Organic Acid Disorders |
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| Disease Name | 3-methylcrotonyl-CoA carboxylase deficiency |
| Alternate name(s) | 3-methylcrotonylglycinuria |
| Acronym | 3-MCC |
| Disease Classification | Organic Acid Disorder |
| Variants | Late-onset form |
| Variant name | Late-onset 3-methylcrotonyl-CoA carboxylase deficiency |
| Symptom onset | Many individuals remain asymptomatic into adulthood. Others present in late infancy (generally after 3 months). |
| Symptoms | Infants can present with a Reye-like syndrome of ketoacidosis, hypoglycemia, hyperammonemia which can lead to seizures, coma and possibly death. Others present with failure to thrive, hypotonia or spasticity. Late-onset 3-MCC may present as developmental delay without Reye-like syndrome. Symptomatic adults often report general weakness and fatigue. Many individuals are asymptomatic. |
| Natural history without treatment | Primary manifestations appear to be muscular hypotonia and atrophy. Individuals with Reye-like illnesses may die or suffer neurologic insult during these episodes. |
| Natural history with treatment | Once over the initial crisis, most individuals have been intellectually normal. It is uncertain whether treatment modifies disease course. |
| Treatment | Protein restricted diet. Leucine-free medical foods. Possible carnitine supplementation. Giving treatment to asymptomatic individuals is of questionable value. |
| Other | Newborn screening has led to the diagnosis of asymptomatic women whose infants have transiently elevated isovalerylcarnitine. |
| Physical phenotype | None |
| Inheritance | Autosomal recessive |
| General population incidence | 1:50,000 |
| Ethnic differences | No known population at increase risk |
| Population | N/A |
| Ethnic incidence | N/A |
| Enzyme location | Inner membrane of the mitochondria, liver and kidney. |
| Enzyme Function | Breakdown of leucine |
| Missing Enzyme | 3-methylcrotonyl-CoA carboxylase |
| Metabolite changes | IIncreased 3-hydroxyisovaleric acid, increased 3-methylcrotonylglycine. |
| Gene | MCCA/MCCB |
| Gene location | 3q25-q27, 5q12-q13.1 |
| DNA testing available | Sequencing available internationally |
| DNA testing detail | No common mutations |
| Prenatal testing | May be possible for at-risk pregnancies using enzymatic analysis. |
| MS/MS Profile | C5:1 (tigyl or 3-methylcrotonyl carnitine) elevated C5-OH (3-hydroxy-2-methylbutyryl carnitine)- elevated |
| OMIM Link | www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=210200 |
| Genetests Link | www.genetests.org |
| Support Group | Organic Acidemia Association Save Babies through Screening Foundation |
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