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Screening & Prevention >> Newborn Screening >> Fatty Acid Oxidation Disorders >> Glutaric acidemia type 2

Glutaric acidemia type 2

Disorder Category

a fatty acid oxidation disorder

Screening

Finding

elevated C4 and C5

Tested By

tandem mass spectrometry (MS/MS); sensitivity=100%; specificity=100% [Schulze: 2003]

Names

Glutaric acidemia type 2

Glutaric acidemia II (GA2, GA II)

Glutaric aciduria type 2

Multiple acyl-CoA dehydrogenase deficiency (MAD, MADD)

Electron transfer flavoprotein dehydrogenase deficiency (ETFA, ETFB, ETFDH)

ICD-9

277.85, Disorders of fatty acid oxidation

Overview

Due to a deficiency of one of three electron transfer flavoprotien enzymes (ETFA, ETFB, or ETFDH), patients are unable to produce energy from fats and proteins resulting in hypoglycemia, weakness, and usually infant death. Three forms of the condition exist - neonatal onset with congenital anomalies, neonatal onset without anomalies, and a late-onset or mild form that may be amenable to treatement. The differences relate to the amount of residual enzyme activity.

Prevalence

about 1/250,000 live births [Schulze: 2003]

Inheritance

autosomal recessive

Maternal and Family History

Death may appear to be from Sudden Infant Death Syndrome (SIDS).

Prenatal Testing

Amniocentisis for analyte analysis or enzyme analysis.

Clinical Characteristics

With treatment, possible only in the late-onset form, some of the neurologic sequelae and the carnitine deficiency may be avoided. Death within the first few weeks is almost invariable in those with the neonatal or congenital anomaly form. Without treatment, severity of symptoms and age of presentation in the late-onset form is quite variable.

Initial signs and symptoms may include: In the neonatal with anomalies form:
  • facial dysmorphism - high forehead, depressed nasal bridge, low-set abnormally formed ears;
  • rocker bottom feet;
  • muscular defects of the abdominal wall;
  • renal anomalies;
  • anomalies of the external genitalia; and
  • vitually all will die within a week of birth.


In the neonatal without anomalies form, illness generally presents within the first few days, including:
  • hypotonia,
  • tachypnea,
  • metabolic acidosis,
  • hepatomegaly,
  • sweaty feet odor,
  • lab findings:
    • metabolic acidosis, and
    • hypoglycemia.


Those with mild or late-onset form may present with:
  • failure to thrive,
  • hepatomegaly,
  • hypoglycemia
  • hepatic dysfunction,
  • exercise-induced muscle pain, and
  • movement disorder.

Follow-up on positive screening test

Quantitative plasma acylcarnitine profile, urine organic acid and acylglycine analysis, confirmation with ETF/ETF-QO enzyme assay and gene sequencing.

Primary care management

Upon notification of the + screen

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 2 info for parents, STAR-G for additional information);
  • Support implementation and maintenance of low fat, low proteindiet;
  • Oral L-carnitine, riboflavin, or glycine supplements may be indicated;
  • For those identified after irreversible consequences, assist in management, particularly with developmental and educational interventions.

Specialty Care Management

Initial consultation and ongoing collaboration if the child is affected. A dietician may work with the family to devise an optimal approach to dietary management.

Resources

Links

For Professionals

Glutaric acidemia type 2 info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

Glutaric acidemia type 2, late onset, info for professionals, STAR-G
On the Screening, Technology and Research in Genetics (STAR-G) site, one of a series of Disorder Fact Sheets for Professionals; structured list of information about the condition, with links to more information.

ACT Sheet for Glutaric acidemia type 2 from ACMG (pdf 131kb)
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.

ACMG ACT Sheets and Confirmatory Algorithms
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 2, OMIM
Extensive review of the literature, including clinical features and gene therapy, 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.

Utah Newborn Screening Program
The site provides information and statistics about the program and related legislation, training for practices, and the conditions screened for.

For Parents

Glutaric acidemia type 2 info for parents, STAR-G
From the Screening, Technology and Research in Genetics (STAR-G) site, providing information for parents about glutaric acidemia 2 and links to other sites including parent support groups.

Glutaric acidemia type 2, Genetics Home Reference
Excellent, detailed review aimed at patients and families from the National Library of Medicine's Genetics Home Reference site.

Fatty Oxidation Disorders (FOD) Family Support Group
The FODsupport.org site offers a variety of information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.

Services

Newborn Screening Programs

Utah Newborn Screening Program, more info...
44 Mario Capecchi Drive
Salt Lake City, UT84114
Phone: 801-584-8256
Fax: 801-536-0966
http://health.utah.gov/newbornscreening

Pediatric Genetics

Metabolic Clinic, more info...
100 Mario Capecchi Drive
Salt Lake City, UT84113
Phone: 801-585-2457
Fax: 585-7252
http://www.ped.med.utah.edu/divisions/divisions.htm

See all Pediatric Genetics services providers (3) in our database.

For other services related to this condition, browse our Services categories or search our database.

Helpful Articles

PubMed search for articles on glutaric acidemia type 2 in the last 5 years.

Authors

Reviewing Author: Nicola Longo MD, PhD, 3/2007
Compiled and edited by: Alfred Romeo RN, PhD, 3/2007
Content Last Updated: 3/2008

Page Bibliography

Schulze A, Lindner M, Kohlmuller D, Olgemoller K, Mayatepek E, Hoffmann GF.
Expanded newborn screening for inborn errors of metabolism by electrospray ionization-tandem mass spectrometry: results, outcome, and implications.
Pediatrics. 2003;111(6 Pt 1):1399-406. PubMed abstract
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