3-methylglutaconic aciduria type 5

What is 3-Methylglutaconic Aciduria Type 5?

3-Methylglutaconic aciduria type 5, also known as MGCA5, is a rare genetic disorder characterized by severe early-onset dilated cardiomyopathy (DCM) with conduction defects, including long QT syndrome. This condition typically affects infants and young children.

Key Features of MGCA5:

• Autosomal Recessive Inheritance: MGCA5 is inherited in an autosomal recessive pattern, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Dilated Cardiomyopathy: The primary feature of MGCA5 is dilated cardiomyopathy, which is characterized by a weakened heart muscle that leads to a decrease in cardiac function.
• Conduction Defects: Individuals with MGCA5 often experience conduction defects, including long QT syndrome, which can increase the risk of sudden cardiac death.

Other Types of 3-Methylglutaconic Aciduria

It's worth noting that there are other types of 3-methylglutaconic aciduria (MGA), which include types I-IV and type V. Each type has distinct features, but they all share a common underlying metabolic disorder characterized by impaired energy production in the mitochondria.

References:

• [1] - Characterized by severe early onset (before the age of three years) dilated cardiomyopathy (DCM) with conduction defects (long QT syndrome), non-compaction cardiomyopathy, and sudden death.
• [4] - 3-Methylglutaconic aciduria type V is an autosomal recessive disorder characterized by dilated or noncompaction cardiomyopathy in infancy or early childhood.
• [9] - 3-Methylglutaconic aciduria type V (MGCA5) is an autosomal recessive disorder characterized by the onset of dilated or noncompaction cardiomyopathy in infancy or early childhood.

Signs and Symptoms of 3-Methylglutaconic Aciduria Type 5

3-Methylglutaconic aciduria (MGA) type 5, also known as DCMA syndrome or MGA5, is a rare genetic disorder. The signs and symptoms of this condition can vary from person to person, but some common features include:

• Microcytic anemia: A type of anemia characterized by small red blood cells.
• Growth retardation: Slow growth and development in children.
• Mild ataxia: Difficulty with coordination and balance.
• Muscle weakness: Weakness or fatigue in the muscles.
• Genital anomalies in males: Abnormalities in the genital area, such as undescended testes.

These symptoms can be present from infancy to childhood. It's essential to note that not all individuals with MGA type 5 will exhibit these signs and symptoms, and some may have additional features not listed here.

References:

• [6] - The prevalence of MGA type 5 is unknown, but it is inherited in an autosomal recessive manner.
• [5] - Additional features include microcytic anemia, growth retardation, mild ataxia, muscle weakness, and genital anomalies in males.
• [4] - Other features include microcytic anemia, growth retardation, mild ataxia, mild muscle weakness, genital anomalies in males, and increased urinary excretion of 3-methylglutaconic acid.

Diagnostic Tests for 3-Methylglutaconic Aciduria Type 5

3-Methylglutaconic aciduria type 5 (MGCA5) is a rare genetic disorder, and its diagnosis can be challenging. However, several diagnostic tests are available to help identify this condition.

• Next-generation sequencing (NGS): This test utilizes NGS to detect single nucleotide and copy number variants in 17 genes associated with MGCA5 [2][6]. The test is designed to identify mutations in these genes that can cause the disorder.
• Urine organic acids test: This is a biochemical test that measures the levels of 3-methylglutaconic and 3-methylglutaric acids in urine. Elevated levels of these acids are indicative of MGCA5 [7][8].
• DNAJC19 gene testing: Specific genetic testing for the DNAJC19 gene can also be performed to diagnose MGCA5 [9].

Diagnostic Strategy

The recommended first-tier biochemical test is the urine organic acids test, which can help identify patients with elevated levels of 3-methylglutaconic and 3-methylglutaric acids. If this test is abnormal, further genetic testing may be necessary to confirm the diagnosis.

It's worth noting that establishing a molecular diagnosis for patients with MGCA5 requires a comprehensive approach, including biochemical and genetic testing [10].

References:

[2] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 17 genes associated with 3-methylglutaconic aciduria: AGK, ...

[6] This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 17 genes associated with 3-methylglutaconic aciduria: AGK, ...

[7] Diagnosis. Patients are identified by elevated urinary concentrations of 3-methylglutaconic and 3-methylglutaric acids.

[8] The recommended first-tier biochemical test is urine organic acids; order OAU / Organic Acids Screen, Random, Urine.

[9] DNAJC19 Gene 3-methylglutaconic aciduria type 5 NGS Genetic Test cost INR:20000 symptoms diagnosis.

[10] Follow up for abnormal biochemical results suggestive of 3-methylglutaconic aciduria (3-MGA). Establishing a molecular diagnosis for patients with 3-MGA.

Treatment Options for 3-Methylglutaconic Aciduria Type 5

According to the available information, there is no specific effective treatment for 3-methylglutaconic aciduria type 5 (MGCA5). However, some general treatment approaches may be considered.

• Low Leucine or Protein Diet: A low leucine or protein diet may be advised as a supportive measure to manage the condition. This approach is mentioned in [9] and [4], which suggest that reducing dietary intake of leucine or protein may help alleviate symptoms.
• Standard Medical Treatment: In some cases, improvement with standard medical treatment or complete resolution of dilated cardiomyopathy (DCM) has been reported. However, this information is limited to a few case reports, as mentioned in [8].

It's essential to note that the effectiveness and long-term outcomes of these treatment approaches are not well established for MGCA5 specifically. Further research is needed to determine the most effective management strategies for this condition.

References:

[4] - No specific effective treatment, but low leucine or protein diet is advised. [8] - Improvement with standard medical treatment or complete resolution of DCM has been reported in some cases. [9] - Same as [4], mentioning a rare X-linked genetic disease (Barth syndrome) and the need for a low leucine or protein diet.

Differential Diagnosis of 3-Methylglutaconic Aciduria Type 5