Glutaric Acidaemia Type I

What is glutaric acidaemia type I?

Glutaric acidaemia 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 acidaemia type I varies widely; some individuals are only mildly affected, while others have severe problems. Some babies with glutaric acidaemia 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 acidaemia 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 acidaemia type I?

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

What genes are related to glutaric acidaemia type I?

Mutations in the GCDH gene cause glutaric acidaemia 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. They are particularly prone to affect the basal ganglia, causing the signs and symptoms of glutaric acidaemia type I.

How do people inherit glutaric acidaemia type I?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

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

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