Acidemia Isovaleric

Acidemia Isovaleric

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Acidemia Isovaleric 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

  • Isovaleric Acid CoA Dehydrogenase Deficiency
  • Isovaleric Acidaemia
  • Isovalericacidemia
  • Isovaleryl CoA Carboxylase Deficiency
  • IVA

Disorder Subdivisions

  • None

General Discussion

Isovaleric Acidemia is a hereditary metabolic disorder. It is characterized by a deficiency of the enzyme isovaleryl CoA dehydrogenase. The disorder occurs in both an acute and a chronic intermittent form. In the acute form of Isovaleric Acidemia, vomiting, refusal to eat, and listlessness usually occur. With treatment and low protein diet, the disorder becomes chronically intermittent, and a nearly normal life is possible.

Symptoms

Isovaleric Acidemia is a rare metabolic disorder that occurs in an acute and a chronic intermittent form. The disorder may start any time between the first week of life and adolescence. It is characterized by attacks of vomiting, lack of appetite and listlessness. Infants with Isovaleric Acidemia become increasingly listless, and they sometimes shake or tremble. They often have a lower than normal body temperature (hypothermia). In most cases, a strong odor like that of "sweaty feet" occurs. Intermittent episodes are usually triggered by upper respiratory infections or excessive eating of high protein foods. Severe acidity and the presence of ketone bodies in blood and body tissues (ketoacidosis) usually follows and patients may lapse into a coma.



Ketoacidotic episodes tend to occur frequently in early infancy and young childhood, but their frequency usually diminishes as the patient grows older. Children with Isovaleric Acidemia often show a natural aversion to protein foods, even at a young age.

Causes

Isovaleric Acidemia is a genetic disorder inherited through autosomal recessive genes. Symptoms are the result of a deficiency of the enzyme isovaleric co-enzyme A (CoA) dehydrogenase, which is needed for the breakdown of the amino acid leucine. Human traits, including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective 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 generally will not show symptoms of the disorder. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. On average, fifty percent of their children will be carriers of the disease, while 25 percent will receive a normal copy of the gene from each parent for that trait. The risks are the same for each pregnancy.

Affected Populations

Isovaleric Acidemia is a rare disorder affecting males and females in equal numbers, usually beginning during infancy.

Standard Therapies

Diagnosis

In some cases, Isovaleric Acidemia may be diagnosed before birth (prenatally) by measuring the concentration of abnormal metabolites in amniotic fluid or the activity of the isovaleryl-CoA dehydrogenase enzyme in fluid or tissue samples obtained from the fetus or uterus during pregnancy (amniocentesis or chorionic villus sampling [CVS]. During amniocentesis, a sample of fluid surrounding the developing fetus is removed and analyzed. CVS involves the removal and examination of tissue from a portion of the placenta. The disorder can be identified at birth through expanded newborn screening with tandem mass spectrometry.



In most affected infants, the disorder is diagnosed or confirmed in the first weeks of life, based upon a thorough clinical evaluation, a detailed patient and family history, and a variety of specialized tests. Laboratory studies (assays) are typically conducted on certain white blood cells (leukocytes) or cultured skin cells (fibroblasts) to confirm deficient activity of the isovaleryl-CoA dehydrogenase enzyme. Additional laboratory studies may reveal excessive levels of acids and increased accumulations of ketone bodies in bodily tissues and fluids (ketoacidosis); increased levels of glycine in the blood and urine (hyperglycinemia and hyperglycinuria); high levels of ammonia in the blood (hyperammonemia); and/or decreased levels of circulating platelets and white blood cells (thrombocytopenia and neutropenia).



Treatment

The disorder is treated by a diet with moderate restriction of the amino acid leucine and supplementation of L-carnitine. Administration of glycine at 150-300 mg/day is life-saving and may permit normal growth and development. Other treatment is symptomatic and supportive. Genetic counseling is recommended for families of children with Isovaleric Acidemia.

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

TEXTBOOKS

Sweetman L, Williams JD. Branched chain organic acidurias in The Metabolic and Molecular Basis of Inherited Disease. Scriver C, Beaudet AL, Sly W, Valle D, eds. (McGraw-Hill, New York, 2001), pp. 2125-64.



Mohsen A-W, Vockley J. Biochemical characteristics of recombinant human isovaleryl-CoA dehydrogenase pre-treated with ethylenediaminetetraacetate in Flabins and Flavoproteins. Rudolf Weber, New York, 1999: 515-18.



JOURNAL ARTICLES

Vockley J, Rogan PK, Anderson BD, et al. Exon skipping in IVD RNA processing in isovaleric academia caused by point mutations in the coding region of the IVD gene. Am J Hum Genet. 2000;66:356-67.



Mohsen AW, Anderson BD, Volchenboum SL, et al. Characterization of molecular defects in isovaleryl-CoA dehydrogenase in patients with isovaleric academia. Biochemistry. 1998;37:10325-35.



Vockley J, Parimoo B, Tanaka K. Molecular characterization of four different classes of mutations in the isovaleryl-CoA dehydrogenase gene responsible for isovaleric academia. Am J Hum Genet. 1991;40:147-57.



de Sousa C, Chalmers RA, Stacey TE, Tracey BM, Weaver CM, Bradley D.. The response to L-carnitine and glycine therapy in isovaleric acidaemia. Eur J Ped. 1986;144:451-56.



Hine DG, Hack AM, Goodman SI, Tanaka K. Stable isotope dilution analysis of isovalerylglycine in amniotic fluid and urine and its application for the prenatal diagnosis of isovaleric academia. Pediatr Res. 1986;20:222-26.



Hine DG, Tanaka K. The identification and the excretion pattern of isovaleryl glucuronide in the urine of patients with isovaleric academia. Pediatr Res. 1984;18:508-12.



Budd MA, Tanaka K, Holmes LB, Efron ML, Crawford JD, Isselbacher KJ. Isovaleric academia: clinical features of a new genetic defect of leucine metabolism. N Engl J Med. 1967;277:321-27.



FROM THE INTERNET

McKusick VA, ed. Online Mendelian Inehritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 243500; Last Update: 4/10/2000.

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



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553

Email: info@thearc.org

Internet: http://www.thearc.org



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/



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583

Email: NDDIC@info.niddk.nih.gov

Internet: http://www2.niddk.nih.gov/



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/



Madisons Foundation

PO Box 241956

Los Angeles, CA 90024

Tel: (310)264-0826

Fax: (310)264-4766

Email: getinfo@madisonsfoundation.org

Internet: http://www.madisonsfoundation.org



For a Complete Report

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