Glutaric aciduria type 1 (GA1) is an inherited metabolic disorder. It results from an enzyme deficiency that prevents the body from breaking down some amino acids. This causes a buildup of toxic compounds.
A metabolic disorder occurs when abnormal chemical reactions disrupt the body’s metabolism. This can affect the body’s ability to break down certain substances.
GA1 belongs to a group of metabolic disorders known as organic acidemias. These disorders involve a disruption of amino acid metabolism, which can cause a buildup of acids that are not usually present in the body. In GA1, this results in the buildup of glutaric acid, which can damage the brain.
The condition occurs due to a deficiency of an enzyme that helps break down certain amino acids. A lack of this enzyme results in the buildup of toxic compounds, such as glutaric acid, in the body.
Excessive levels of these toxic compounds can cause damage to the brain. In particular, they may damage the basal ganglia, the regions of the brain that help control movement.
Learn more about metabolic disorders in infants.
Within the first 3 years of life, a person with GA1 may experience an acute encephalopathic crisis. This can result in brain damage, movement problems, developmental delays, seizures, and bleeding in the brain and around the back of the eyes. Early clinical signs that may suggest acute encephalopathic crisis include:
- lack of appetite or difficulty feeding
- lack of energy
- muscle weakness
- nausea, vomiting, and diarrhea
In other cases, symptoms may begin in adolescence or adulthood. These may include nonspecific neurological symptoms such as headaches, vertigo, and reduced fine motor skills
People with GA1 may also experience metabolic crisis. This occurs when compounds, such as organic acids, build up to unusually high and dangerous levels. Stressors such as illness and fasting can trigger metabolic crises.
GA1 is the result of a change in the GCDH gene. This gene is responsible for producing the glutaryl-CoA dehydrogenase (GCDH) enzyme. When this enzyme is nonfunctional or deficient, the body cannot fully break down the amino acids lysine, hydroxylysine, and tryptophan.
Typically, the body breaks down these amino acids into glutaric acid and converts that acid into energy. However, in people with GA1, a deficiency in the GCDH enzyme results in a harmful buildup of glutaric acid in the brain and body.
GA1 is an autosomal recessive condition. This means that in order to inherit the condition, a person must receive two GCDH gene variations — one from each parent.
GA1 occurs in roughly 1 in 100,000 people in the overall population. However, it is more prevalent in certain groups, including:
- the Old Order Amish community in Pennsylvania
- the Oji-Cree First Nations in Canada
- the Irish Traveler community in Ireland
- the Lumbee population in North Carolina
- the Xhosa community in South Africa
Nearly all babies will have a simple blood test, known as a heel-prick test, to check for conditions that may not be immediately apparent. This screening method can help identify metabolic disorders such as GA1.
If the test shows unusual results, a metabolic team will conduct further testing to help confirm a diagnosis. A metabolic team may consist of a metabolic doctor, dietitian, and nurse specialist. Typically, a
To confirm a diagnosis, healthcare professionals may conduct GCDH enzyme analysis or
According to a 2020 study, early diagnosis and treatment of GA1 can prevent potential complications while supporting typical growth and psychomotor development.
The guidelines for managing and treating GA1 involve
A specialist metabolic dietitian will tailor a low protein diet. In particular, this diet will reduce the amounts of amino acids, such as lysine and tryptophan, that a person consumes. A dietitian may also provide lysine-free, tryptophan-reduced amino acid formulas to ensure adequate intake of essential amino acids, minerals, and vitamins.
The medical team will provide detailed instructions for emergency treatment. The emergency regimen varies slightly between children and adults but involves administering a solution rich in glucose or dextrose to provide energy and help limit the buildup of harmful substances in the brain and body.
Glutaric acidurias are a group of organic acidurias, which have three main types. Each type results from different genetic changes that affect different metabolic enzymes.
GA1 is the most common type. It occurs due to a change in the GCDH gene, which provides instructions for making the GCDH enzyme.
GA2 can occur due to changes in the ETFA, ETFB, or ETFDH gene. Variations in these genes can lead to a deficiency in two enzymes: electron transfer flavoprotein (ETF) and ETF-dehydrogenase (ETFDH).
The prevalence of GA3 is currently unknown. It may result from a variation in the C7ORF10 gene or the succinyl-CoA:glutarate-CoA transferase (SUGCT) gene.
GA1 is a rare inherited metabolic disorder. It results from a deficiency of the GCDH enzyme, which plays an important role in breaking down certain amino acids. Without this enzyme, toxic compounds such as glutaric acid may build up in the body.
In some cases, GA1 can cause brain injury and affect movement. Healthcare professionals often diagnose GA1 through blood and urine tests. Treatment for GA1 involves following a low protein diet and consuming special formulas to ensure sufficient nutritional intake.