM and PubMed provide additional information on this gene, its function, and related diseases. The OMIM database lists the PDHA1 gene, along with other genes and proteins related to various genetic conditions.

Citation: GeneTests GeneReview PDHA1-Related Pyruvate Dehydrogenase Deficiency. Retrieved from https://www.ncbi.nlm.nih.gov/books/NBK1115/

Health Conditions Related to Genetic Changes

• PDHA1 gene, also known as pyruvate dehydrogenase E1-alpha component gene, is responsible for encoding the E1-alpha component of the pyruvate dehydrogenase complex.
• Genetic changes in the PDHA1 gene can lead to pyruvate dehydrogenase deficiency, a condition characterized by the buildup of pyruvate, a product of glucose metabolism, in cells.
• Pyruvate dehydrogenase deficiency is associated with various health conditions, including:

• These conditions can cause neurological problems, intellectual disability, seizures, and other related symptoms.
• Testing for genetic changes in the PDHA1 gene can be done through genetic tests, such as sequencing or deletion/duplication analysis.
• For more information on these health conditions and genetic changes in the PDHA1 gene, references to scientific articles, databases, and resources can be found in the following sources:

1. Online Mendelian Inheritance in Man (OMIM): https://www.omim.org/
2. GeneReviews: https://www.ncbi.nlm.nih.gov/books/NBK1116/
3. PubMed: https://pubmed.ncbi.nlm.nih.gov/
4. Genetic Testing Registry: https://www.ncbi.nlm.nih.gov/gtr/

It is important to consult with a healthcare professional or genetic counselor for further information and guidance on genetic testing and these health conditions.

Pyruvate dehydrogenase deficiency

Pyruvate dehydrogenase deficiency is a rare genetic disorder that affects the pyruvate dehydrogenase complex, which is an important component in the metabolic process that converts pyruvate into acetyl-CoA. This complex is composed of multiple proteins, with the E1-alpha subunit being encoded by the PDHA1 gene.

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People with pyruvate dehydrogenase deficiency have problems with this metabolic reaction, leading to a range of neurological and developmental problems. There are several types of pyruvate dehydrogenase deficiency, including the most common X-linked form caused by mutations in the PDHA1 gene. Females can be carriers of the X-linked form but are generally less severely affected than males.

For genetic testing, various resources and databases are available to identify genetic variants associated with pyruvate dehydrogenase deficiency. These resources include the GeneTests database, OMIM (Online Mendelian Inheritance in Man), PubMed, and various other scientific databases and articles. These databases provide information on genetic changes, disease names, and related conditions, as well as references to articles and scientific literature.

The PDHA1 gene encodes the E1-alpha subunit of the pyruvate dehydrogenase complex. Mutations in this gene can disrupt the function of the complex, leading to decreased or absent enzyme activity. This can result in a buildup of pyruvate and a deficiency in acetyl-CoA production, causing energy imbalance and neurological symptoms.

The symptoms of pyruvate dehydrogenase deficiency can vary widely depending on the severity of the genetic changes and the specific mutations involved. Common symptoms include developmental delays, intellectual disabilities, seizures, muscle weakness, and Leigh syndrome, which is a severe neurological disorder.

Pyruvate dehydrogenase deficiency can be diagnosed through a combination of clinical symptoms, biochemical testing, and genetic analysis. Biochemical testing involves measuring enzyme activity levels in cells or tissues, while genetic analysis can identify mutations in the PDHA1 gene. Additional testing may be necessary to rule out other related diseases.

Management of pyruvate dehydrogenase deficiency typically involves a multidisciplinary approach and may include dietary modifications, medications, and supportive therapies. Genetic counseling and prenatal testing are also available for families affected by this condition.

Overall, pyruvate dehydrogenase deficiency is a complex genetic disorder with significant health implications. The availability of databases, genetic testing resources, and scientific articles provides valuable information for researchers, healthcare providers, and affected individuals.

Leigh syndrome

Leigh syndrome is a neurological disorder that is characterized by progressive neurological deterioration, typically beginning in infancy or early childhood. It is named after Denis Archibald Leigh, the British neuropathologist who first described the condition in 1951.

Symptoms:

• Developmental delay
• Loss of previously acquired motor skills
• Weakness and lack of muscle tone
• Dystonia (involuntary muscle contractions)
• Ataxia (impaired balance and coordination)
• Respiratory distress
• Seizures

Genetic component:

Leigh syndrome can be caused by mutations in various genes, including the PDHA1 gene. The PDHA1 gene provides instructions for producing an enzyme called pyruvate dehydrogenase E1-alpha subunit, which is a component of the pyruvate dehydrogenase complex. This complex is responsible for a crucial reaction that helps convert sugar from food into energy for cells. Mutations in the PDHA1 gene result in the production of a nonfunctional or reduced-functioning enzyme, leading to a deficiency in the pyruvate dehydrogenase complex and impaired energy production in cells.

Diagnosis:

Diagnosis of Leigh syndrome involves a combination of clinical features, genetic testing, and imaging studies. Genetic testing can identify mutations in the PDHA1 gene and other genes associated with Leigh syndrome. Imaging studies, such as brain MRI, can reveal characteristic features of the disease, including abnormal signals in specific brain regions.

Treatment:

Currently, there is no cure for Leigh syndrome, and treatment focuses on managing symptoms and providing supportive care. This may include physical, occupational, and speech therapy, as well as medications to control seizures and respiratory problems.

Resources for additional information:

• Genetics Home Reference: PDHA1 gene
• PubMed articles related to PDHA1 gene
• OMIM entry on Leigh syndrome
• GeneTests entry for PDHA1 gene

Other Names for This Gene

This gene is also known by the following names:

• PDHA1
• Pyruvate dehydrogenase E1-alpha subunit
• Pyruvate dehydrogenase 1 alpha non-phosphorylated monomeric isoform
• Pyruvate dehydrogenase component E1-alpha subunit
• AceE1-alpha
• PDHE1-A
• Pyruvate dehydrogenase (lipoamide) alpha 1
• PDH1A
• PDHE1alpha
• PDH-E1 alpha
• PDHE1A
• Pyruvate dehydrogenase E1-alpha subunit
• Pyruvate dehydrogenase component E1 alpha subunit
• Pyruvate dehydrogenase complex, E1 alpha subcomponent, X-linked (Leigh)

References on this gene can be found in scientific articles and other resources:

• Citation of PubMed articles
• Online Mendelian Inheritance in Man (OMIM) catalog
• Genetic Testing Registry
• Health Conditions related to the PDHA1 gene
• Information on testing and genetic counseling for conditions related to this gene

Additional information on the function, types of variant, and testing for PDHA1 gene can be found in the listed resources.

Additional Information Resources

• Scientific Articles:

  • PDHA1 gene – This gene is responsible for encoding the E1-alpha component of the pyruvate dehydrogenase complex. It plays a crucial role in the neurological function of the body.

  • Leigh Syndrome – PDHA1 gene mutations have been found to be one of the causes of Leigh syndrome. This neurological disorder can result in a variety of health problems.

• Genetic Databases:

  • OMIM (Online Mendelian Inheritance in Man) – This database provides comprehensive information on genes and genetic conditions related to PDHA1 gene mutations.

  • GeneReviews – This resource offers in-depth, expert-authored articles on various genetic diseases, including those caused by PDHA1 gene mutations.

• Testing and Diagnostic Resources:

  • Diagnostic Testing – Genetic tests can be performed to identify mutations in the PDHA1 gene and help diagnose related conditions.

  • Neurological Tests – These tests can assess the impact of PDHA1 gene mutations on neurological function and identify any associated neurological disorders.

• Additional Resources:

  • PDHA1 Gene Registry – The PDHA1 gene registry collects and catalogs information about individuals with PDHA1 gene mutations. It serves as a valuable resource for research and collaboration.

  • PubMed – This scientific database contains a wide range of articles on PDHA1 gene mutations and related conditions.

Tests Listed in the Genetic Testing Registry

The PDHA1 gene is associated with several genetic conditions, including pyruvate dehydrogenase E1-alpha deficiency, Leigh syndrome, and X-linked pyruvate dehydrogenase complex-related neurological problems. To determine if a person has a variant in the PDHA1 gene, genetic testing can be performed. The Genetic Testing Registry provides a comprehensive list of tests related to this gene.

Tests listed in the Genetic Testing Registry include:

• PDHA1 gene testing for pyruvate dehydrogenase E1-alpha deficiency
• PDHA1 gene testing for Leigh syndrome
• PDHA1 gene testing for X-linked pyruvate dehydrogenase complex-related neurological problems

These tests can help identify changes or mutations in the PDHA1 gene, which can affect the function of pyruvate dehydrogenase, a key component of the pyruvate dehydrogenase complex. By understanding the genetic variant present, healthcare professionals can better diagnose and manage these conditions.

In addition to the Genetic Testing Registry, other databases and resources can provide more information about the PDHA1 gene and related conditions. The Online Mendelian Inheritance in Man (OMIM) catalog, PubMed, and scientific articles can provide further references and information about the gene and its associated diseases.

Genetic testing is an important tool in diagnosing and understanding genetic conditions. By identifying changes in specific genes, such as the PDHA1 gene, healthcare professionals can better tailor treatments and management plans for individuals affected by these conditions.

Scientific Articles on PubMed

PubMed is a database that provides access to a large collection of scientific articles related to various topics including genetics, health, and diseases. Here are some scientific articles related to the PDHA1 gene:

• PDHA1 gene: This article provides an overview of the PDHA1 gene, which encodes the E1-alpha component of the pyruvate dehydrogenase complex. It discusses the genetic variations and changes in the PDHA1 gene that can lead to pyruvate dehydrogenase deficiency, a genetic disorder affecting the function of the pyruvate dehydrogenase complex.
• Pyruvate dehydrogenase deficiency: This article focuses on pyruvate dehydrogenase deficiency, a condition caused by mutations in the PDHA1 gene. It discusses the symptoms, diagnostic testing, and treatment options for this metabolic disorder.
• PDHA1 gene variants: This article provides information on different variants of the PDHA1 gene and their impact on pyruvate dehydrogenase function. It discusses how specific PDHA1 gene variants can result in varying degrees of pyruvate dehydrogenase deficiency and associated health problems.

These articles illustrate the importance of the PDHA1 gene and its role in pyruvate dehydrogenase activity. They also highlight the significance of genetic testing and counseling for individuals and families affected by PDHA1 gene mutations. Additional information and resources on related conditions and genetic databases can be found on the Online Mendelian Inheritance in Man (OMIM) website.

Catalog of Genes and Diseases from OMIM

OMIM, or Online Mendelian Inheritance in Man, is a scientific catalog of genes and diseases. It provides complex and detailed information about various genetic conditions and the genes associated with them. This catalog is an invaluable resource for researchers, healthcare professionals, and individuals interested in genetic health.

OMIM offers free access to a vast collection of articles and resources related to genetic diseases. These articles provide comprehensive information about the diseases, including their symptoms, genetic variants, testing methods, and more.

The catalog includes a wide range of genetic conditions, ranging from neurological disorders such as Leigh syndrome to metabolic disorders like pyruvate dehydrogenase E1-alpha deficiency. Each disease is listed with its OMIM number, alternative names, and relevant information about the associated gene.

For each gene, OMIM provides details about its function, amino acid sequence, and its role in various biological processes. It also includes information about the cellular and molecular changes that occur when the gene is defective or mutated.

OMIM references additional resources such as PubMed and Genet, which can be consulted for more in-depth information. These references provide scientific articles, research papers, and other sources that further elucidate the genetic mechanisms and clinical characteristics of the diseases.

In addition to the catalog of genes and diseases, OMIM also maintains a registry of genetic testing laboratories. This registry helps individuals find laboratories that offer testing for specific genetic conditions. It provides important information such as the types of tests offered, availability of testing for males and females, and relevant contact details.

Overall, OMIM is a comprehensive and reliable resource for anyone seeking information about genetic diseases. Its extensive catalog of genes and diseases, coupled with the wealth of scientific articles and testing resources, makes it an indispensable tool in the field of genetics and healthcare.

Gene and Variant Databases

When studying the PDHA1 gene and its associated variants, it is important to have access to reliable and comprehensive gene and variant databases. These databases provide information on the function of the gene, the different variants that have been identified, and their association with various health conditions.

One such database is the OMIM (Online Mendelian Inheritance in Man) database. OMIM provides a catalog of genes and genetic conditions, including information on the PDHA1 gene and its related diseases. It includes names and references for scientific articles, as well as additional resources for further reading.

Another valuable resource is the PubMed database, which provides access to a vast collection of scientific articles. By searching for keywords such as “PDHA1 gene” or “pyruvate dehydrogenase deficiency,” researchers can find relevant articles that discuss the gene and its associated variants.

The PDHA1 gene is listed in various gene and variant databases, including Genetests and the Leigh Syndrome Registry. These databases offer information on the different types of variants that have been identified in the PDHA1 gene, as well as the associated symptoms and health problems.

One of the common variants of the PDHA1 gene is the E1-alpha variant, which leads to a deficiency in the pyruvate dehydrogenase complex. This deficiency affects the enzyme’s ability to convert pyruvate into acetyl-CoA, leading to a buildup of pyruvate and a decrease in energy production within cells.

Genetic testing is available for individuals who suspect they may have a variant in the PDHA1 gene. These tests can help identify changes in the gene’s structure or function, and can provide a diagnosis for conditions such as Leigh syndrome and other neurological diseases.

By utilizing gene and variant databases, researchers and clinicians can access up-to-date information on the PDHA1 gene and its associated variants. This information is crucial for understanding the function of the gene, identifying potential health conditions related to its variants, and developing appropriate testing and treatment strategies.

References:

• “OMIM – PDHA1” – Online Mendelian Inheritance in Man.
• “PubMed” – National Center for Biotechnology Information.
• “Genetests” – University of Washington.
• “Leigh Syndrome Registry” – North American Mitochondrial Disease Consortium.

References

• Leigh Syndrome Registry, Mitochondrial → Pyruvate Dehydrogenase E1-alpha Gene (PDHA1)

  A comprehensive catalog of information on Leigh syndrome, including genetic testing information and a list of genes related to the condition, such as PDHA1.

  Website

• OMIM → PDHA1

  The Online Mendelian Inheritance in Man (OMIM) database provides detailed information about genes, diseases, and other genetic conditions. This page specifically focuses on the PDHA1 gene and its associated disorders.

  Website

• PubMed → PDHA1

  PubMed is a database of scientific articles. This link will display a list of articles related to the PDHA1 gene and its function, as well as the role of PDHA1 in various diseases and conditions.

  Website

• GeneReviews → PDHA1-Related Pyruvate Dehydrogenase Complex Deficiency

  GeneReviews provides comprehensive, peer-reviewed information about genetic disorders. This page focuses on PDHA1-related pyruvate dehydrogenase complex deficiency, including clinical features, diagnosis, and management.

  Website

• Genetics Home Reference → PDHA1 gene

  This resource provides consumer-friendly information about the PDHA1 gene, including its normal function and the health problems that can result from changes in this gene.

  Website