glutaric acidemia, GCDH-related

What Is Glutaric Acidemia, GCDH-Related?

Glutaric acidemias are a group of disorders in which glutaric acid is found in high concentrations in the urine. Glutaric acidemia, GCDH-related (a.k.a. glutamic acidemia type 1, or GA I) is an inherited metabolic disease in which the body lacks an enzyme to properly break down the amino acids lysine and tryptophan. The buildup of these amino acids in the body can result in brain damage that impairs movement as well as intellectual function. GA I is caused by mutations in the GCDH gene.

The type and severity of symptoms in individuals with GA I can vary widely. A small number of individuals with GA I have no symptoms at all, while others have severe movement problems and/or intellectual and developmental disabilities.

About 75% of infants with GA I will have an enlarged head also known as macrocephaly, although this feature is not specific to GA I and can make diagnosis difficult. In most children, additional symptoms appear between 6 and 18 months of age typically as the result of a challenge to the body such as an illness with fevers. However, in some cases, there is no identifiable cause of symptoms. Glutaric acid accumulation in the basal ganglia of the brain can result in a severe and permanent loss of motor skills, though intellect often remains normal.

Additional symptoms typically present as a “metabolic crisis,” an episode marked by low blood sugar, excess acid levels, 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 jerky muscle movements, seizures, swelling and bleeding of the brain, coma, and death in some cases. Some children develop bleeding in the brain or eyes; which has been mistaken for child abuse. 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.

How Common Is Glutaric Acidemia, GCDH-Related?

Approximately 1 in 50,000 individuals in the United States is affected by GA I. The prevalence of GA I worldwide is 1 in 100,000 individuals. It is more common in certain ethnicities and communities. Among Old Order Amish in Pennsylvania and the Ojibwa tribe in Canada, as many as 1 in 300 newborns are affected by GA I.

How Is Glutaric Acidemia, GCDH-Related Treated?

Individuals with GA I often have a specific treatment plan devised with the help of metabolic specialists. Often these plans include a low-protein diet, lysine-free formula, and carnitine supplementation. Diets will need to be carefully structured to both avoid problem foods and ensure proper nutrition.

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 treatment to reduce fevers, nausea, and diarrhea. Intravenous fluids and a gastric feeding tube may be used to maintain hydration and nutrition. A high-energy carbohydrate diet, removal of proteins from the diet for 24 to 48 hours, vitamins and additional supplements, and, in some cases, dialysis may also be necessary to prevent a metabolic crisis.

As children get older, the disease is often easier to manage and the risk of metabolic crises will lessen. However, many will still need lifelong dietary treatment. Physical and occupational therapy can also be useful.

What Is the Prognosis for an Individual with Glutaric Acidemia, GCDH-Related?

If the disease is identified early and treated properly, infants with GA I can have normal or near-normal motor and intellectual development. However, even with careful treatment, about 25 to 35% of individuals with GA I develop significant motor problems and other symptoms, even without a metabolic crisis.

Children who have already had a metabolic crisis are likely to develop permanent brain damage that causes severe motor difficulties and involuntary spastic movement. The disease can be fatal in children who go untreated during a metabolic crisis. The 20-year survival rate in children with severe motor and other disabilities is 50%.