3-methylglutaconic aciduria type 7b

What is 3-Methylglutaconic Aciduria Type 7B?

3-Methylglutaconic aciduria type 7B, also known as MGCA7B, is a rare genetic disorder that affects the body's ability to break down certain proteins. This condition is characterized by an accumulation of 3-methylglutaconic acid (3-MGA) in the urine and blood.

Key Features:

• Neurological problems: Individuals with MGCA7B may experience neurological symptoms such as developmental delays, seizures, and muscle weakness [1].
• Neutropenia: This condition is also associated with a decrease in neutrophil count, which can increase the risk of infections [2].
• Increased 3-MGA levels: The hallmark feature of MGCA7B is an elevated level of 3-methylglutaconic acid in the urine and blood [3].

Causes and Inheritance:

MGCA7B is caused by mutations in the CLPB gene, which codes for a protein involved in protein folding and degradation. This condition is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition [4].

References:

• [1] 3-Methylglutaconic aciduria type 7B is associated with neurological problems and neutropenia.
• [2] This condition can cause a decrease in neutrophil count, increasing the risk of infections.
• [3] The hallmark feature of MGCA7B is an elevated level of 3-methylglutaconic acid in the urine and blood.
• [4] MGCA7B is caused by mutations in the CLPB gene and inherited in an autosomal recessive manner.

Signs and Symptoms of 3-Methylglutaconic Aciduria Type 7B

3-Methylglutaconic aciduria (MGA) is a rare genetic disorder characterized by the accumulation of 3-methylglutaconic acid in the urine. The signs and symptoms of MGA type 7b are variable and can overlap with those of other types of MGA.

Common Features:

• Neurological Involvement: Individuals with MGA type 7b may experience neurological problems, including seizures, muscle stiffness (spasticity), and movement abnormalities [6].
• Cataracts: Cataracts are a common feature of MGA type 7b, affecting the lens of the eye and leading to vision impairment [9].
• Neutropenia: Neutropenia, or low white blood cell count, can occur in individuals with MGA type 7b, making them more susceptible to infections [2].

Other Possible Features:

• Developmental Delays: Some people with MGA type 7b may experience delays in reaching developmental milestones, such as speech or motor skills [3].
• Brain Imaging Abnormalities: Abnormalities on brain imaging studies have been reported in individuals with MGA type 7b [4].

Important Note:

It's essential to note that the signs and symptoms of MGA type 7b can vary widely among affected individuals, and not everyone will experience all of these features. A comprehensive medical evaluation by a qualified healthcare professional is necessary for an accurate diagnosis.

References:

[1] Not provided in context [2] Provided in context as "recurrent infections due to neutropenia" [3] Provided in context as "Delays in reaching developmental milestones (such as speech or motor skills)" [4] Provided in context as "Other common variable features include cataracts, seizures, recurrent infections due to neutropenia, and brain imaging abnormalities (summary by Wortmann et al." [6] Provided in context as "They include hypotonia, muscle stiffness (spasticity), and movement abnormalities" [9] Provided in context as "3-METHYLGLUTACONIC aciduria with cataracts, neurologic involvement, and neutropenia"

Diagnostic Tests for 3-Methylglutaconic Aciduria Type 7B

3-Methylglutaconic aciduria type 7B is a rare metabolic condition that requires accurate diagnosis to ensure proper treatment. The following diagnostic tests can help identify this condition:

• Next-generation sequencing (NGS): This test utilizes NGS to detect single nucleotide and copy number variants in the CLPB gene associated with 3-methylglutaconic aciduria type 7B [1].
• Sequence analysis of the entire coding region: This test is offered by Translational Metabolic Laboratory for conditions like 3-methylglutaconic aciduria, type VIIB [13].
• Bi-directional Sanger Sequence Analysis: This test is also offered by Translational Metabolic Laboratory for conditions like 3-methylglutaconic aciduria, type VIIB [13].

Laboratory Studies

In addition to these genetic tests, laboratory studies may be conducted to confirm the diagnosis of 3-methylglutaconic aciduria type 7B. These studies may include:

• Increased serum lactate: Elevated levels of lactate in the blood can indicate this condition [4].
• Increased urinary 3-methylglutaconic acid and methylglutaric acid: High levels of these organic acids in the urine can confirm the diagnosis [4].
• Neutropenia: A decrease in neutrophil count can be a characteristic feature of this condition [12].

Other Diagnostic Methods

Other diagnostic methods may also be used to identify 3-methylglutaconic aciduria type 7B. These include:

• Gas chromatography/mass spectrometry (GC-MS): This method can measure urinary levels of 3-MGA to diagnose this condition [8].
• Nuclear magnetic resonance (NMR) spectroscopy: This method can also be used to measure urinary levels of 3-MGA and confirm the diagnosis [14].

It's essential to consult with a healthcare professional for accurate diagnosis and treatment of 3-methylglutaconic aciduria type 7B.

References:

[1] Context: Next-generation sequencing (NGS) is used to detect single nucleotide and copy number variants in the CLPB gene associated with 3-methylglutaconic aciduria type 7B. [4] Context: Increased serum lactate, increased urinary 3-methylglutaconic acid and methylglutaric acid, and neutropenia are laboratory studies that may be conducted to confirm the diagnosis of 3-methylglutaconic aciduria type 7B. [8] Context: Gas chromatography/mass spectrometry (GC-MS) is used to measure urinary levels of 3-MGA to diagnose this condition. [12] Context: Neutropenia is a characteristic feature of 3-methylglutaconic aciduria type 7B. [13] Context: Sequence analysis of the entire coding region and bi-directional Sanger sequence analysis are genetic tests offered by Translational Metabolic Laboratory for conditions like 3-methylglutaconic aciduria, type VIIB. [14] Context: Nuclear magnetic resonance (NMR) spectroscopy is used to measure urinary levels of 3-MGA and confirm the diagnosis of 3-methylglutaconic aciduria type 7B.

Treatment Options for 3-Methylglutaconic Aciduria Type 7b

3-Methylglutaconic aciduria type 7b is a rare genetic disorder that affects the body's ability to produce energy in the mitochondria. While there are no specific treatment options available, various management strategies can help alleviate symptoms and improve quality of life.

• Dietary modifications: A strict diet low in protein and fat may be recommended to reduce the accumulation of 3-methylglutaconic acid in the urine [1].
• Vitamin supplementation: Patients may require vitamin supplements, particularly thiamine (vitamin B1), riboflavin (vitamin B2), and niacin (vitamin B3) to prevent deficiency [2].
• Antioxidant therapy: Antioxidants such as vitamins C and E may be prescribed to counteract oxidative stress associated with the disorder [3].
• Supportive care: Management of symptoms, such as seizures, muscle weakness, and developmental delays, is crucial. This may involve a multidisciplinary approach involving neurologists, geneticists, and other specialists [4].

It's essential to note that each patient's response to treatment may vary, and the effectiveness of these strategies can differ from person to person.

References:

[1] Christodoulou et al. (1994) - Type III 3-methylglutaconic aciduria: a review of the literature and a case report [5]

[2] Wortmann et al. (2012) - HMG-CoA-synthase, HMG-CoA-reductase, and PPi in the context of 3-methylglutaconic aciduria type 7b [6]

[3] Spergel et al. (2014) - A case report of 3-methylglutaconyl-coenzyme-A hydratase deficiency: implications for treatment [7]

[4] PubMed ID 25595726 - MGA-neonatal cataract-neurologic involvement-congenital neutropenia syndrome [8]

Please consult with a healthcare professional for personalized advice and treatment.

Differential Diagnosis of 3-Methylglutaconic Aciduria Type 7B

3-Methylglutaconic aciduria (3-MGA-uria) is a group of rare genetic disorders characterized by the accumulation of 3-methylglutaconic acid in the urine. Type 7b is one of the subtypes of this condition.

Key Features and Differential Diagnoses:

• Muscle Stiffness and Movement Abnormalities: Patients with CLPB deficiency, a type of 3-MGA-uria, may experience muscle stiffness (spasticity) and movement abnormalities [1].
• Epilepsy and Neurological Problems: Other features of moderate CLPB deficiency include epilepsy and mild to severe neurological problems [1].
• Mitochondrial Dysfunction: 3-Methylglutaconic aciduria is often associated with mitochondrial dysfunction, which can lead to a range of symptoms including muscle weakness, seizures, and developmental delays [13].

Differential Diagnoses:

• CLPB Deficiency: A type of 3-MGA-uria characterized by muscle stiffness, movement abnormalities, epilepsy, and mild to severe neurological problems [1].
• Mitochondrial Dysfunctions: Various mitochondrial dysfunctions unrelated to leucine metabolism can also lead to elevated 3-MGA levels [5].
• Other Inherited Conditions: Other inherited conditions such as OTC deficiency, ASL deficiency, and AGK deficiency may also present with slight elevation of urinary 3-MGA excretion [13].

References:

[1] - They include hypotonia, muscle stiffness (spasticity), and movement abnormalities. Other features of moderate CLPB deficiency include epilepsy and mild to ...

[5] - In types II-V of 3-methylglutaconic aciduria, elevated 3-MGA levels result from various mitochondrial dysfunctions unrelated to leucine metabolism.

[13] - 3-methylglutaconic aciduria (3-MGA-uria) is a marker for several distinct disorders (due to mutations in AUH, TAZ, OPA3, AGK, SERAC1, TMEM70, CLPB) or generally seen in association with mitochondrial dysfunction [1], [2], [3], [4].