Home > Newborn Disorders > Glutaric acidemia type 1
Glutaric acidemia type 1
Screening
Tested By
tandem mass spectrometry (MS/MS); sensitivity~90% [Nicola Longo, personal communication, 2007]; specificity=NA [American: 1996]Names
Glutaric acidemia type 1
Glutaric aciduria, type 1
GA1, GA-1, GA I
Glutaryl-CoA dehydrogenase deficiency
Overview
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 can then lead to brain injury, particularly in the basal ganglia.[Hedlund: 2006]Prevalence
About 1/40,000 Caucasian live births and 1/30,000 Swedish live births. [Glutaric acidemia type 1 info for professionals (STAR-G)] In Old Amish and Ojibway populations, the incidence may be as high as 1/300. [Nicola Longo, personal communication, 2007]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.
After 5 years of age, the risk of acute decompensation (acute dystonia) is low and children with normal neurological exam are likely to remain healthy. Treatment consists in the prompt therapy of fever, gastroenteritis or any condition causing catabolism with intravenous glucose and lipids and carnitine. Chronic therapy consists in a diet low in protein, lysine and tryptophan, and supplemented with carnitine.
Follow-up on positive screening test
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): Utah Newborn Screening Program, (801-584-8256); See also Services below;
- For evaluation and ongoing collaborative management, consult the following service(s): Medical Genetics, (801-231-3599); See also Services below;
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 info 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 and ongoing collaboration, particularly for dietary management. Genetic counseling for the family.Resources
Information & Support
For Professionals
ACT Sheet for Glutaric aciduria type 1 (ACMG)
(
346 KB)
Developed by the American College of Medical Genetics (ACMG), includes recommended responses to positive newborn screening
test results, diagnostic evaluation, clinical expectations, and sources of additional information. See the ACMG ACT Sheets
and Confirmatory Algorithms (link elsewhere on this page) for more info and sheets on other conditions.
ACT Sheets and Confirmatory Algorithms (ACMG)
The American College of Medical Genetics (ACMG) has developed ACTion (ACT) Sheets and algorithms for responding to positive
newborn screening test results. This page contains a table with links to all of the ACT Sheets and related algorithms.
Glutaric acidemia type 1 info for professionals (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, one of a series of Disorder Fact Sheets for Professionals;
structured list of information about the condition, with links to more information.
Resources for Glutaric acidemia type 1 (NLM)
Comprehensive compilation of links to information, articles, research, case studies, genetics, and more; from the National
Library of Medicine and the Genetic Alliance.
Glutaric acidemia type 1 (OMIM)
Extensive review of the literature, including clinical features and genetics, from the Online Mendelian Inheritance in Man
site, hosted by Johns Hopkins University, providing technical information for providers on genetic disorders, links to MEDLINE,
and links to other scientific information and sites.
For Parents and Patients
Glutaric acidemia type 1 info for parents (STAR-G)
From the Screening, Technology and Research in Genetics (STAR-G) program, providing information for parents about glutaric
acidemia and links to other sites including parent support groups.
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.
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 aimed at patients and families from the National Library of Medicine's Genetics Home Reference
site.
Services
Newborn Screening Programs
Utah Newborn Screening Program,
more info...
44 Mario Capecchi Drive
Salt Lake City, UT 84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening
Pediatric Medical Genetics
See all Pediatric Medical Genetics services providers (3) in our database.
For other services related to this condition, browse our Services categories or search our database.
Authors
| Reviewing Author: | Nicola Longo MD, PhD, 3/2011 |
| Compiled and edited by: | Alfred Romeo RN, PhD, 3/2007 |
| Content Last Updated: | 3/2008 |
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.