Glutaric acidemia type 2

Other Names

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)

Diagnosis Coding

277.85, Disorders of fatty acid oxidation

Disorder Category

A fatty acid oxidation disorder



Elevated C4 and C5

Tested By

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


Glutaric acidemia type 2 is caused by a deficiency of one of three electron transfer flavoprotein enzymes (ETFA, ETFB, or ETFDH). Patients are unable to produce energy from fats and proteins resulting in hypoglycemia, weakness, and in severe cases 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 treatment. More recently, a form due to defective transport of riboflavin (the cofactor of the ETF complex) has been reported (Brown-Vialetto-Van Laere and Fazio Londe syndrome) [Bosch: 2011]. The differences in clinical presentation relate to the amount of residual enzyme activity.


About 1 in 250,000 live births [Schulze: 2003]


Autosomal recessive

Maternal & Family History

Sudden Infant Death Syndrome (SIDS) in siblings is possible.

Prenatal Testing

Amniocentesis for DNA analysis.

Clinical Characteristics

With treatment, possible only in the milder forms, 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, patients with the neonatal variety will die during an acute attack. Patients with the late-onset form will experience exercise intolerance.

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
  • virtually all patients with congenital anomalies 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
    • hypoglycemia

Those with mild or late-onset form may present with:
  • exercise-induced muscle pain
  • movement disorder

Treatment consists of fasting avoidance, carnitine and riboflavin supplements.

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

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 - Information 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 Collaboration

Initial consultation with the following service(s): Pediatric Medical Genetics , (801-213-3599); See also Services below; 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.


Information & Support

For Professionals

Glutaric Acidemia Type 2 - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

Glutaric Acidemia Type 2 - Information for Professionals (STAR-G)
Structured list of information about the condition and links to more information; Screening, Technology, and Research in Genetics.

ACT Sheet for Glutaric Acidemia Type 2 (C4 & C5) (ACMG) (PDF Document 347 KB)
Contains short-term recommendations for clinical follow-up of the newborn who has screened positive; American College of Medical Genetics.

Newborn Screening ACT Sheets & Confirmatory Algorithms (ACMG)
ACTion (ACT) Sheets and algorithms for responding to positive newborn screening test results, membership required; American College of Medical Genetics.

Resources for Glutaric acidemia type 2 (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 2 (OMIM)
Extensive review of literature that provides technical information on genetic disorders; Online Mendelian Inheritance in Man site, hosted by Johns Hopkins University.

Utah Newborn Screening Program (UDOH)
Provides information about the program, related legislation, training for practices, and newborn conditions; Utah Department of Health.

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. Includes health supervision guidelines and other useful resources; 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 2 - 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 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
Information for families about fatty acid oxidation disorders, support groups, coping, finances, and links to other sites.


Genetics-related clinical services throughout the world can be found through Genetics Clinic Directory (GeneTests).

Newborn Screening Programs

See all Newborn Screening Programs services providers (3) in our database.

Pediatric Genetics

See all Pediatric Genetics services providers (5) in our database.

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


Reviewing Authors: Kimberly Hart, MS, LCGC - 7/2012
Nicola Longo, MD, PhD - 3/2011
Compiled and edited by: Alfred Romeo, RN, PhD - 3/2007
Content Last Updated: 7/2012

Page Bibliography

Bosch AM, Abeling NG, Ijlst L, Knoester H, van der Pol WL, Stroomer AE, Wanders RJ, Visser G, Wijburg FA, Duran M, Waterham HR.
Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment.
J Inherit Metab Dis. 2011;34(1):159-64. PubMed abstract / Full Text
High dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome, as well as for the Fazio Londe syndrome, which is considered to be the same disease entity without the deafness.

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