3-Methylcrotonyl-CoA carboxylase deficiency

A rare metabolic disorder

3-Methylcrotonyl-CoA carboxylase deficiency
Synonyms	3-MCC deficiency, Methylcrotonylglycinuria
Pronounce
Specialty	Medical genetics
Symptoms	Developmental delay, hypotonia, vomiting, lethargy, seizures
Complications	N/A
Onset	Infancy or early childhood
Duration	Chronic
Types	N/A
Causes	Mutations in the MCCC1 or MCCC2 genes
Risks
Diagnosis	Newborn screening, urine organic acid analysis, genetic testing
Differential diagnosis
Prevention
Treatment	Dietary management, carnitine supplementation
Medication
Prognosis	Generally good with treatment
Frequency	1 in 50,000 to 1 in 100,000
Deaths	Rare

3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency) is a rare autosomal recessive metabolic disorder that affects the body's ability to break down certain proteins. It is caused by a deficiency of the enzyme 3-methylcrotonyl-CoA carboxylase, which is involved in the leucine degradation pathway.

Pathophysiology

3-Methylcrotonyl-CoA carboxylase is an enzyme that catalyzes the carboxylation of 3-methylcrotonyl-CoA to 3-methylglutaconyl-CoA. This reaction is a crucial step in the catabolism of the amino acid leucine. In individuals with 3-MCC deficiency, the enzyme is either absent or not functioning properly, leading to the accumulation of toxic metabolites such as 3-methylcrotonyl-CoA and 3-hydroxyisovaleric acid.

Genetics

3-MCC deficiency is inherited in an autosomal recessive pattern, meaning that both copies of the gene in each cell have mutations. The gene associated with this condition is the MCCC1 or MCCC2 gene, which provides instructions for making the two subunits of the 3-methylcrotonyl-CoA carboxylase enzyme.

Clinical Presentation

The clinical presentation of 3-MCC deficiency can vary widely. Some individuals may remain asymptomatic, while others may experience symptoms such as hypotonia, developmental delay, vomiting, lethargy, and seizures. In severe cases, metabolic crises can occur, which may lead to coma or even death.

Diagnosis

Diagnosis of 3-MCC deficiency is typically made through newborn screening programs that detect elevated levels of 3-hydroxyisovaleric acid in the blood or urine. Confirmatory testing involves genetic testing to identify mutations in the MCCC1 or MCCC2 genes.

Management

Management of 3-MCC deficiency involves dietary restrictions to limit the intake of leucine, along with supplementation of carnitine to help remove toxic metabolites from the body. Regular monitoring by a metabolic specialist is recommended to prevent metabolic crises.

Prognosis

The prognosis for individuals with 3-MCC deficiency varies. Many individuals with the condition lead normal lives with appropriate management, while others may experience significant health challenges.

Related pages

• Metabolic disorder
• Amino acid metabolism
• Newborn screening

NIH genetic and rare disease info

• NIH info on 3-Methylcrotonyl-CoA carboxylase deficiency

3-Methylcrotonyl-CoA carboxylase deficiency is a rare disease.