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
www.oaanews.org

Save Babies through Screening Foundation
www.savebabies.org

Genetic Alliance
www.geneticalliance.org

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