glutaric acidemia type 1

What is Glutaric Acidemia Type 1?

Glutaric acidemia type 1 (GA I) is an inherited metabolic disease in which the body lacks an enzyme to properly break down certain amino acids, the building blocks of protein. When these amino acids build up in the body, a person can develop brain damage that can impair their ability to move as well as their intellectual function.

The type and severity of symptoms in people with GA I can vary widely. A small number of people with genetic mutations that cause the disease have no symptoms at all, while others have severe movement problems and/or mental disability.

In most children, symptoms appear between two months and four years of age. A smaller number do not show symptoms until later, even as late as adulthood. Symptoms appear as a “metabolic crisis,” an episode marked by low blood sugar, vomiting, lack of energy, difficulty feeding, irritability, and poor muscle tone that causes the body to seem floppy. If unrecognized and untreated with a special diet, these episodes can progress to cause spastic and jerking muscle movements, seizures, swelling and bleeding of the brain, coma, and even death. They can often be triggered by illness, fever, or going too long without eating.

In children with GA I, the first metabolic crisis often results in permanent damage to a part of the brain known as the basal ganglia. This damage can result in a severe and permanent loss of motor skills, though often intellect remains normal.

Other children do not experience a metabolic crisis, but show a delay in motor and intellectual development. Children with these symptoms are more likely to have intellectual impairment later in life.

Early diagnosis and strict control of the child’s diet can avert a metabolic crisis and significantly reduce the risk of brain damage and impaired movement ability. Even with careful treatment, however, roughly 25 to 35% of people with GA I develop significant motor problems and other symptoms, even without a metabolic crisis.

Most children with the disease are born with large heads. Some develop bleeding in the brain that has been mistaken for child abuse.

How common is Glutaric Acidemia Type 1?

GA I affects 1 in 40,000 Caucasians. It is more common in certain ethnicities and communities. In Sweden, 1 in 30,000 people have the disease. Among Old Order Amish in Pennsylvania and the Ojibwa tribe in Canada, as many as 1 in 300 children are affected by GA I.

How is Glutaric Acidemia Type 1 treated?

A physician specializing in metabolism should help devise a treatment plan for any child with GA I. Often these plans include vitamins and supplements and frequent meals low in certain proteins. Diets will need to be carefully structured to both avoid problem foods and ensure proper nutrition. In some cases, meals may be necessary around the clock, even overnight. A specialist will also devise a “sick day plan” to use when a child shows signs of illness that could lead to a metabolic crisis. Often this involves frequent meals with carbohydrates and an increased fluid intake, even if the child isn't hungry or thirsty.

As children get older, the disease is often easier to manage and the risk of metabolic crises lessens. Many will still need lifelong dietary treatment, however.

It is believed that those who receive treatment before their first metabolic crisis do better in the long term.

Children who are having a metabolic crisis must be promptly treated, often with intravenous fluids, certain vitamins and supplements, and in some cases, dialysis.

What is the prognosis for a person with Glutaric Acidemia Type 1?

If treated early and carefully, many children with GA I can live healthy lives with normal or near-normal motor and intellectual development. It should be noted, however, that even with treatment, 25 to 35% of children with GA I develop some level of motor and intellectual impairment.

Children who have already had a metabolic crisis are likely to develop permanent brain damage that causes severe motor difficulties and involuntary spastic movement. In children who go untreated during a metabolic crisis, the disease can be fatal.