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3-methylglutaconyl-CoA hydratase deficiency

3-methylglutaconyl-CoA hydratase deficiency

Reviewed June 2014

What is 3-methylglutaconyl-CoA hydratase deficiency?

3-methylglutaconyl-CoA hydratase deficiency is an inherited condition that causes neurological problems. Beginning in infancy to early childhood, children with this condition often have delayed development of mental and motor skills (psychomotor delay), speech delay, involuntary muscle cramping (dystonia), and spasms and weakness of the arms and legs (spastic quadriparesis). Affected individuals can also have optic atrophy, which is the degeneration (atrophy) of nerve cells that carry visual information from the eyes to the brain.

In some cases, signs and symptoms of 3-methylglutaconyl-CoA hydratase deficiency begin in adulthood, often in a person's twenties or thirties. These individuals have damage to a type of brain tissue called white matter (leukoencephalopathy), which likely contributes to progressive problems with speech (dysarthria), difficulty coordinating movements (ataxia), stiffness (spasticity), optic atrophy, and a decline in intellectual function (dementia).

Affected individuals who show symptoms of 3-methylglutaconyl-CoA hydratase deficiency in childhood often go on to develop leukoencephalopathy and other neurological problems in adulthood.

All people with 3-methylglutaconyl-CoA hydratase deficiency accumulate large amounts of a substance called 3-methylglutaconic acid in their body fluids. As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria). 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with 3-methylglutaconyl-CoA hydratase deficiency also have high urine levels of another acid called 3-methylglutaric acid.

How common is 3-methylglutaconyl-CoA hydratase deficiency?

3-methylglutaconyl-CoA hydratase deficiency is a rare disorder; at least 20 cases have been reported in the scientific literature.

What genes are related to 3-methylglutaconyl-CoA hydratase deficiency?

Mutations in the AUH gene cause 3-methylglutaconyl-CoA hydratase deficiency. This gene provides instructions for producing 3-methylglutaconyl-CoA hydratase, an enzyme that is involved in breaking down a protein building block (amino acid) called leucine to provide energy for cells. This amino acid is broken down in cell structures called mitochondria, which convert energy from food into a form that cells can use.

AUH gene mutations lead to an absence of enzyme activity. Without any functional 3-methylglutaconyl-CoA hydratase, leucine is not properly broken down, which leads to a buildup of related compounds, including multiple acids: 3-methylglutaconic acid, 3-methylglutaric acid, and 3-hydroxyisovaleric acid. Researchers speculate that an accumulation of these acids in the fluid that surrounds and protects the brain and spinal cord (the cerebrospinal fluid or CSF) can damage these structures and contribute to the neurological features of 3-methylglutaconyl-CoA hydratase deficiency.

Because the age at which the condition begins varies widely and because the signs and symptoms improve in some affected children, researchers speculate that other genes or environmental factors may play a role in the features of 3-methylglutaconyl-CoA hydratase deficiency.

Read more about the AUH gene.

How do people inherit 3-methylglutaconyl-CoA hydratase deficiency?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of 3-methylglutaconyl-CoA hydratase deficiency?

These resources address the diagnosis or management of 3-methylglutaconyl-CoA hydratase deficiency and may include treatment providers.

You might also find information on the diagnosis or management of 3-methylglutaconyl-CoA hydratase deficiency in Educational resources and Patient support.

General information about the diagnosis and management of genetic conditions is available in the Handbook. Read more about genetic testing, particularly the difference between clinical tests and research tests.

To locate a healthcare provider, see How can I find a genetics professional in my area? in the Handbook.

Where can I find additional information about 3-methylglutaconyl-CoA hydratase deficiency?

You may find the following resources about 3-methylglutaconyl-CoA hydratase deficiency helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for 3-methylglutaconyl-CoA hydratase deficiency?

  • 3-methylglutaconic aciduria, type I
  • 3-MG-CoA-hydratase deficiency
  • AUH defect
  • MGA1
  • MGA, type I
  • MGCA1
  • primary 3-methylglutaconic aciduria

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines and How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about 3-methylglutaconyl-CoA hydratase deficiency?

Where can I find general information about genetic conditions?

What glossary definitions help with understanding 3-methylglutaconyl-CoA hydratase deficiency?

References (7 links)


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.

Reviewed: June 2014
Published: February 8, 2016