GA-I is inherited in an autosomal recessive pattern. Normally a person has two functional GCDH genes. In people with GA-I, both genes have a mutation and there is a deficiency of the critical enzyme activity. Each parent of a newborn with GA-I typically has one functional and one mutated gene and is considered a carrier. When both parents are carriers, the chance of a newborn inheriting two mutated genes is 25%.
Carriers of GA-I do not typically have symptoms.
Newborns with GA-I may not have obvious symptoms at birth, aside from large head size (macrocephaly). Untreated, symptoms may include poor growth and episodes of dystonia and athetosis (unusual movements of the limbs), rigidness and spasticity. The episodes are usually triggered by an illness.
- Incidence: Published estimates for the incidence of GA-I range from 1 in 30,000 to 1 in more than 250,000. In New York, the incidence has been closer to 1 in 250,000. GA-I is more common in Amish and Ojibwa populations.
- New York State Method of Screening (First Tier): Screening for GA-I is accomplished by measuring the acylcarnitine C5DC by tandem mass spectrometry (MS/MS).
- Second Tier Screening: None
- Testing can be affected by: There have been reports of a positive newborn screen for GA-I due to the mother having the disorder.
- Interpretation/reporting of data: Results are reported as screen negative, borderline or as a referral. A repeat specimen should be collected for a borderline result. Prompt consultation with a specialist is required for a referral.
- Referral to Specialty Care Center: Patients with an abnormal newborn screen for GA-I are referred to an Inherited Metabolic Disorder Specialty Care Center for evaluation by a biochemical geneticist trained in the diagnosis and treatment of GA-I.
Diagnostic testing may include urine organic acid analysis, enzyme analysis and genetic testing of the GCDH gene.
Treatment is typically dietary management, including a diet low in lysine and tryptophan. Supplementation with carnitine may also be indicated. Additional medical care may be required during times of illness.
Outcome is variable, and dependent on multiple factors, including the severity of disease and response to treatments.
Glutaric acidemia, type I (GA-I) is a disorder of organic acid metabolism (inherited metabolic disorder).
GA-I is caused by mutations in the GCDH gene. Components of protein (the amino acids lysine, hydroxylysine, and tryptophan) are broken down as part of normal metabolism. Mutations in the GCDH gene cause a deficiency of an important enzyme, glutaryl-CoA dehydrogenase. Without this enzyme, the amino acids are not broken down, accumulate in the brain and cause neurologic symptoms.