Summary about Disease
3-Methylcrotonyl-CoA carboxylase deficiency (3-MCC deficiency) is an inherited metabolic disorder that prevents the body from properly processing leucine, an essential amino acid. This deficiency can lead to a buildup of harmful substances, potentially causing various health problems. The severity of the condition varies widely, with some individuals experiencing no symptoms (asymptomatic) and others suffering from severe complications.
Symptoms
Symptoms can vary widely and may include:
Poor feeding
Vomiting
Lethargy (lack of energy)
Hypotonia (floppy muscle tone)
Developmental delay
Seizures
Metabolic acidosis (excess acid in body fluids)
Coma (in severe cases)
Skin rashes Some individuals may remain asymptomatic throughout their lives. Symptoms can be triggered by illness, stress, or increased protein intake.
Causes
3-MCC deficiency is caused by mutations in either the MCCC1 gene or the MCCC2 gene. These genes provide instructions for making subunits of the 3-methylcrotonyl-CoA carboxylase enzyme. Mutations in these genes lead to a deficiency or complete absence of the functional enzyme. This impairs the breakdown of leucine. It is inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for their child to be affected.
Medicine Used
4. Medicine used There is no specific medicine to cure 3-MCC deficiency. Treatment focuses on managing symptoms and preventing metabolic crises. Medical interventions may include:
L-Carnitine supplementation: Helps remove accumulating toxic metabolites.
Dietary management: A low-protein diet, specifically limiting leucine intake, can be crucial.
Emergency protocol: During illness or metabolic crisis, intravenous fluids, glucose, and close monitoring are essential to prevent complications.
Supplements: Additional supplements such as biotin might be recommended, although its efficacy is debated.
Is Communicable
No. 3-MCC deficiency is a genetic disorder and is not contagious. It cannot be spread from person to person.
Precautions
Dietary management: Strict adherence to the prescribed low-leucine diet is vital.
Avoidance of fasting: Prolonged periods without food can trigger metabolic crises.
Emergency plan: A detailed plan for managing illness or stress, including when to seek medical attention, should be in place.
Regular monitoring: Regular follow-up appointments with a metabolic specialist are necessary to monitor the condition and adjust treatment as needed.
Genetic counseling: Consider genetic counseling for families with a history of 3-MCC deficiency.
How long does an outbreak last?
There are no outbreaks with this disorder. The symptoms manifest when there are an elevated amount of the amino acid, Leucine.
How is it diagnosed?
Diagnosis typically involves:
Newborn screening: Many regions include 3-MCC deficiency in newborn screening programs, detecting elevated levels of 3-hydroxyisovaleric acid in blood spots.
Urine organic acid analysis: Detects abnormal metabolites in the urine.
Plasma acylcarnitine profile: Measures levels of various acylcarnitines in the blood.
Enzyme assay: Measures the activity of the 3-methylcrotonyl-CoA carboxylase enzyme in fibroblasts or lymphocytes.
Genetic testing: Confirms the diagnosis by identifying mutations in the MCCC1 or MCCC2 genes.
Timeline of Symptoms
9. Timeline of symptoms The onset and severity of symptoms vary greatly:
Newborn period: Some individuals present shortly after birth with poor feeding, vomiting, and lethargy.
Infancy/childhood: Others may develop symptoms later in infancy or childhood, often triggered by illness or stress.
Asymptomatic: Some individuals may never develop noticeable symptoms. The exact timeline is highly variable and depends on the severity of the enzyme deficiency and individual factors.
Important Considerations
Early diagnosis and management are crucial for preventing severe complications.
Even asymptomatic individuals require monitoring and may need dietary adjustments during periods of stress or illness.
Lifelong adherence to dietary and medical recommendations is typically necessary.
The prognosis varies widely, with early intervention leading to better outcomes.
Support groups and resources for families affected by metabolic disorders can provide valuable assistance.
Carrier testing is available for individuals with a family history of 3-MCC deficiency.