3-methylglutaconic aciduria type 3

What is 3-Methylglutaconic Aciduria Type 3?

3-Methylglutaconic aciduria type 3 (MGA III) is a rare genetic disorder that affects the body's ability to produce energy properly. It is characterized by a group of symptoms, including:

• Early-onset bilateral optic atrophy: This refers to vision problems that occur early in life, affecting both eyes.
• Later-onset spasticity: Spasticity is a condition where muscles become stiff and rigid, leading to movement difficulties.
• Mild to moderate intellectual disability: Individuals with MGA III may experience some cognitive impairment.

Causes and Effects

The disorder is caused by a genetic mutation that affects the production of energy in the body. As a result, individuals with MGA III have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria).

Symptoms and Signs

In addition to the above-mentioned symptoms, MGA III can also cause:

• Muscle spasms and weakness
• Frequent infections
• Weak muscles

Inheritance Pattern

MGA III is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.

References:

• [1] OMIM - 3-Methylglutaconic aciduria type III (MGCA3)
• [2] Sep 15, 2024 - 3-Methylglutaconic aciduria is caused by a group of inherited (genetic) conditions that prevent the body from making energy properly.
• [3] May 17, 2021 - As a result, they have elevated levels of acid in their blood (metabolic acidosis) and excrete large amounts of acid in their urine (aciduria).
• [4] Disease Overview. 3-methylglutaconic aciduria type III (MGA III) is an organic aciduria characterized by the association of optic atrophy and choreoathetosis.
• [5] The symptoms of 3-methylglutaconic aciduria type 3 include vision problems, movement problems, and mild to moderate intellectual disability.

Early-Onset Bilateral Optic Atrophy

The primary sign of 3-methylglutaconic aciduria type III (MGA III) is early-onset bilateral optic atrophy, which affects the optic nerves and leads to vision loss [4][5]. This condition typically presents in infancy or early childhood.

Later-Onset Spasticity

As the disease progresses, individuals with MGA III may experience later-onset spasticity, characterized by stiffness and rigidity of the muscles [11]. This symptom can manifest in various parts of the body, including the arms and legs.

Extrapyramidal Dysfunction

MGA III is also associated with extrapyramidal dysfunction, which affects the brain's ability to control movement. This can lead to symptoms such as tremors, muscle weakness, and coordination problems [7][11].

Cognitive Deficit

Individuals with MGA III may experience cognitive deficits, including delayed development and learning difficulties [12]. These cognitive impairments can be subtle and may not become apparent until early adulthood.

Other Clinical Features

In addition to the primary symptoms mentioned above, individuals with MGA III may also experience other clinical features, such as:

• Mild ataxia (uncoordinated movement)
• Spastic paraparesis (weakness or paralysis of the legs)
• Dysarthria (speech difficulties)
• Nystagmus (abnormal eye movements)

These symptoms can vary in severity and presentation among individuals with MGA III.

References

[4] 3-Methylglutaconic aciduria type III (MGCA3) is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity. [5] 3-methylglutaconic aciduria type III (MGA III) is an autosomal recessive condition and belongs to a group of conditions called organic acidurias. It is characterised by the association of optic degeneration and choreoathetosis with 3-methylglutaconic aciduria. [7] The 3-MGA-uria type III, or Costeff syndrome, is an autosomal recessive disorder with infantile bilateral optic atrophy, extrapyramidal signs, spasticity, ... [11] 3-Methylglutaconic aciduria type III (MGCA3) is a neuroophthalmologic syndrome consisting of early-onset bilateral optic atrophy and later-onset spasticity, extrapyramidal dysfunction, and cognitive deficit. [12] What are the main symptoms of 3-Methylglutaconic Aciduria? Symptoms may present in childhood for some affected individuals, while for others symptoms do not appear until early adulthood. The main symptoms include delayed development including motor and speech.

Diagnostic Tests for 3-Methylglutaconic Aciduria Type 3

Diagnosing 3-methylglutaconic aciduria type 3 (MGA3) involves a combination of clinical evaluation and laboratory tests. Here are the diagnostic tests that can be used to confirm the condition:

• Urine Test: A urine test is

Treatment Options for 3-Methylglutaconic Aciduria Type 3

According to the search results, there are limited treatment options available for 3-methylglutaconic aciduria type 3. However, some potential treatments have been identified:

• Low Leucine or Protein Diet: A low leucine or protein diet is advised to manage symptoms of the condition [7].
• Granulocyte Colony-Stimulating Factor (G-CSF): Treatment with G-CSF seems to be successful and safe in managing the condition, although more research is needed to confirm its effectiveness [2].

It's essential to note that there is no specific effective treatment for 3-methylglutaconic aciduria type 3, and management of symptoms is often focused on addressing disease-related comorbidities [12]. Patients may require ongoing medical care and monitoring to manage their condition.

References

• [7] Suggests a low leucine or protein diet as an advised treatment option.
• [2] Reports the use of G-CSF as a potential treatment for 3-methylglutaconic aciduria type 3.
• [12] Highlights the importance of patient-centered management and addressing disease-related comorbidities.

Differential Diagnosis of 3-Methylglutaconic Aciduria Type 3

3-Methylglutaconic aciduria type 3 (MGA3) is a rare genetic disorder that can be challenging to diagnose. The differential diagnosis for MGA3 involves ruling out other conditions that may present with similar symptoms.

Conditions to Consider:

• Costeff Syndrome: This inherited condition also presents with vision loss, delayed development, and movement problems, making it a key differential diagnosis for MGA3 [6].
• OPA3-related disorders: As MGA3 is caused by mutations in the OPA3 gene, other conditions related to this gene should be considered in the differential diagnosis [2].
• Urea cycle disorders: Conditions like carbamoyl phosphate synthetase I deficiency can present with similar symptoms and require exclusion in the diagnostic process [9].

Diagnostic Approach:

The diagnosis of MGA3 typically involves a combination of clinical evaluation, genetic testing, and biochemical analysis. The presence of increased levels of 3-methylglutaconic acid in urine is a key indicator of this condition [4]. However, specific diagnosis of MGA type IV requires exclusion of all other types of 3-MGA-uria, including Type I, which arises from a defect in the enzyme 3-methylglutaconyl-CoA hydratase [7].

Key Points to Consider:

• Vision problems, movement difficulties, and mild to moderate intellectual disability are common symptoms of MGA3 [3].
• The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the condition [3].

References:

[1] Clinical features of 3-Methylglutaconic aciduria type 3 include abnormality of the eye and genitourinary system. [2] A clinical resource with information about MGA3 and its clinical features, OPA3, is available for reference. [3] The symptoms of MGA3 include vision problems, movement problems, and mild to moderate intellectual disability. [4] 3-methylglutaconyl-CoA hydratase deficiency can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine. [5] Urinary organic acid analysis is essential for differential diagnosis of MGA-uria syndromes. [6] Costeff syndrome is an inherited condition characterized by vision loss, delayed development, and movement problems. [7] There are five recognized types of 3-MGA-uria, including Type I and Type IV. [8] Specific diagnosis of MGA type IV requires exclusion of all other types of 3-MGA-uria. [9] Carbamoyl phosphate synthetase I deficiency is an important differential diagnosis in the encephalopathic neonate.