Glutaric Acidemia Type I

Glutaric acidemia type I is an inherited disorder in which the body is unable to process certain proteins properly. People with this disorder have inadequate levels of an enzyme that helps break down the amino acids lysine, hydroxylysine, and tryptophan, which are building blocks of protein. Excessive levels of these amino acids and their intermediate breakdown products can accumulate and cause damage to the brain, particularly the basal ganglia, which are regions that help control movement. Mental retardation may also occur.

The severity of glutaric acidemia type I varies widely; some individuals are only mildly affected, while others have severe problems. In most cases, signs and symptoms first occur in infancy or early childhood, but in a small number of affected individuals, the disorder first becomes apparent in adolescence or adulthood.

Some babies with glutaric acidemia type I are born with unusually large heads (macrocephaly). Affected individuals may have difficulty moving and may experience spasms, jerking, rigidity, or decreased muscle tone. Some individuals with glutaric acidemia have developed bleeding in the brain or eyes that could be mistaken for the effects of child abuse. Strict dietary control may help limit progression of the neurological damage. Stress caused by infection, fever or other demands on the body may lead to worsening of the signs and symptoms, with only partial recovery.

How common is glutaric acidemia type I?

Glutaric acidemia type I occurs in approximately 1 of every 30,000 to 40,000 individuals. It is much more common in the Amish community and in the Ojibwa population of Canada, where up to 1 in 300 newborns may be affected.

What genes are related to glutaric acidemia type I?

Mutations in the GCDH gene cause glutaric acidemia type I.

The GCDH gene provides instructions for making the enzyme glutaryl-CoA dehydrogenase. This enzyme is involved in processing the amino acids lysine, hydroxylysine, and tryptophan.

Mutations in the GCDH gene prevent production of the enzyme or result in the production of a defective enzyme that cannot function. This enzyme deficiency allows lysine, hydroxylysine and tryptophan and their intermediate breakdown products to build up to abnormal levels, especially at times when the body is under stress.

The intermediate breakdown products resulting from incomplete processing of lysine, hydroxylysine, and tryptophan can damage the brain, particularly the basal ganglia, causing the signs and symptoms of glutaric acidemia type I.

Read more about the GCDH gene.

How do people inherit glutaric acidemia type I?

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 treatment for glutaric acidemia type I?

These resources address the management of glutaric acidemia type I and may include treatment providers.

• Genetic Alliance
• The Organic Acidemias: An Overview

You might also find information on treatment of glutaric acidemia type I in Educational resources and Patient support.

Where can I find additional information about glutaric acidemia type I?

You may find the following resources about glutaric acidemia type I helpful. These materials are written for the general public.

• MedlinePlus - Health information (3 links)
• Educational resources - Information pages (8 links)
• Patient support - For patients and families (5 links)

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

• Gene Reviews - Clinical summary
• Gene Tests - DNA tests ordered by healthcare professionals
• ACTion Sheets - Newborn screening follow up (1 link)
• PubMed - Recent literature
• OMIM - Genetic disorder catalog

What other names do people use for glutaric acidemia type I?

• GA I
• Glutaric acidemia I
• Glutaric acidemia type 1
• Glutaric aciduria I
• Glutaryl-CoA dehydrogenase deficiency

See How are genetic conditions and genes named? in the Handbook.

What if I still have specific questions about glutaric acidemia type I?

• See How can I find a genetics professional in my area? in the Handbook.
• Ask the Genetic and Rare Diseases Information Center.
• Submit your question to Ask the Geneticist.

Where can I find general information about genetic conditions?

The Handbook provides basic information about genetics in clear language.

• What does it mean if a disorder seems to run in my family?
• What are the different ways in which a genetic condition can be inherited?
• If a genetic disorder runs in my family, what are the chances that my children will have the condition?
• Why are some genetic conditions more common in particular ethnic groups?

These links provide additional genetics resources that may be useful.

• Genetics and health
• Resources for Patients and Families
• Resources for Health Professionals

What glossary definitions help with understanding glutaric acidemia type I?

acids ; aciduria ; amino acid ; autosomal ; autosomal recessive ; cell ; CoA ; decreased muscle tone ; deficiency ; dehydrogenase ; enzyme ; fever ; gene ; infection ; macrocephaly ; mental retardation ; muscle tone ; mutation ; neurological ; newborn screening ; population ; progression ; protein ; recessive ; screening ; sign ; stress ; symptom

You may find definitions for these and many other terms in the Genetics Home Reference Glossary.