Beta-Mannosidosis

Beta-Mannosidosis is a rare genetic disorder that affects various parts of the body.

Beta-mannosidosis (β-mannosidosis) is an extremely rare genetic disease that belongs to a larger group of lysosomal storage disorders. Lysosomal storage disorders are characterized by metabolic abnormalities that cause a build-up of various toxic materials in the lysosomal compartment of cells throughout the body. The signs and symptoms of beta-mannosidosis vary in both the severity and age of onset. Almost all affected individuals experience some degree of intellectual disability, and some have delayed motor development. Other signs and symptoms can include muscle abnormalities, seizures, speech and hearing difficulties, reduced sensations in extremities, repeat ear and respiratory infections, unique facial features, and behavioral and psychiatric challenges. Beta-mannosidosis is caused by changes (variants or mutations) in the MANBA gene and is typically inherited in an autosomal recessive pattern.[rx]

Types of Beta-Mannosidosis:

Beta-Mannosidosis has two main types:

1. Juvenile-Onset Beta-Mannosidosis: This type of Beta-Mannosidosis typically appears in childhood or adolescence. Symptoms tend to become more severe as the affected individual grows older.
2. Adult-Onset Beta-Mannosidosis: Adult-onset Beta-Mannosidosis may not become apparent until adulthood. Symptoms may develop slowly and progress at a milder pace compared to the juvenile-onset type.

Causes of Beta-Mannosidosis:

Beta-Mannosidosis is caused by mutations in the MANBA gene. This gene provides instructions for making an enzyme called beta-mannosidase, which is essential for breaking down certain complex sugars in the body. When the MANBA gene is mutated, the enzyme doesn’t work correctly, leading to the accumulation of harmful substances in various tissues.

Beta-mannosidosis is caused by changes (variants or mutations) in the MANBA gene. The MANBA gene contains instructions for creating a type of protein (enzyme) called beta-mannosidase. Inside cells throughout the body are specialized compartments called lysosomes that contain enzymes to break down (metabolize) and recycle materials to support normal body functions. One type of material is glycoproteins that are composed of chains of sugar molecules (oligosaccharides). During metabolism, the chain is taken apart by separating the sugar molecules. Beta-mannosidase helps this process in certain oligosaccharides that contain a particular sugar molecule called mannose. The enzyme’s function is to specifically separate mannose from its neighboring sugar molecule and help break down the chain.[rx]

Individuals affected by beta-mannosidosis have a variant of the MANBA gene that causes insufficient beta-mannosidase enzyme activity. Mannose-containing oligosaccharides cannot be completely metabolized and instead abnormally accumulate in the cell. This progressive accumulation can cause toxicity in the cell and leads to the dysfunction of various tissues and organs of the body.[rx]

Beta-mannosidosis is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits a mutated gene from each parent. If an individual receives one normal gene and one mutated gene for the disease, the person will be a carrier for the disease, but will not show symptoms. The risk for two carrier parents to both pass the mutated gene and have an affected child is 25% with each pregnancy. The risk of having a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.[rx]

Symptoms of Beta-Mannosidosis:

Beta-Mannosidosis can manifest a range of symptoms. Keep in mind that not all individuals with this condition will experience all these symptoms, and the severity can vary. Here are 20 common symptoms:

1. Developmental delays in children.
2. Intellectual disability.
3. Behavioral problems.
4. Slow growth.
5. Coarse facial features.
6. Enlarged liver and spleen.
7. Bone abnormalities.
8. Joint stiffness.
9. Frequent infections.
10. Hearing loss.
11. Vision problems.
12. Recurrent respiratory infections.
13. Abnormal gait.
14. Muscle weakness.
15. Abdominal pain.
16. Heart problems.
17. Difficulty speaking.
18. Seizures.
19. Loss of coordination.
20. Short stature.

Diagnostic Tests for Beta-Mannosidosis:

Diagnosing Beta-Mannosidosis often involves a combination of clinical evaluations and laboratory tests. Here are 20 diagnostic tests and methods used:

1. Physical examination to assess physical and developmental signs.
2. Blood tests to measure enzyme levels.
3. Urine tests to detect abnormal substances.
4. Genetic testing to identify mutations in the MANBA gene.
5. X-rays to evaluate bone abnormalities.
6. MRI scans for assessing brain and spinal cord abnormalities.
7. Hearing tests to check for hearing loss.
8. Vision tests to assess visual impairments.
9. Biopsy of affected tissues for further analysis.
10. Echocardiogram to examine heart function.
11. Electroencephalogram (EEG) to detect seizures.
12. Lumbar puncture (spinal tap) to evaluate cerebrospinal fluid.
13. Skeletal survey to assess bone abnormalities.
14. Audiometry for detailed hearing assessments.
15. Ophthalmologic examination for eye-related issues.
16. Electromyography (EMG) to evaluate muscle function.
17. Genetic counseling to understand the risk of passing on the condition.
18. Neuropsychological assessments for cognitive function.
19. Endoscopy to examine digestive tract issues.
20. Molecular analysis to study genetic mutations in-depth.

A blood test to measure beta-mannosidase enzyme activity in blood plasma or white blood cells (leukocytes) can reveal less activity than expected. A urine test (urinalysis) can show a higher amount of mannose-containing oligosaccharides in the urine. A diagnosis of beta-mannosidosis can be confirmed with molecular genetic testing.[rx]

Molecular genetic testing can detect variants in the MANBA gene but is available only as a diagnostic service at specialized laboratories. More recently, the MANBA gene has been added to some molecular genetic test panels for lysosomal storage disorders. These panels examine genes found throughout the genome that have known associations with lysosomal storage disorders.[rx] A blood or saliva sample can be used for this testing. This more targeted approach means the test can be less expensive. However, if no variant is found using this targeted approach, a molecular genetic test called whole exome sequencing (WES) might be recommended, either in the patient only or as a trio test including the parents. WES examines the parts of genes that provide instructions to create proteins called exons and evaluates all the exons (exome) at the same time. WES can detect variants in the MANBA gene that may have gone undetected by the panel test but also identifies variants in other genes that cause similar clinical features.[rx]

Treatment Options for Beta-Mannosidosis:

While there is no cure for Beta-Mannosidosis, various treatment approaches aim to manage symptoms and improve the quality of life. Here are 30 treatment options:

1. Supportive care to address specific symptoms.
2. Physical therapy to improve mobility and muscle strength.
3. Occupational therapy for daily life skills.
4. Speech therapy to assist with communication difficulties.
5. Behavioral therapy for managing emotional and behavioral issues.
6. Growth hormone therapy to promote growth in children.
7. Orthopedic interventions to manage bone abnormalities.
8. Hearing aids or cochlear implants for hearing loss.
9. Visual aids and adaptive devices for vision problems.
10. Medications to manage seizures.
11. Pain management strategies.
12. Enzyme replacement therapy (ERT) in research stages.
13. Anti-inflammatory medications for joint pain.
14. Antibiotics to treat recurrent infections.
15. Cardiac medications for heart-related issues.
16. Respiratory support as needed.
17. Nutritional support for those with feeding difficulties.
18. Splints or braces for joint stiffness.
19. Regular follow-up with specialists.
20. Psychological support for individuals and families.
21. Dietary modifications to address swallowing problems.
22. Assistive communication devices for speech difficulties.
23. Oxygen therapy for respiratory issues.
24. Gastrointestinal medications for digestive problems.
25. Antioxidant supplements for overall health.
26. Mobility aids like wheelchairs or walkers.
27. Pain-relieving creams or gels.
28. Sleep therapy for sleep disturbances.
29. Genetic counseling for family planning.
30. Participation in clinical trials for experimental treatments.

Drugs for Beta-Mannosidosis:

Currently, there are no specific drugs approved for the treatment of Beta-Mannosidosis. However, researchers are actively exploring potential therapies. Some drugs that may be considered for symptom management include:

1. Pain relievers for joint and muscle pain.
2. Antibiotics to treat infections.
3. Anti-seizure medications for individuals with seizures.
4. Anti-inflammatory drugs for joint inflammation.
5. Cardiac medications for heart-related issues.
6. Nutritional supplements to support overall health.
7. Enzyme replacement therapy (ERT) in experimental stages.
8. Antioxidant supplements for cellular health.

In Conclusion:

Beta-Mannosidosis is a complex genetic disorder with various symptoms that can affect different aspects of a person’s life. Although there is no cure, a multidisciplinary approach involving medical, therapeutic, and supportive interventions can help manage symptoms and improve the quality of life for individuals with Beta-Mannosidosis. Genetic counseling can also assist families in understanding the condition’s inheritance pattern. Research into potential treatments continues, offering hope for the future.

 

Disclaimer: Each person’s journey is unique, treatment plan, life style, food habit, hormonal condition, immune system, chronic disease condition, previous medical  history is also unique. So always seek the best advice from a qualified medical professional or health care provider before trying any treatments to ensure to find out the best plan for you. This guide is for general information and educational purposes only. If you or someone are suffering from this disease condition bookmark this website or share with someone who might find it useful! Boost your knowledge and stay ahead in your health journey. Thank you for giving your valuable time to read the article.

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