What are the other Names for this Condition? (Also known as/Synonyms)

• 3-MCC Deficiency Disorder
• 3-Methylcrotonyl-Coenzyme A Carboxylase Deficiency Disorder
• Isolated 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder

What is 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder? (Definition/Background Information)

• 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) is a genetic metabolic condition that impairs the body's ability to break down leucine, an amino acid found in protein. It occurs due to mutations in either the MCCC1 or MCCC2 genes, leading to a deficiency in the enzyme 3-methylcrotonyl-CoA carboxylase.
• This enzyme is essential for processing leucine, and when it is deficient, harmful byproducts can accumulate, potentially leading to metabolic crises. The condition is inherited in an autosomal recessive pattern, meaning both copies of the gene must be mutated for symptoms to appear.
• Symptoms of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder can vary widely, ranging from feeding difficulties, vomiting, lethargy, and hypotonia in infancy to more severe issues like seizures, breathing problems, and developmental delays if untreated. A diagnosis is typically made through newborn screening and confirmed with genetic testing for MCCC1 or MCCC2 mutations.
• The complications can include metabolic crises, which can lead to coma or death if untreated. Treatment often involves a low-leucine diet, frequent feedings, and supplements like L-carnitine to manage symptoms. With early detection and proper management, the prognosis is generally good, and many individuals may remain asymptomatic throughout life.

Who gets 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder? (Age and Sex Distribution)

• 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) can affect individuals of any age and sex.
• It is often identified in infancy or early childhood, especially through newborn screening programs, but some individuals may not develop symptoms until adulthood. In many cases, people may never exhibit symptoms despite carrying the genetic mutation.
• There is no specific gender predisposition, as 3-MCC is inherited in an autosomal recessive manner, meaning it affects males and females equally.
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder? (Predisposing Factors)

• The primary risk factor for developing 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) is having inherited two mutated copies of the MCCC1 or MCCC2 genes, one from each parent, due to its autosomal recessive inheritance pattern.
• If both parents are carriers of a defective gene, there is a 25% chance with each pregnancy that the child will inherit the disorder. A family history of 3-MCC or being born to parents who are known carriers of the gene mutations increases the risk. There are no known environmental or lifestyle-related factors that influence the likelihood of developing 3-MCC.

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder? (Etiology)

3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) is caused by mutations in either the MCCC1 or MCCC2 genes.

• These genes provide instructions for making the two subunits of the enzyme 3-methylcrotonyl-CoA carboxylase, which plays a critical role in breaking down leucine, an amino acid found in protein. When mutations occur, the activity of this enzyme is reduced or lost, preventing the proper breakdown of leucine.
• As a result, toxic byproducts accumulate in the body, which can lead to various symptoms and complications. 3-MCC is inherited in an autosomal recessive manner, meaning that both copies of the affected gene must be mutated for the disorder to develop.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder?

The signs and symptoms of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) can vary greatly among affected individuals. Common symptoms that may develop during infancy or early childhood include:

• Feeding difficulties
• Vomiting
• Lethargy (excessive tiredness)
• Weak muscle tone (hypotonia)
• Developmental delays

In more severe cases, especially if untreated, symptoms can escalate to:

• Seizures
• Breathing difficulties
• Coma

Some individuals may experience episodes of "metabolic crisis," characterized by poor appetite, lack of energy, irritability, nausea, and vomiting. However, many people with the disorder may remain asymptomatic throughout their lives, identified only through newborn screening.

How is 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder Diagnosed?

• 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) is often diagnosed through newborn screening, which detects elevated levels of specific metabolites associated with the disorder.
• If screening results suggest 3-MCC, further testing, including urine organic acid analysis and plasma acylcarnitine profile, can confirm the diagnosis by identifying abnormal metabolic byproducts.
• Genetic testing of the MCCC1 and MCCC2 genes is also used to identify the specific mutations responsible for the condition.

In cases where symptoms develop later in life, diagnosis may be based on clinical presentation, metabolic tests, and confirmed with genetic analysis.

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder?

The possible complications of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) can be severe, especially if the condition goes untreated. Potential complications include:

• Metabolic crises, characterized by poor appetite, lethargy, irritability, nausea, and vomiting, which can lead to serious health issues.
• Seizures, which may result from metabolic imbalances.
• Breathing difficulties, potentially requiring medical intervention.
• Developmental delays, affecting motor skills and cognitive function.
• Coma, which can be life-threatening in extreme cases.
• Death, if metabolic crises or severe symptoms are not managed promptly.

Early detection and proper treatment are key to reducing the risk of these complications.

How is 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder Treated?

Treatment for 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) focuses on managing symptoms and preventing metabolic crises. Common treatments include:

• Frequent feedings: To prevent long periods without food, which can trigger symptoms or metabolic crises.
• Low-leucine diet: Restricting leucine intake, an amino acid found in protein, helps reduce the accumulation of harmful byproducts.
• L-carnitine supplements: These supplements support the body in eliminating toxic compounds and improve energy production.
• Emergency care during illness: During times of stress, such as infections or fasting, affected individuals may need immediate medical care to prevent complications like seizures or coma.

With early diagnosis and proper management, most individuals with 3-MCC can live normal, healthy lives.

How can 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder be Prevented?

Preventing 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) involves genetic and prenatal measures:

• Genetic Counseling: For families with a history of 3-MCC or known carrier status, genetic counseling can provide information on the risk of passing the condition to offspring and discuss options.
• Carrier Screening: Individuals planning to start a family can undergo carrier screening to determine if they carry mutations in the MCCC1 or MCCC2 genes.
• Newborn Screening: Routine newborn screening can detect 3-MCC early, allowing for prompt intervention and management to prevent complications.

Since 3-MCC is inherited in an autosomal recessive pattern, there is no way to prevent the genetic mutations themselves, but these measures can help manage the condition effectively and minimize its impact. Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder? (Outcomes/Resolutions)

The prognosis of 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder (3-MCC) varies depending on early diagnosis and management. With timely intervention:

• Good Prognosis: Many individuals with 3-MCC who are diagnosed early and adhere to treatment, including a low-leucine diet and frequent feedings, can lead normal, healthy lives without significant symptoms.
• If an episode of “metabolic crisis” is not treated promptly, the affected individual may develop complications and even succumb to the 3-MCC Deficiency Disorder
• If untreated or diagnosed late, the disorder can lead to severe complications like developmental delays, seizures, and in extreme cases, coma or death.
• Asymptomatic Individuals: Some people may remain asymptomatic despite carrying the genetic mutations, especially if identified through newborn screening.

Overall, with proper management, the long-term outlook for individuals with 3-MCC is generally positive, and many can have a quality life without major health issues.

Additional and Relevant Useful Information for 3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder:

3-Methylcrotonyl-CoA Carboxylase Deficiency Disorder is also known by the following names:

• 3MCC
• 3-Methylcrotonyl-Coa Carboxylase 1 Deficiency Disorder
• 3-Methylcrotonylglycinuria
• MCC Deficiency Disorder
• MCCD Disorder

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/