3-methylcrotonyl-CoA carboxylase 1 deficiency

What is 3-MCC Deficiency?

3-methylcrotonyl-CoA carboxylase (MCC) deficiency, also known as 3-MCC or MCCC1 deficiency, is a rare inherited disorder of leucine metabolism. This condition affects the body's ability to break down certain proteins properly.

Causes and Symptoms

The MCC enzyme plays a crucial role in breaking down leucine, an essential amino acid found in many protein-rich foods. In people with 3-MCC deficiency, the MCC enzyme is either missing or not working properly, leading to a buildup of toxic substances in the body.

Symptoms of 3-MCC deficiency can vary widely and may include:

• Feeding difficulties and delayed development
• Vomiting and excessive tiredness (lethargy)
• Weak muscle tone and poor appetite
• Behavior changes, such as getting upset easily
• Floppy arms and legs in infancy
• Respiratory insufficiency and spasticity

Clinical Presentation

The clinical presentation of 3-MCC deficiency can range from a severe metabolic crisis in infancy to an asymptomatic or mildly symptomatic condition. In some cases, the disorder may not be diagnosed until later in life.

Genetic Basis

3-MCC deficiency is caused by mutations in the MCCC1 gene, which codes for the MCC enzyme. This genetic defect leads to a deficiency of the MCC enzyme, resulting in the accumulation of toxic substances and the manifestation of symptoms.

References

• [4] What is 3MCC? 3-methylcrotonyl-CoA carboxylase deficiency (3-MCC) is a condition in which the body is unable to break down certain proteins properly.
• [5] May 29, 2012 — Isolated 3-methylcrotonyl-CoA carboxylase (MCC) deficiency is an autosomal recessive disorder of leucine metabolism caused by mutations in MCCC1 ...
• [9] Mar 7, 2024 — 3-methylcrotonyl-CoA carboxylase deficiency (also called MCC deficiency) is an inherited disorder in which the body is unable to process ...

Early Signs and Symptoms

The signs and symptoms of 3-methylcrotonyl-CoA carboxylase 1 (3-MCC) deficiency can vary among individuals, but some common early signs include:

• Poor appetite [4]
• Sleeping longer or more often [6][9]
• Tiredness [4][6]
• Behavior changes [4][6]
• Irritability [1][4]
• Muscle weakness (known as hypotonia) [3][7]

In some cases, individuals with 3-MCC deficiency may also experience:

• Vomiting [3][5][7]
• Metabolic crisis, which can lead to more severe symptoms such as:
  • Coma [2]
  • Apnea [2]
  • Neurological abnormalities (e.g. metabolic stroke, hemiparesis, and encephalopathy) [2]
  • Weakness [2]

It's worth noting that some individuals with 3-MCC deficiency may not show any signs or symptoms at all, especially in the early stages of the condition [8].

References

[1] Context result 1 [2] Context result 2 [3] Context result 3 [4] Context result 4 [5] Context result 5 [6] Context result 6 [7] Context result 7 [8] Context result 8 [9] Context result 9

Diagnostic Tests for 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency

3-Methylcrotonyl-CoA carboxylase 1 deficiency is a genetic disorder that can be diagnosed through various tests. Here are some of the diagnostic tests used to confirm this condition:

• Urine Organic Acid Analysis: This test detects elevated levels of specific organic acids, such as 3-hydroxyisovaleric acid and 3-methylcrotonylglycine, in the urine. [12][14]
• Plasma Acylcarnitine Profile: This test measures the levels of certain acylcarnitines in the blood, which can help confirm the diagnosis of 3-MCC deficiency. [15]
• Gas Chromatography or Mass Spectrometry: These tests are used to detect and quantify specific organic acids in the urine, helping to confirm the diagnosis of 3-MCC deficiency. [12][14]
• Liquid Chromatography-Tandem Mass Spectrometry: This test is used to analyze the blood for specific metabolites associated with 3-MCC deficiency. [12]

These diagnostic tests can be performed on various samples, including urine, blood, or skin samples. The results of these tests can help confirm the diagnosis of 3-methylcrotonyl-CoA carboxylase 1 deficiency.

References:

[12] Detection of organic acids in urine using gas chromatography or mass spectrometry and analysis of the blood by liquid chromatography-tandem mass spectrometry. [14] Diagnosis of 3-MCC through newborn screening via the heel prick test taken 48-72 hours after birth. [15] Further testing, including urine organic acid analysis and plasma acylcarnitine profile, can confirm the diagnosis by detecting elevated levels of specific metabolites associated with the disorder.

Treatment Options for 3-Methylcrotonyl-CoA Carboxylase Deficiency

The treatment for 3-methylcrotonyl-CoA carboxylase (3MCC) deficiency involves reducing dietary leucine intake and sometimes a general protein-restricted diet. A special leucine-depleted formula may be used to manage the condition.

• Leucine restriction: Reducing dietary leucine intake is a crucial aspect of treatment for 3MCC deficiency. This can be achieved through a special leucine-depleted formula or by instituting a general protein-restricted diet [7].
• Dietary management: A food plan low in leucine may be necessary to manage the condition, especially in children who are diagnosed with 3-MCC at birth [6].

It's worth noting that early diagnosis and proper management of 3MCC deficiency can help reduce the risk of severe metabolic crisis. However, treatment is often not necessary in asymptomatic cases [3].

Differential Diagnosis of 3-MCC Deficiency

3-Methylcrotonyl-CoA carboxylase (3-MCC) deficiency is a rare genetic disorder that affects the metabolism of leucine. When diagnosing this condition, it's essential to consider other possible causes of similar symptoms. Here are some differential diagnoses for 3-MCC deficiency:

• 3-Hydroxy-3-methylglutaryl (HMG)-CoA lyase deficiency: This is another metabolic disorder that can cause similar symptoms, such as vomiting, seizures, and coma [6].
• Biotinidase deficiency: Although biotin-resistant 3-MCC deficiency is a distinct condition, biotinidase deficiency can also present with similar symptoms, including developmental delays and seizures [7].
• Other organic acidemias: Conditions like methylmalonic acidemia, propionic acidemia, and isovaleric acidemia can cause similar metabolic disturbances and symptoms [9].

Key Points to Consider

When diagnosing 3-MCC deficiency, it's crucial to consider the following:

• Clinical presentation: Symptoms such as vomiting, seizures, and coma are common in both 3-MCC deficiency and other differential diagnoses.
• Laboratory findings: Elevated levels of 3-methylcrotonylglycine (3-MCG) and 3-hydroxyisovaleric acid (3-HIVA) can be indicative of 3-MCC deficiency, but similar metabolites may also be present in other conditions [9].
• Genetic testing: Molecular genetic analysis is essential to confirm the diagnosis of 3-MCC deficiency and distinguish it from other differential diagnoses.

References

[6] - This condition has a similar presentation to 3-MCC deficiency, with symptoms such as vomiting, seizures, and coma. [7] - Biotinidase deficiency can present with developmental delays and seizures, which are also common in 3-MCC deficiency. [9] - Other organic acidemias, such as methylmalonic acidemia, propionic acidemia, and isovaleric acidemia, can cause similar metabolic disturbances and symptoms.

Note: The above answer is based on the context provided, which includes information about differential diagnoses for 3-MCC deficiency.