# The Genetics of 3 Alpha Methylcrotonyl-CoA Carboxylase 2 Deficiency: What We Know So Far
Alpha methylcrotonyl-CoA carboxylase (MCC) is a crucial enzyme in the leucine catabolic pathway, which is responsible for breaking down the amino acid leucine into acetyl-CoA and acetoacetate. MCC is composed of two subunits, MCC alpha and MCC beta, and mutations in either subunit can cause MCC deficiency. MCC deficiency is a rare genetic metabolic disorder that affects the breakdown of leucine, resulting in the buildup of toxic metabolites in the body. This article will explore the genetics of 3 alpha methylcrotonyl-CoA carboxylase 2 deficiency and what we know so far.
## Understanding MCC Deficiency
MCC deficiency is a rare genetic metabolic disorder that affects the catabolic pathway of the amino acid leucine. The disorder is caused by a deficiency or malfunction of the MCC enzyme, which is responsible for catalyzing the carboxylation of alpha-methylcrotonyl-CoA to its final product, Beta-hydroxy-beta-methylglutaryl-CoA. MCC deficiency is caused mainly due to mutations in the MCC alpha (MCCA) or MCC beta (MCCB) genes.
## The Genetics of MCC Deficiency
MCC deficiency is inherited in an autosomal recessive pattern, which means that both parents must carry one copy of the mutated gene for the child to inherit the disorder. The MCC alpha (MCCA) and MCC beta (MCCB) genes are located on two different chromosomes, and mutations in either gene can cause MCC deficiency. The MCCA gene is located on chromosome 3q27.1 and consists of eight exons, while the MCCB gene is located on chromosome 5q13.2 and consists of ten exons.
## Types of MCC Deficiency
There are two types of MCC deficiency: MCC deficiency type I and MCC deficiency type II. Type I MCC deficiency results from a complete deficiency in MCC activity due to the absence or severe reduction in the amount of functional MCC protein. Type II MCC deficiency is caused by a partial reduction in MCC activity.
## Diagnosis of MCC Deficiency
MCC deficiency is diagnosed by measuring the levels of organic acids in a patient’s urine and blood. Elevated levels of 3-hydroxyisovaleric acid, 3-hydroxyisovaleryl carnitine, and tiglylglycine are indicative of MCC deficiency. A definitive diagnosis is made by molecular genetic testing of the MCCA or MCCB genes.
## Management of MCC Deficiency
There is currently no cure for MCC deficiency, and treatment involves the management of symptoms and prevention of metabolic crises. Management typically involves a strict low protein, low leucine diet, and supplementation with carnitine, biotin, and thiamine. Patients should also be monitored for the development of metabolic crises, which can be life-threatening.
## Research Into MCC Deficiency
Research into the genetics of MCC deficiency is ongoing. Studies have identified various mutations in the MCCA and MCCB genes that cause MCC deficiency. There is also ongoing research into the development of new treatments for MCC deficiency, including gene therapy and enzyme replacement therapy.
## Conclusion
MCC deficiency is a rare genetic metabolic disorder caused by a deficiency or malfunction of the MCC enzyme, which is responsible for catalyzing the carboxylation of alpha-methylcrotonyl-CoA. MCC deficiency is inherited in an autosomal recessive pattern, and mutations in the MCCA or MCCB genes can cause the disorder. Management of MCC deficiency involves a strict low protein, low leucine diet, and supplementation with carnitine, biotin, and thiamine. Ongoing research into the genetics of MCC deficiency may lead to new treatments for the disorder in the future.
## FAQs
1. What causes MCC deficiency?
MCC deficiency is caused by a deficiency or malfunction of the MCC enzyme, which is responsible for catalyzing the carboxylation of alpha-methylcrotonyl-CoA.
2. Is MCC deficiency a common genetic disorder?
No, MCC deficiency is a rare genetic metabolic disorder.
3. How is MCC deficiency diagnosed?
MCC deficiency is diagnosed by measuring the levels of organic acids in a patient’s urine and blood. A definitive diagnosis is made by molecular genetic testing of the MCCA or MCCB genes.
4. Is there a cure for MCC deficiency?
Currently, there is no cure for MCC deficiency, and treatment involves the management of symptoms and prevention of metabolic crises.
5. What is the outlook for individuals with MCC deficiency?
The outlook for individuals with MCC deficiency varies depending on the severity of the disorder and the degree of metabolic control achieved through diet and supplementation. Ongoing research may lead to new treatments for the disorder in the future.
**References**
1. Arnoux JB, Waniewski S, Quadir R, et al. Role of MCC defection in metabolic disorder management. Orphanet J Rare Diseases. 2013;8(10).
2. Van Hove JL. Alpha-Methylcrotonyl-CoA Carboxylase Deficiency. 2004 Aug 6 [updated 2014 Oct 23]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2021.
3. Sarafoglou K, Matern D, Redlinger-Grosse K, et al. Alpha-Methylcrotonyl CoA Carboxylase (MCC) Deficiency: Management and Outcome. J Inherit Metab Dis. 2010;33:523-30.
