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Glutaric acidemia type II

Reviewed February 2014

What is glutaric acidemia type II?

Glutaric acidemia type II is an inherited disorder that interferes with the body's ability to break down proteins and fats to produce energy. Incompletely processed proteins and fats can build up in the body and cause the blood and tissues to become too acidic (metabolic acidosis).

Glutaric acidemia type II usually appears in infancy or early childhood as a sudden episode called a metabolic crisis, in which acidosis and low blood sugar (hypoglycemia) cause weakness, behavior changes such as poor feeding and decreased activity, and vomiting. These metabolic crises, which can be life-threatening, may be triggered by common childhood illnesses or other stresses.

In the most severe cases of glutaric acidemia type II, affected individuals may also be born with physical abnormalities. These may include brain malformations, an enlarged liver (hepatomegaly), a weakened and enlarged heart (dilated cardiomyopathy), fluid-filled cysts and other malformations of the kidneys, unusual facial features, and genital abnormalities. Glutaric acidemia type II may also cause a characteristic odor resembling that of sweaty feet.

Some affected individuals have less severe symptoms that begin later in childhood or in adulthood. In the mildest forms of glutaric acidemia type II, muscle weakness developing in adulthood may be the first sign of the disorder.

How common is glutaric acidemia type II?

Glutaric acidemia type II is a very rare disorder; its precise incidence is unknown. It has been reported in several different ethnic groups.

What genes are related to glutaric acidemia type II?

Mutations in any of three genes, ETFA, ETFB, and ETFDH, can result in glutaric acidemia type II. The ETFA and ETFB genes provide instructions for producing two protein segments, or subunits, that come together to make an enzyme called electron transfer flavoprotein. The ETFDH gene provides instructions for making another enzyme called electron transfer flavoprotein dehydrogenase.

Glutaric acidemia type II is caused by a deficiency in either of these two enzymes. Electron transfer flavoprotein and electron transfer flavoprotein dehydrogenase are normally active in the mitochondria, which are the energy-producing centers of cells. These enzymes help break down proteins and fats to provide energy for the body. When one of the enzymes is defective or missing, partially broken down nutrients accumulate in the cells and damage them, causing the signs and symptoms of glutaric acidemia type II.

People with mutations that result in a complete loss of either enzyme produced from the ETFA, ETFB or ETFDH genes are likely to experience the most severe symptoms of glutaric acidemia type II. Mutations that allow the enzyme to retain some activity may result in milder forms of the disorder.

Related Gene(s)

Changes in these genes are associated with glutaric acidemia type II.

  • ETFA
  • ETFB
  • ETFDH

How do people inherit glutaric acidemia type II?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Where can I find information about diagnosis or management of glutaric acidemia type II?

These resources address the diagnosis or management of glutaric acidemia type II and may include treatment providers.

  • Baby's First Test (http://www.babysfirsttest.org/newborn-screening/conditions/glutaric-acidemia-type-ii)
  • Genetic Testing Registry: Glutaric aciduria, type 2 (http://www.ncbi.nlm.nih.gov/gtr/conditions/C0268596)

You might also find information on the diagnosis or management of glutaric acidemia type II in Educational resources (/condition/glutaric-acidemia-type-ii/show/Educational+resources) and Patient support (/condition/glutaric-acidemia-type-ii/show/Patient+support).

General information about the diagnosis (http://ghr.nlm.nih.gov/handbook/consult/diagnosis) and management (http://ghr.nlm.nih.gov/handbook/consult/treatment) of genetic conditions is available in the Handbook. Read more about genetic testing (http://ghr.nlm.nih.gov/handbook/testing), particularly the difference between clinical tests and research tests (http://ghr.nlm.nih.gov/handbook/testing/researchtesting).

To locate a healthcare provider, see How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

Where can I find additional information about glutaric acidemia type II?

You may find the following resources about glutaric acidemia type II helpful. These materials are written for the general public.

You may also be interested in these resources, which are designed for healthcare professionals and researchers.

What other names do people use for glutaric acidemia type II?

  • electron transfer flavoprotein deficiency
  • EMA
  • ETFA deficiency
  • ETFB deficiency
  • ETFDH deficiency
  • ethylmalonic-adipicaciduria
  • GA II
  • glutaric acidemia, type 2
  • glutaric aciduria, type 2
  • MAD
  • MADD
  • multiple acyl-CoA dehydrogenase deficiency
  • multiple FAD dehydrogenase deficiency

For more information about naming genetic conditions, see the Genetics Home Reference Condition Naming Guidelines (http://ghr.nlm.nih.gov/ConditionNameGuide) and How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What if I still have specific questions about glutaric acidemia type II?

Ask the Genetic and Rare Diseases Information Center (http://rarediseases.info.nih.gov/gard).

What glossary definitions help with understanding glutaric acidemia type II?

acidosis ; aciduria ; autosomal ; autosomal recessive ; cardiomyopathy ; cell ; CoA ; coenzyme A ; cysts ; deficiency ; dehydrogenase ; dilated ; electron ; enzyme ; gene ; hypoglycemia ; incidence ; inherited ; mitochondria ; newborn screening ; oxidation ; protein ; recessive ; screening ; sign

You may find definitions for these and many other terms in the Genetics Home Reference Glossary (/glossary).

References

  • Angle B, Burton BK. Risk of sudden death and acute life-threatening events in patients with glutaric acidemia type II. Mol Genet Metab. 2008 Jan;93(1):36-9. Epub 2007 Oct 31. (http://www.ncbi.nlm.nih.gov/pubmed/17977044?dopt=Abstract)
  • Cornelius N, Frerman FE, Corydon TJ, Palmfeldt J, Bross P, Gregersen N, Olsen RK. Molecular mechanisms of riboflavin responsiveness in patients with ETF-QO variations and multiple acyl-CoA dehydrogenation deficiency. Hum Mol Genet. 2012 Aug 1;21(15):3435-48. doi: 10.1093/hmg/dds175. Epub 2012 May 18. (http://www.ncbi.nlm.nih.gov/pubmed/22611163?dopt=Abstract)
  • Curcoy A, Olsen RK, Ribes A, Trenchs V, Vilaseca MA, Campistol J, Osorio JH, Andresen BS, Gregersen N. Late-onset form of beta-electron transfer flavoprotein deficiency. Mol Genet Metab. 2003 Apr;78(4):247-9. (http://www.ncbi.nlm.nih.gov/pubmed/12706375?dopt=Abstract)
  • Goodman SI, Binard RJ, Woontner MR, Frerman FE. Glutaric acidemia type II: gene structure and mutations of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) gene. Mol Genet Metab. 2002 Sep-Oct;77(1-2):86-90. (http://www.ncbi.nlm.nih.gov/pubmed/12359134?dopt=Abstract)
  • OMIM: MULTIPLE ACYL-CoA DEHYDROGENASE DEFICIENCY (http://omim.org/entry/231680)
  • Olsen RK, Andresen BS, Christensen E, Bross P, Skovby F, Gregersen N. Clear relationship between ETF/ETFDH genotype and phenotype in patients with multiple acyl-CoA dehydrogenation deficiency. Hum Mutat. 2003 Jul;22(1):12-23. (http://www.ncbi.nlm.nih.gov/pubmed/12815589?dopt=Abstract)
  • Olsen RK, Olpin SE, Andresen BS, Miedzybrodzka ZH, Pourfarzam M, Merinero B, Frerman FE, Beresford MW, Dean JC, Cornelius N, Andersen O, Oldfors A, Holme E, Gregersen N, Turnbull DM, Morris AA. ETFDH mutations as a major cause of riboflavin-responsive multiple acyl-CoA dehydrogenation deficiency. Brain. 2007 Aug;130(Pt 8):2045-54. Epub 2007 Jun 20. (http://www.ncbi.nlm.nih.gov/pubmed/17584774?dopt=Abstract)
  • Olsen RK, Pourfarzam M, Morris AA, Dias RC, Knudsen I, Andresen BS, Gregersen N, Olpin SE. Lipid-storage myopathy and respiratory insufficiency due to ETFQO mutations in a patient with late-onset multiple acyl-CoA dehydrogenation deficiency. J Inherit Metab Dis. 2004;27(5):671-8. (http://www.ncbi.nlm.nih.gov/pubmed/15669683?dopt=Abstract)
  • Purevjav E, Kimura M, Takusa Y, Ohura T, Tsuchiya M, Hara N, Fukao T, Yamaguchi S. Molecular study of electron transfer flavoprotein alpha-subunit deficiency in two Japanese children with different phenotypes of glutaric acidemia type II. Eur J Clin Invest. 2002 Sep;32(9):707-12. (http://www.ncbi.nlm.nih.gov/pubmed/12486872?dopt=Abstract)
  • Schiff M, Froissart R, Olsen RK, Acquaviva C, Vianey-Saban C. Electron transfer flavoprotein deficiency: functional and molecular aspects. Mol Genet Metab. 2006 Jun;88(2):153-8. Epub 2006 Feb 28. (http://www.ncbi.nlm.nih.gov/pubmed/16510302?dopt=Abstract)
  • Takken T, Custers J, Visser G, Dorland L, Helders P, de Koning T. Prolonged exercise testing in two children with a mild Multiple Acyl-CoA-Dehydrogenase deficiency. Nutr Metab (Lond). 2005 May 20;2(1):12. (http://www.ncbi.nlm.nih.gov/pubmed/15907213?dopt=Abstract)

 

The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.

 
Reviewed: February 2014
Published: May 18, 2015