Organic Acid Disorders |
|
| Disease Name | Isovaleric acidemia |
| Alternate name(s) | Isovaleric acid CoA dehydrogenase deficiency |
| Acronym | IVA |
| Disease Classification | Organic Acid Disorder |
| Variants | Yes |
| Variant name | Chronic intermittent form |
| Symptom onset | Infancy (in the acute neonatal form). The chronic intermittent form presents later in infancy or in childhood. |
| Symptoms | Episodic overwhelming illness with vomiting, ketosis, acidosis and coma. Hematological abnormalities include leucopenia, thrombocytopenia and possible anemia. |
| Natural history without treatment | About 50% of patients with the acute neonatal form will die during their first episode. Survivors may have neurological damage though several have made complete recoveries. Patients with the chronic form may have neurologic damage, but the majority of patients are developmentally normal. |
| Natural history with treatment | Intellectual prognosis depends on early diagnosis and treatment and subsequently on long-term compliance. If treated appropriately, most will have normal development. |
| Treatment | Low protein diet with restricted leucine intake, glycine supplementation and possible carnitine supplementation. |
| Other | Sometimes a “sweaty feet” odor is reported during an acute crisis. |
| Physical phenotype | No obvious dysmorphic features. |
| Inheritance | Autosomal recessive |
| General population incidence | 1:230,000 |
| Ethnic differences | None known |
| Population | N/A |
| Ethnic incidence | N/A |
| Enzyme location | N/A |
| Enzyme Function | Isovaleryl-CoA dehydrogenase is the first step in the branched chain organic acid metabolism of leucine. |
| Missing Enzyme | Isovaleryl-CoA dehydrogenase |
| Metabolite changes | Urinary isovaleryl glycine, 3-hydroxysoraline acid, increased isovaleric acid in blood. During acute attacks, 4-hydroxyisovaleric acid, mesaconic acid, and methylsuccinic acid, isovalerylglycine and 3-hydroxyisovaleric acid are present. |
| Gene | IVD |
| Gene location | 15q14-15 |
| DNA testing available | No |
| DNA testing detail | N/A |
| Prenatal testing | Enzyme analysis by GCMS in amniotic fluid or CVS tissue. |
| MS/MS Profile | Elevated C5 isovaleryl carnitine |
| OMIM Link | www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=243500 |
| Genetests Link | www.genetests.org |
| Support Group | Organic Acidemia Association Save Babies through Screening Foundation |
|
|
