Glutaric Acidemia Type 1
Screening
Tested By
Tandem mass spectrometry (MS/MS); sensitivity~90% [Nicola Longo, personal communication, 2007]; specificity=NA [American: 1996]Overview
In glutaric acidemia type 1 (GA1), inadequate quantities of glutaryl-CoA dehydrogenase limit the ability to break down lysine, hydroxylysine, and tryptophan, leading to excessive levels of their intermediate metabolic products (glutaric and 3-OH-glutaric acid). These and other chemicals can then lead to brain injury, particularly in the basal ganglia.[Hedlund: 2006] Mutations in the GCDH gene cause GA1.Incidence
Prevalence is about 1:40,000 Caucasian live births and 1:30,000 Swedish live births; n Old Amish and Ojibway populations, the incidence may be as high as 1:300. (Glutaric Acidemia Type 1 - Information for Professionals (STAR-G))Prenatal Testing
DNA testing is possible by amniocentesis if both disease causing mutations of an affected family member have been identified.Clinical Characteristics
With treatment, normal outcome is possible. Without treatment, outcomes vary but many will have encephalitis-like crises that may result in developmental delay, neurologic deterioration, and spastic/dystonic cerebral palsy. Otherwise healthy newborns may have macrocephaly sometimes with hypotonia. Acute decompensation usually occurs between 6 and 18 months of age. Symptoms are usually triggered by illness (high fever, vomiting, dehydration). Children may be healthy until the first metabolic crisis. Profuse sweating may occur in some affected children. Acute decompensation has not been reported after 5 years of age, although some undiagnosed patients have presented with a leukoencephalopathy after this age.Initial symptoms/signs may include:
- Macrocephaly
- Failure to thrive
- Metabolic ketoacidosis
- Hypotonia
- Dystonia and athetosis.
Follow-up Testing after Positive Screen
Quantitative plasma acylcarnitine profile, urine organic acid and acylglycine analysis, confirmation with ETF/ETF-QO enzyme assay and/or gene sequencing. If negative, consider riboflavin transporter deficiency if biochemical abnormalities (plasma acylcarnitine profile) are persistent.Primary Care Management
Upon Notification of the + Screen
- Contact the family immediately and evaluate the infant macrocephaly and hypotonia.
- To confirm the diagnosis, work with the following service(s): see all Newborn Screening Programs services providers (3) in our database.
- For evaluation and ongoing collaborative management, consult the following service(s): see all Pediatric Genetics services providers (3) in our database.
If the Diagnosis is Confirmed
- Educate the family regarding signs, symptoms, and the need for urgent care when the infant becomes ill (see Glutaric Acidemia Type 1 - Information for Parents (STAR-G) for additional information).
- Support initiation and maintenance of low lysine, low tryptophan diet.
- Glucose, intralipids, carnitine, and fluids given intravenously may be indicated during episodes of acute, intercurrent illness.
- For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.
Specialty Care Collaboration
Initial consultation with the following service(s):see all Pediatric Genetics services providers (3) in our database; and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
Glutaric Acidemia Type 1 (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University.
Genetics in Primary Care Institute (AAP)
The goal of this site is to increase collaboration in the care of children with known or suspected genetic disorders. It includes
health supervision guidelines and other useful resources; represents a collaboration among the Health Resources & Services
Administration, the Maternal and Child Health Bureau, and the American Academy of Pediatrics.
For Parents and Patients
Glutaric Acidemia Type 1 - Information for Parents (STAR-G)
A fact sheet, written by a genetic counselor and reviewed by metabolic and genetic specialists, for families who have received
an initial diagnosis of this newborn disorder; Screening, Technology and Research in Genetics.
Organic Acidemia Association (OAA)
A volunteer non-profit organization whose mission is to empower families and health care professionals with knowledge in organic
acidemia metabolic disorders.
Resources for Glutaric Acidemia Type 1 (Disease InfoSearch)
Compilation of information, articles, research, case studies, and genetics links; from Genetic Alliance.
The International Organization of Glutaric Acidemia
A non-profit organization, provides information for parents and the public; newsletters; event information; a message board
area; and links to other sites.
Glutaric Acidemia Type 1 (Genetics Home Reference)
Excellent, detailed review of condition for patients and families; sponsored by the U.S. National Library of Medicine.
Tools
ACT Sheet for Glutaric Aciduria Type 1 (ACMG) (
346 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical
Genetics.
Services
Newborn Screening Programs
See all Newborn Screening Programs services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Page Bibliography
American Academy of Pediatrics.
Newborn screening fact sheets. American Academy of Pediatrics. Committee on Genetics.
Pediatrics.
1996;98(3 Pt 1):473-501.
PubMed abstract
Hedlund GL, Longo N, Pasquali M.
Glutaric acidemia type 1.
Am J Med Genet C Semin Med Genet.
2006;142C(2):86-94.
PubMed abstract / Full Text
Glutaric acidemias (GA) comprise different disorders resulting in an increased urinary excretion of glutaric acid. Early
diagnosis and therapy reduce the risk of acute dystonia in patients with GA-1.