Isovaleric acidemia

DiseaseDisorder infobox
Name = Isovaleric acidemia
ICD10 = ICD10|E|71|1|e|70
ICD9 = ICD9|270.3
ICDO =

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Caption = Isovaleric acid
Width = 135
OMIM = 243500
MedlinePlus =
eMedicineSubj =
eMedicineTopic =
DiseasesDB = 29840

Isovaleric acidemia, also called isovaleric aciduria or isovaleric acid CoA dehydrogenase deficiency, [OMIM|243500] is a rare autosomal recessive [cite journal |pmid=17576084 |year=2007 |month=Sep |author=Lee, Yw; Lee, Dh; Vockley, J; Kim, Nd; Lee, Yk; Ki, Cs |title=Different spectrum of mutations of isovaleryl-CoA dehydrogenase (IVD) gene in Korean patients with isovaleric acidemia |volume=92 |issue=1-2 |pages=71–7 |doi=10.1016/j.ymgme.2007.05.003 |journal=Molecular genetics and metabolism] metabolic disorder which disrupts or prevents normal metabolism of the branched-chain amino acid leucine. It is a classical type of organic acidemia.cite journal |author=Dionisi-Vici C, Deodato F, Raschinger W, Rhead W, Wilcken B |title=Classical organic acidurias, propionic aciduria, methylmalonic aciduria, and isovaleric aciduria: long-term outcome and effects of expanded newborn screening using tandem mass spectrometry |journal=J Inherit Metab Dis. |volume=29 |issue=2-3 |pages=383–389 |year=2006 |pmid=16763906 |doi=10.1007/s10545-006-0278-z ]

ymptoms

A characteristic feature of isovaleric acidemia is a distinctive odor of sweaty feet. [cite journal |author=Tokatli A, Oskun T, Ozalp I |title=Isovaleric acidemia. Clinical presentation of 6 cases |journal=Turk J Pediatr. |volume=40 |issue=1 |pages=111–119 |year=1998 |pmid=9673537 ] This odor is caused by the buildup of a compound called isovaleric acid in affected individuals.

In about half of cases, the signs and symptoms of this disorder become apparent within a few days after birth and include poor feeding, vomiting, seizures, and lack of energy that can progress to coma. These medical problems are typically severe and can be life-threatening. In the other half of cases, the signs and symptoms of the disorder appear during childhood and may come and go over time. They are often triggered by an infection or by eating an increased amount of protein-rich foods.

The urine of newborns can be screened for isovaleric acidemia using mass spectrometry, allowing for early diagnosis.

Genetic prevalence

Isovaleric acidemia is estimated to affect at least 1 in 250,000 births in the United States. [http://ghr.nlm.nih.gov/condition=isovalericacidemia?wf=1]

The disorder has an autosomal recessive inheritance pattern, which means the defective gene is located on an autosome, and two copies of the gene - one from each parent - must be inherited to be affected by the disorder. The parents of a child with an autosomal recessive disorder are carriers of one copy of the defective gene, but are usually not affected by the disorder.

Mutations in both copies of the "IVD" gene result in isovaleric acidemia.

Pathophysiology

The enzyme encoded by "IVD", isovaleric acid-CoA dehydrogenase (EC number|1.3.99.10), plays an essential role in breaking down proteins from the diet. Specifically, the enzyme is responsible for the third step in processing leucine, an essential amino acid. If a mutation in the IVD gene reduces or eliminates the activity of this enzyme, the body is unable to break down leucine properly. As a result, isovaleric acid and related compounds build up to toxic levels, damaging the brain and nervous system.

References

ee also

* Maple syrup urine disease
* Methylmalonic acidemia
* Propionic acidemia

External links

* [http://www.oaanews.org Organic Acidemia Association]
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