3-Methylglutaconic aciduria

A group of metabolic disorders characterized by the accumulation of 3-methylglutaconic acid in the urine

3-Methylglutaconic aciduria is a group of rare metabolic disorders characterized by the accumulation of 3-methylglutaconic acid in the urine. These disorders are often associated with defects in the mitochondria, the energy-producing structures within cells.

Classification

3-Methylglutaconic aciduria is classified into several types based on the underlying genetic cause and clinical presentation:

• Type I: Also known as Barth syndrome, this type is linked to mutations in the TAZ gene and is characterized by cardiomyopathy, neutropenia, and skeletal myopathy.
• Type II: Also known as Costeff syndrome, it is associated with mutations in the OPA3 gene and presents with optic atrophy, movement disorders, and cognitive impairment.
• Type III: This type is less well-defined and includes a variety of symptoms such as ataxia, spasticity, and dystonia.
• Type IV: Also known as MEGDEL syndrome, it is caused by mutations in the SERAC1 gene and is characterized by deafness, encephalopathy, and leukodystrophy.
• Type V: This type is associated with mutations in the DNAJC19 gene and presents with dilated cardiomyopathy, growth retardation, and male genital anomalies.

Pathophysiology

The accumulation of 3-methylglutaconic acid is due to defects in the mitochondrial respiratory chain or other mitochondrial functions. These defects lead to impaired energy production and increased production of organic acids, including 3-methylglutaconic acid.

Clinical Features

The clinical features of 3-methylglutaconic aciduria vary depending on the type and severity of the disorder. Common symptoms include:

• Developmental delay
• Neurological abnormalities
• Muscle weakness
• Cardiomyopathy
• Hearing loss

Diagnosis

Diagnosis is typically made through the detection of elevated levels of 3-methylglutaconic acid in the urine using gas chromatography-mass spectrometry (GC-MS). Genetic testing can confirm the specific type of 3-methylglutaconic aciduria by identifying mutations in the associated genes.

Management

Management of 3-methylglutaconic aciduria is primarily supportive and symptomatic. This may include:

• Nutritional support
• Physical therapy
• Cardiac management
• Hearing aids for hearing loss

Prognosis

The prognosis of 3-methylglutaconic aciduria varies widely depending on the type and severity of the disorder. Some individuals may have a relatively mild course, while others may experience significant disability and reduced life expectancy.

Related pages

• Mitochondrial disease
• Organic acidemia
• Inborn errors of metabolism

Gallery

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  Structure of 3-methylglutaconic acid

3-Methylglutaconic aciduria

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  3-methylglutaconic acid structure