3-methylcrotonyl-CoA carboxylase 2 deficiency

What is 3-MCC Deficiency?

3-methylcrotonyl-CoA carboxylase 2 (MCCC2) deficiency, also known as 3-MCC deficiency, is a rare inherited disorder of leucine metabolism. This condition affects the body's ability to break down certain proteins properly [1].

Symptoms and Features

The symptoms and features of MCCC2 deficiency may include:

• Feeding difficulties
• Delayed development
• Vomiting
• Excessive tiredness (lethargy)
• Weak muscle tone (hypotonia)
• Poor appetite
• Sleeping longer or more often
• Tiredness
• Behavior changes
• Irritability
• Muscle weakness (hypotonia)
• Vomiting
• Muscle tightness [4]

Causes and Inheritance

MCCC2 deficiency is caused by changes in the MCCC1 or MCCC2 gene, which are inherited in an autosomal recessive manner. This means that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [5].

Enzyme Deficiency

In people with 3-MCC deficiency, the 3-MCC enzyme is either missing or not working properly. This enzyme's job is to help break down leucine, a type of amino acid found in proteins [7].

Gene and Enzyme Information

The MCCC2 gene provides instructions for making one part (the beta subunit) of an enzyme called 3-methylcrotonoyl-CoA carboxylase or MCC. This enzyme plays a crucial role in the breakdown of leucine, and its deficiency can lead to various symptoms and complications [9].

References:

[1] - Context result 2 [4] - Context result 4 [5] - Context result 5 [7] - Context result 7 [9] - Context result 9

Signs and Symptoms of 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency

3-Methylcrotonyl-CoA carboxylase 2 (MCCC2) deficiency is a rare genetic disorder that affects the body's ability to break down certain proteins properly. The signs and symptoms of this condition can vary among individuals, even within the same family.

Common Signs and Symptoms:

• Feeding difficulties [6]
• Delayed development [11]
• Vomiting [4][7]
• Excessive tiredness (lethargy) [4][7]
• Weak muscle tone (hypotonia) [4][7]
• Muscle spasms [9]
• Involuntary movements [9]
• Seizures [9]

Other Possible Symptoms:

• Poor appetite [8]
• Nausea and vomiting [8]
• Diarrhea [8]
• Extreme sleepiness [8]
• Irritable mood and behavior changes [8]

Important Note: The clinical presentation of MCCC2 deficiency can range from asymptomatic to neonatal onset with extreme neurological symptoms, and even fatal cases [10].

It's essential for individuals with suspected MCCC2 deficiency to receive early detection and lifelong management, following a low-protein diet and using appropriate supplements. This may prevent many complications associated with this condition [12]. In some cases, people with gene mutations that cause MCCC2 deficiency never experience any signs or symptoms of the disorder [12].

References: [4] - Search result 4 [6] - Search result 6 [7] - Search result 7 [8] - Search result 8 [9] - Search result 9 [10] - Search result 10 [11] - Search result 11 [12] - Search result 12

Diagnostic Tests for 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency

3-Methylcrotonyl-CoA carboxylase 2 (MCCC2) deficiency is a rare genetic disorder that can be diagnosed through various diagnostic tests. Here are some of the key diagnostic tests used to confirm this condition:

• Genetic Testing: Molecular genetic testing is available to identify two disease-causing alleles, which confirms the diagnosis of MCCC2 deficiency [1]. This test can be performed on a blood sample and is useful for patients who have concerning symptoms or abnormal screening results.
• Newborn Screening Programs: Newborn screening programs are available in the U.S. and some European countries to screen for MCCC2 deficiency [2].
• Clinical Examination and Specialized Blood and Urine Tests: This condition can be diagnosed through a clinical examination, as well as specialized blood and urine tests [8]. In some countries, this condition is screened for routinely.
• DNA Sequencing: DNA sequencing of the MCCC2 gene can be performed to confirm the diagnosis in cases where DNA from an affected child is unavailable [5].

It's essential to diagnose 3-MCC deficiency prior to the appearance of symptoms so that patients can receive appropriate intervention at the first sign of illness [7]. Genetic testing for 3MCC deficiency can be done on a blood sample, and it looks for changes in the DNA sequence of the MCCC2 gene [8].

References:

[1] Mar 7, 2024 — Genetic Testing Registry: 3-methylcrotonyl-CoA carboxylase 2 deficiency From the National Institutes of Health. Genetic and Rare Diseases ...

[2] Molecular genetic testing identifying two disease causing alleles confirms diagnosis. Newborn screening programs are available in the U.S. and some European ...

[5] Indications for Test. All MCC deficiency patients are candidates for this test. In cases where DNA from an affected child is unavailable, we will sequence the ...

[7] It is important to diagnose 3-MCC deficiency prior to the appearance of symptoms so that patients can receive appropriate intervention at the first sign of ...

[8] IS GENETIC TESTING AVAILABLE? Genetic testing for 3MCC deficiency can be done on a blood sample. Genetic testing, also called DNA testing, looks for changes ...

Treatment Options for 3-Methylcrotonyl-CoA Carboxylase 2 Deficiency

According to the search results, treatment for 3-methylcrotonyl-CoA carboxylase 2 deficiency (3-MCCD) involves reducing dietary leucine intake using a special leucine-depleted formula or instituting a general protein-restricted diet [9]. This is aimed at limiting the consumption of many foods, including high-protein food, which can help manage the condition [8].

In some cases, patients with 3-MCCD may develop secondary carnitine deficiency. In such instances, L-carnitine supplementation (100 mg/kg/day) is recommended to address this issue [12]. Additionally, treatment with glycine (175 mg /kg/day) can be used to enhance the elimination of 3-methylcrotonyl-CoA by conjugation to produce 3-MCG, which is excreted in the urine [12].

It's essential to note that most children diagnosed with 3-MCCD at birth never require special treatment and can live healthy lives without any intervention [6]. However, for those who do need treatment, a multidisciplinary approach involving healthcare professionals from various specialties may be necessary to manage the condition effectively.

References:

• [8] A Kowalik · 2018 · Cited by 2 — The dietary treatment of inborn errors of metabolism, including 3-MCC deficiency, requires limiting the consumption of many foods, including high-protein food.
• [9] Treatment of 3-MCC deficiency involves reducing dietary leucine intake using a special leucine-depleted formula or instituting a general protein restricted diet
• [12] Some subjects with 3-MCCD develop secondary carnitine deficiency, and L-carnitine supplementation (100 mg/kg/day) is recommended for these, while treatment with glycine (175 mg /kg/day) can be used to enhance the elimination of 3-methylcrotonyl-CoA by conjugation to produce 3-MCG, which is excreted in the urine.

Understanding Differential Diagnosis for 3-MCC2 Deficiency

Differential diagnosis refers to the process of ruling out other possible conditions that may present with similar symptoms, in order to arrive at a definitive diagnosis. In the case of 3-methylcrotonyl-CoA carboxylase 2 deficiency (3-MCC2), there are several conditions that can be considered as part of the differential diagnosis.

Conditions to Consider

• 3-Methylcrotonyl-CoA Carboxylase 1 Deficiency: This is a similar condition to 3-MCC2, caused by mutations in the MCCC1 gene. Symptoms may include feeding difficulties, delayed development, and weak muscle tone.
• Acute Hyperammonemia: This is a life-threatening condition characterized by high levels of ammonia in the blood. Symptoms may include vomiting, lethargy, and seizures.
• Hyperleucinemia: This is a condition characterized by high levels of leucine in the blood. Symptoms may include feeding difficulties, delayed development, and weak muscle tone.

Key Differences

While these conditions share some similarities with 3-MCC2, there are key differences that can help distinguish them:

• Genetic Cause: 3-MCC2 is caused by mutations in the MCCC2 gene, whereas 3-MCC1 is caused by mutations in the MCCC1 gene.
• Symptom Presentation: Acute hyperammonemia typically presents with more severe symptoms, such as seizures and coma, whereas hyperleucinemia may present with milder symptoms, such as feeding difficulties and delayed development.

Diagnostic Approach

To arrive at a definitive diagnosis of 3-MCC2, healthcare providers will typically follow a stepwise approach:

1. Clinical Evaluation: A thorough clinical evaluation is performed to assess the patient's overall health and identify any symptoms or signs that may be indicative of 3-MCC2.
2. Laboratory Tests: Laboratory tests are conducted to measure levels of ammonia, leucine, and other metabolites in the blood and urine.
3. Genetic Testing: Genetic testing is performed to confirm mutations in the MCCC2 gene.

By considering these conditions as part of the differential diagnosis for 3-MCC2, healthcare providers can ensure that patients receive an accurate and timely diagnosis, which is essential for effective management and treatment.

References

• [1] Mar 7, 2024 — Features of MCC deficiency may include feeding difficulties, delayed development, vomiting, excessive tiredness (lethargy), and weak muscle tone ...
• [3] 3-MCC deficiency is caused by changes in MCCC1 or MCCC2 gene and is inherited in an autosomal recessive manner.
• [5] Isolated 3-methylcrotonyl-CoA carboxylase deficiency: a review of the literature.