1. Home
  2. Physicians & Professionals
  3. Newborn Screening
  4. Glutaric Acidemia Type 1

Glutaric Acidemia Type 1

On this Page
Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

GA1, GA-1, GA I
GCDH deficiency
Glutaric aciduria, type 1
Glutaryl-CoA dehydrogenase deficiency

ICD-10 Coding

E72.3, Disorders of lysine and hydroxylysine metabolism

Disorder Category

Organic acidemia

Screening

Abnormal Finding

Elevated C5-DC (glutaryl) carnitine

Tested By

Tandem mass spectrometry (MS/MS); sensitivity ~96%; specificity=NA [Boy: 2018]

Description

In glutaric acidemia type 1 (GA1), defective activity of glutaryl-CoA dehydrogenase, an enzyme necessary for the break-down of lysine, hydroxylysine, and tryptophan, causes an accumulation of glutaric and 3-OH-glutaric acid, which are intermediates in the amino acid catabolism. These toxic metabolites can result in acute encephalopathic crisis that usually presents within the first 6 years of life. Crises result in striatal injury and subsequently lead to complex movement disorders. [Larson: 2019] Mutations in the GCDH gene cause GA1.

Clinical Characteristics

With early diagnosis and full adherence to treatment, 80-90% of individuals with GA1 will remain largely asymptomatic. [Viau: 2012] [Boy: 2018]
Without treatment, a majority of individuals with early-onset GA1 will experience an encephalopathic crisis, usually occurring within the first year of life. [Kölker: 2006] [Boy: 2017]
Symptoms are usually triggered by illness (high fever, vomiting, dehydration); crises may also be triggered by vaccinations and surgery. Children may be healthy until the first metabolic crisis. Profuse sweating may occur in some affected children. Acute decompensation has not been reported after 6 years of age, although some undiagnosed patients have presented with a leukoencephalopathy after this age. [Kölker: 2006]
Initial symptoms/signs may include:
  • Macrocephaly
  • Failure to thrive
  • Metabolic ketoacidosis
  • Hypotonia
  • Dystonia and athetosis
After 6 years of age, the risk of acute decompensation (acute dystonia) appears to decrease, and children with a normal neurological exam and brain MRI are likely to remain healthy. Treatment consists of aggressive emergency management, provision of calories through intravenous glucose and lipids, and carnitine to aid in removal of toxic metabolites. Chronic therapy consists of avoidance of catabolism, a diet low in lysine and tryptophan, and carnitine supplementation.

Incidence

The incidence is approximately 1:90,000 in the United States. [Therrell: 2014] Certain geographic regions have a higher incidence due to a founder effect. These regions include Ojibway-Cree First Nation Canadians of Manitoba and Ontario, South African Xhosa people, Pennsylvania Amish, Lumbee Native Americans of North Carolina, and Irish Traveler communities in the Republic of Ireland. [Larson: 2019]

Inheritance

Autosomal recessive

Primary Care Management

Next Steps After a Positive Screen

  • Contact the family immediately and evaluate the infant for macrocephaly, hypotonia, and/or signs of decompensation.

Confirming the Diagnosis

  • To confirm the diagnosis, work with Newborn Screening Services (see UT providers [3]).
  • Follow-up testing will include quantitative plasma acylcarnitine profile, urine organic acid and acylglycine analysis, confirmation with gene sequencing. If negative, consider riboflavin transporter deficiency if biochemical abnormalities (plasma acylcarnitine profile) are persistent.

If the Diagnosis is Confirmed

  • For evaluation and ongoing collaborative management, consult Medical Genetics (see UT providers [8]).
  • 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 a 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.

Resources

Information & Support

After a Diagnosis or Problem is Identified
Families can face a big change when their baby tests positive for a newborn condition. Find information about A New Diagnosis - You Are Not Alone; Caring for Children with Special Health Care Needs; Assistance in Choosing Providers; Partnering with Healthcare Providers; Top Ten Things to Do After a Diagnosis.

For Professionals

Glutaric Acidemia Type 1 (OMIM)
Information about clinical features, diagnosis, management, and molecular and population genetics; Online Mendelian Inheritance in Man, authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine

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.

Glutaric Acidemia Type 1 (MedlinePlus)
Information for families that includes description, frequency, causes, inheritance, other names, and additional resources; from the National Library of Medicine.

Tools

UT ACT Sheet for Glutaric Acidemia Type I (ACMG) (PDF Document 136 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive, along with resources for consultation and patient education/support; from the American College of Genetics and Genomics

Confirmatory Algorithms for Glutaric Acidemia Type 1 (ACMG) (PDF Document 178 KB)
An algorithm of the basic steps involved in determining the final diagnosis of an infant with a positive newborn screen; American College of Medical Genetics.

Services for Patients & Families in Utah (UT)

For services not listed above, browse our Services categories or search our database.

* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.

Helpful Articles

PubMed search for glutaric acidemia type 1 and neonatal screening, last 5 years.

Authors & Reviewers

Initial publication: December 2007; last update/revision: March 2020
Current Authors and Reviewers:
Author: Chelsea Norman, BS, RDN, CD
Reviewer: Nicola Longo, MD, Ph.D.
Authoring history
2012: update: Kimberly Hart, MS, LCGCA
2011: update: Nicola Longo, MD, Ph.D.A
2007: first version: Chuck Norlin, MDA
AAuthor; CAContributing Author; SASenior Author; RReviewer

Page Bibliography

Boy N, Mengler K, Thimm E, Schiergens KA, Marquardt T, Weinhold N, Marquardt I, Das AM, Freisinger P, Grünert SC, Vossbeck J, Steinfeld R, Baumgartner MR, Beblo S, Dieckmann A, Näke A, Lindner M, Heringer J, Hoffmann GF, Mühlhausen C, Maier EM, Ensenauer R, Garbade SF, Kölker S.
Newborn screening: A disease-changing intervention for glutaric aciduria type 1.
Ann Neurol. 2018;83(5):970-979. PubMed abstract

Boy N, Mühlhausen C, Maier EM, Heringer J, Assmann B, Burgard P, Dixon M, Fleissner S, Greenberg CR, Harting I, Hoffmann GF, Karall D, Koeller DM, Krawinkel MB, Okun JG, Opladen T, Posset R, Sahm K, Zschocke J, Kölker S.
Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision.
J Inherit Metab Dis. 2017;40(1):75-101. PubMed abstract

Kölker S, Garbade SF, Greenberg CR, Leonard JV, Saudubray JM, Ribes A, Kalkanoglu HS, Lund AM, Merinero B, Wajner M, Troncoso M, Williams M, Walter JH, Campistol J, Martí-Herrero M, Caswill M, Burlina AB, Lagler F, Maier EM, Schwahn B, Tokatli A, Dursun A, Coskun T, Chalmers RA, Koeller DM, Zschocke J, Christensen E, Burgard P, Hoffmann GF.
Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency.
Pediatr Res. 2006;59(6):840-7. PubMed abstract

Larson A, Goodman S.
Glutaric Acidemia Type 1.
GeneReviews. 2019. PubMed abstract

Therrell BL Jr, Lloyd-Puryear MA, Camp KM, Mann MY.
Inborn errors of metabolism identified via newborn screening: Ten-year incidence data and costs of nutritional interventions for research agenda planning.
Mol Genet Metab. 2014;113(1-2):14-26. PubMed abstract / Full Text

Viau K, Ernst SL, Vanzo RJ, Botto LD, Pasquali M, Longo N.
Glutaric acidemia type 1: outcomes before and after expanded newborn screening.
Mol Genet Metab. 2012;106(4):430-8. PubMed abstract