Reviewed March 2007
What is the official name of the HADH gene?
The official name of this gene is “hydroxyacyl-Coenzyme A dehydrogenase.”
HADH is the gene's official symbol. The HADH gene is also known by other names, listed below.
What is the normal function of the HADH gene?
The HADH gene provides instructions for making an enzyme called 3-hydroxyacyl-coenzyme A (CoA) dehydrogenase that is important for converting certain fats to energy. Through a process called fatty acid oxidation, several enzymes work in a step-wise fashion to break down (metabolize) fats and convert them to energy. The role of 3-hydroxyacyl-CoA dehydrogenase in this process is to metabolize groups of fats called medium-chain fatty acids and short-chain fatty acids. These fatty acids are found in foods such as milk and certain oils and are produced when larger fatty acids are metabolized.
3-hydroxyacyl-CoA dehydrogenase functions in mitochondria, the energy-producing centers within cells. It is found in mitochondria of the heart, liver, kidneys, muscles, and pancreas. The pancreas provides enzymes that help digest food, and it also produces insulin, which controls how much sugar is passed from the blood into cells for conversion to energy.
3-hydroxyacyl-CoA dehydrogenase is essential for converting medium-chain and short-chain fatty acids to the major source of energy used by the heart and muscles. During prolonged periods without food (fasting) or when energy demands are increased, this energy source is also important for the liver and other tissues.
How are changes in the HADH gene related to health conditions?
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3-hydroxyacyl-coenzyme A dehydrogenase deficiency - caused by mutations in the HADH gene
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Researchers have identified a few mutations in the HADH gene that cause 3-hydroxyacyl-coenzyme A dehydrogenase deficiency. These mutations replace one of the building blocks (amino acids) used to make the 3-hydroxyacyl-CoA dehydrogenase enzyme with an incorrect amino acid. These changes probably alter the 3-dimensional shape of the enzyme, which impairs its normal function.
With a shortage (deficiency) of functional 3-hydroxyacyl-CoA dehydrogenase, medium-chain and short-chain fatty acids are not metabolized properly. As a result, these fats are not converted to energy, which can lead to signs and symptoms of 3-hydroxyacyl-coenzyme A dehydrogenase deficiency such as lack of energy (lethargy) and low blood sugar. Medium-chain and short-chain fatty acids or partially metabolized fatty acids may build up in tissues and damage the liver, heart, and muscles, causing more serious complications.
- other disorders - caused by mutations in the HADH gene
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Mutations in the HADH gene have been reported in a small number of cases of a disorder called familial hyperinsulinemic hypoglycemia. This disorder is characterized by abnormally high levels of insulin and unusually low levels of blood sugar.
Researchers have identified three HADH mutations that severely reduce 3-hydroxyacyl-CoA dehydrogenase activity, either by impairing the enzyme's function or by decreasing the amount of this enzyme in cells. One mutation changes one of the building blocks (amino acids) used to make this enzyme. Specifically, the amino acid proline is replaced with the amino acid leucine at position 258 (written as Pro258Leu). This mutation probably alters the 3-dimensional shape of the 3-hydroxyacyl-CoA dehydrogenase enzyme, which makes it unstable. Another mutation deletes a small section of the HADH gene, which likely leads to an unstable enzyme that is missing 30 amino acids. These unstable versions of 3-hydroxyacyl-CoA dehydrogenase rapidly decay or, if present, have severely reduced activity. Another type of mutation disrupts how information from the HADH gene is spliced together to make a blueprint for the production of 3-hydroxyacyl-CoA dehydrogenase. The resulting blueprint is distorted, which reduces production of the enzyme. Researchers believe that inadequate 3-hydroxyacyl-CoA dehydrogenase activity in the pancreas leads to impaired control of insulin and blood sugar levels.
Where is the HADH gene located?
Cytogenetic Location: 4q22-q26
Molecular Location on chromosome 4: base pairs 109,130,388 to 109,175,779
The HADH gene is located on the long (q) arm of chromosome 4 between positions 22 and 26.
More precisely, the HADH gene is located from base pair 109,130,388 to base pair 109,175,779 on chromosome 4.
See How do geneticists indicate the location of a gene? in the Handbook.
Where can I find additional information about HADH?
You and your healthcare professional may find the following resources about HADH helpful.
- Educational resources - Information pages
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Gene Tests - DNA tests ordered by healthcare professionals (2 links)
You may also be interested in these resources, which are designed for genetics professionals and researchers.
- PubMed - Recent literature
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OMIM - Genetic disorder catalog (2 links)
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What other names do people use for the HADH gene or gene products?
- HAD
- HADH1
- HADHSC
- HCDH_HUMAN
- HHF4
- L-3-hydroxyacyl-Coenzyme A dehydrogenase
- L-3-hydroxyacyl-Coenzyme A dehydrogenase, short chain
- medium and short chain L-3-hydroxyacyl-coenzyme A dehydrogenase
- MGC8392
- M/SCHAD
- SCHAD
- short chain 3-hydroxyacyl-CoA dehydrogenase
Where can I find general information about genes?
The Handbook provides basic information about genetics in clear language.
These links provide additional genetics resources that may be useful.
What glossary definitions help with understanding HADH?
The resources on this site should not be used as a substitute for
professional medical care or advice. Users seeking information about
a personal genetic disease, syndrome, or condition should consult with a qualified
healthcare professional.
See How can I find a genetics professional in my area? in the Handbook.