Glutaricaciduria II

Glutaricaciduria II

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Glutaricaciduria II is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • GA II
  • Glutaric Acidemia II
  • Glutaric Aciduria II
  • Glutaricacidemia II
  • Multiple Acyl-Co-A Dehydrogenation Deficiency
  • MADD
  • Electron Transfer Flavoprotein: Ubiquinone Oxidoreductase, Deficiency of
  • Electron Transfer Flavoprotein, Deficiency of

Disorder Subdivisions

  • None

General Discussion

Glutaricaciduria II is one of the conditions termed organic acidemias. Individuals with these conditions have a deficiency or absence of an enzyme that prevents them from breaking down certain chenicals in the body, resulting the accumulation of several organic acids in the blood and urine. Two enzymes that may be deficient in glutaricaciduria II are electron transfer flavoprotein (ETF) and ETF-ubiquinone oxidoreductase (ETF:QO). A complete enzyme deficiency causes a severe form of the disorder termed neonatal glutaricaciduria ll that is associated with a short life span and, sometimes, with specific physical birth defects. The less severe form of the disorder is termed late onset glutaricaciduria ll and has an extremely variable age of onset. Symptoms include nausea, vomiting, weakness and low blood sugar (hypoglycemia). Glutaricaciduria II is inherited as an autosomal recessive genetic disorder.

Symptoms

Newborns with the neonatal form of the disorder may have severe hypoglycemia, respiratory distress, low muscle tone, an odor of sweaty feet, liver abnormalities (hepatomegaly) and kidney abnormalities. Physical abnormalities are sometimes present and can include a large head (macrocephaly), high forehead, flat nasal bridge, malformed ears and genital abnormalities.



Symptoms of the late onset form of the disorder are variable and may include hypoglycemia and intermittent periods of vomiting and weakness.

Causes

Glutaricaciduria ll is caused by a deficiency or absence of enzymes that break down fats and proteins in the body, resulting in the accumulation of several organic acids in the blood and urine. Two enzymes that have been associated with glutaricaciduria II are electron transfer flavoprotein (ETF) and EFT-ubiquinone oxidoreductase (ETF:QO). Some individuals with glutaricaciduria ll have normal levels of these enzymes and the abnormal enzyme in those patients is not known.



Glutaricaciduria ll is inherited as an autosomal recessive genetic trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.



Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.

Affected Populations

No reliable data exist on the incidence of this condition.

Standard Therapies

Diagnosis

The diagnosis of glutaricaciduria ll is usually made by examining urine organic acids. The characteristic pattern for glutaricaciduria is an elevation of glutaric, ethylmalonic, adipic and isovaleric acid. Some individuals with this condition are initially identified through newborn blood screening using tandem mass spectrometry for the markers C4, C5, C6, C8 and C10. Some individuals do not have an abnormal pattern of urine organic acids except when they are ill. The definitive diagnosis of glutaricaciduria ll is made by demonstrating abnormalities in ETF or ETF-QO antigens or activity in cultured fibroblast cells obtained from a skin biopsy. Prenatal diagnosis may be possible by measuring glutaric acid in amniotic fluid.



Treatment

Glutaricaciduria is usually treated with a high carbohydrate, low protein and low fat diet. It is recommended that affected individuals eat often to avoid low blood sugar. Dietary supplementation with riboflavin, glycine and carnitine may be helpful.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.



For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:



Tollfree: (800) 411-1222

TTY: (866) 411-1010

Email: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

References

JOURNAL ARTICLES

Brusilow SW, Vallee DL. Symptomatic inborn errors of metabolism in the neonate. Current Therapy in Neonatal-Perinatal Medicine. Marcel Decker. 1985;24-27.



FROM THE INTERNET

McKusick VA. Online Mendelian Inheritance in Man, 6th ed. Johns Hopkins University Press; 1983:703,735,1038.

Resources

CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174

Email: enquiries@climb.org.uk

Internet: http://www.CLIMB.org.uk



Lactic Acidosis Support Trust

1A Whitley Close

Middlewich

Cheshire, CW10 0NQ

United Kingdom

Tel: 0160683719

Fax: 01606837198



Organic Acidemia Association

P.O. Box 1008

Pinole, CA 94564

USA

Tel: (763)559-1797

Fax: (763)694-0017

Email: carolbarton@oaanews.org

Internet: http://www.oaanews.org/index.htm



Organic Acidaemias UK

5, Saxon Road

Ashford

Middlesex, TW15 1QL

United Kingdom

Tel: 4401784245989

Email: info.oauk@gmail.com

Internet: http://myweb.tiscali.co.uk/priddy/



FOD (Fatty Oxidation Disorders) Family Support Group

PO Box 54

Okemos, MI 48864

USA

Tel: (517)381-1940

Fax: (866)290-5206

Email: deb@fodsupport.org

Internet: http://www.fodsupport.org



Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223

Internet: http://rarediseases.info.nih.gov/GARD/



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into myCigna.com. For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see http://www.rarediseases.org/search/rdblist.html.

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