3-methylglutaconic aciduria type 8

What is 3-Methylglutaconic Aciduria Type 8?

3-Methylglutaconic aciduria type 8 (MGCA8) is a rare and severe autosomal recessive metabolic disorder. It is characterized by the accumulation of 3-methylglutaconic acid in the body, leading to various clinical features.

Clinical Features:

• Hypotonia (low muscle tone)
• Abnormal movements
• Respiratory insufficiency
• Failure to thrive

These symptoms are typically present from birth and can lead to death in infancy if left untreated. MGCA8 is a rare disorder, and its exact prevalence is unknown.

Causes and Genetics:

MGCA8 is caused by homozygous mutations in the HTRA2 gene on chromosome 2p13. This genetic mutation affects the body's ability to break down certain amino acids, leading to the accumulation of toxic substances.

References:

• [1] Wortmann SB, Duran M, Anikster Y, Barth PG, Sperl W, Zschocke J, Morava E, Wevers RA. Inborn errors of metabolism with 3-methylglutaconic aciduria as discriminative feature: proper classification and nomenclature. J Inherit Metab Dis. 2013 Nov;36(6):923-8. doi: 10.1007/s10545-012-9580-0.
• [2] A 3-methylglutaconic aciduria that has_material_basis_in homozygous mutation in the HTRA2 gene on chromosome 2p13.

Note: The information provided is based on the search results and may not be an exhaustive list of all possible symptoms or characteristics of MGCA8.

Signs and Symptoms of 3-Methylglutaconic Aciduria Type 8

3-Methylglutaconic aciduria type 8 is a rare genetic disorder that affects the body's ability to produce energy in the mitochondria. The signs and symptoms of this condition can vary, but here are some common features:

• Hypotonia: Affected individuals often experience hypotonia, which is characterized by low muscle tone or weakness.
• Abnormal movements: Some people with 3-methylglutaconic aciduria type 8 may exhibit abnormal movements, such as tremors or seizures.
• Respiratory insufficiency: This condition can lead to respiratory problems, including apneic episodes (pauses in breathing).
• Lack of developmental progress: Affected individuals often experience a delay or lack of progress in their physical and mental development.
• Seizures: Seizures are a common symptom of 3-methylglutaconic aciduria type 8.

Additional symptoms

Some people with this condition may also experience:

• Microcephaly: A smaller-than-normal head size
• Sensorineural deafness: Hearing loss due to damage to the inner ear
• Bradycardia: A slower than normal heart rate
• Neutropenia: A lower-than-normal count of white blood cells

It's essential to note that each individual may experience a unique set of symptoms, and not everyone will exhibit all of these features.

References:

[1] - Features include hypotonia, abnormal movements, respiratory insufficiency with apneic episodes, and lack of developmental progress, often with seizures. Brain imaging is variable, but may show progressive cerebral atrophy. Laboratory studies show increased serum lactate and 3-methylglutaconic aciduria. [4] [2] - Symptoms include hypotonia, abnormal movements, respiratory insufficiency, lack of developmental progress, and seizures. Brain imaging may show progressive cerebral atrophy. [5] [3] - Affected individuals have hypotonia, failure to thrive, and neurodegeneration with loss of developmental milestones, as well as liver dysfunction. Some patients experience microcephaly, sensorineural deafness, bradycardia, and neutropenia. [9]

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Diagnostic Tests for 3-Methylglutaconic Aciduria Type 8

3-Methylglutaconic aciduria type 8 is a rare genetic disorder that affects the body's ability to break down certain amino acids. Diagnostic tests are essential for confirming the diagnosis of this condition.

• Clinical Genetic Test: A clinical genetic test offered by Intergen can detect mutations in the HTRA2 gene, which is associated with 3-methylglutaconic aciduria type 8 [1][4]. This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 17 genes associated with this condition [3][5].
• Targeted Mutation Analysis: Targeted mutation analysis of the HTRA2 gene can also be used for diagnosis. This involves Sanger sequencing and sequence analysis of the entire coding region [7].
• Biochemical Tests: Biochemical tests, such as urine organic acids screening, can help identify the presence of 3-methylglutaconic acid in the urine, which is a hallmark of this condition [6].

References:

[1] Clinical Genetic Test offered by Intergen for conditions (1): 3-methylglutaconic aciduria type 8; Testing genes (1): HTRA2 (2p13.1)

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

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

[4] Clinical Genetic Test offered by Intergen for conditions (1): 3-methylglutaconic aciduria type 8; Testing genes (1): HTRA2 (2p13.1)

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

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

[7] Diagnosis of 3-methylglutaconic aciduria type 8 (HTRA2 gene) ; Targeted mutation analysis. Sanger sequencing ; Sequence analysis: entire coding region. NGS ...

Based on the provided context, it appears that there is limited information available on the specific treatment for 3-methylglutaconic aciduria type 8.

However, according to search result [5], a clinical resource provides information about 3-methylglutaconic aciduria type 8 and its clinical features, HTRA2. Unfortunately, this resource does not provide detailed information on the drug treatment for this condition.

Search result [7] mentions that there is no effective treatment for 3-MGA type IV, which might be related to type 8, but it's unclear if this applies specifically to type 8. It also states that a leucine-restricted diet appears to be of no benefit.

Another search result [8] suggests that there is no specific effective treatment, but a low leucine or protein diet is advised for 3-MGAType II (Barth syndrome), which might be related to type 8. However, this information is not specific to type 8 and may not be applicable.

It's essential to consult the most recent medical literature or a healthcare professional for accurate and up-to-date information on the treatment of 3-methylglutaconic aciduria type 8.

References: * [5] Clinical resource with information about 3-methylglutaconic aciduria type 8 and its clinical features, HTRA2. * [7] At present there is no effective treatment for 3-MGA type IV and a leucine-restricted diet appears to be of no benefit. * [8] There is no specific effective treatment, but low leucine or protein diet is advised.

Differential Diagnosis of 3-Methylglutaconic Aciduria Type 8

3-Methylglutaconic aciduria (MGA) is a group of rare genetic disorders characterized by the accumulation of 3-methylglutaconic acid in the urine. MGA type 8, also known as 3-methylglutaconyl-CoA hydratase deficiency, is one of the subtypes of this disorder.

Differential Diagnosis

The differential diagnosis for MGA type 8 includes other metabolic disorders that can present with similar symptoms and laboratory findings. Some of these conditions include:

• Lysosomal storage disorders: These are a group of genetic disorders caused by defects in lysosomal function, leading to the accumulation of toxic substances in the body.
• Juvenile Huntington's disease: This is a rare genetic disorder characterized by progressive neurological deterioration, including chorea and cognitive decline.
• Metabolic diseases: Other metabolic disorders, such as urea cycle disorders or organic acidemias, can also present with similar symptoms.

Key Features

The key features that distinguish MGA type 8 from other conditions include:

• 3-Methylglutaconic aciduria: The presence of elevated levels of 3-methylglutaconic acid in the urine is a hallmark of this disorder.
• Neurological involvement: Patients with MGA type 8 often present with neurological symptoms, such as chorea or ataxia.
• Metabolic disturbances: This condition can also be associated with metabolic disturbances, including hyperammonemia and lactic acidosis.

References

• [4] 3-methylglutaconyl-CoA hydratase deficiency is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels 3-methylglutaconic acid in the urine.
• [7] 3-methylglutaconic aciduria can be diagnosed by analysis of urinary organic acid excretion but specific diagnosis of 3-MGA type IV requires exclusion of all other conditions.
• [8] Although very rare, MGCA should be considered in the differential diagnosis of late-onset leukoencephalopathy with ataxia and cognitive decline.