What Is Beta-Mannosidase Deficiency?
Beta-mannosidase deficiency is commonly known as beta-mannosidosis or lysosomal beta-mannosidase deficiency. It is a rare genetic disorder that alters how the body breaks down specific kinds of sugar molecules. Researchers believe this extremely uncommon disorder is an autosomal recessive lysosomal storage disorder (LSD) characterized by a lack of activity of an enzyme called beta-mannosidase.
In lysosomal storage disorders, lysosomes get affected. Lysosomes are the tiny sacs present in the cells that are important for breaking down and recycling substances like fats and carbohydrates. People who suffer from lysosomal storage disorders are either deficient in one of the vital enzymes that are necessary for lysosome action or do not have enough of them to properly break down molecules as is necessary for healthy cellular function.
What Causes Beta-Mannosidase Deficiency?
Beta-mannosidase deficiency is a hereditary disorder known to be caused by MANBA (mannosidase beta) gene mutation. The MANBA gene provides instructions for synthesizing the beta-mannosidase enzyme, and it is responsible for its production. The beta-mannosidase enzyme is found in the lysosomes of cells. It is a very important enzyme because it helps in the breakdown and recycling of particular complex sugars, which contains the sugar molecule mannose.
Due to a genetic mutation in the MANBA gene, the function of beta-mannosidase gets impaired, and this results in an accumulation of complex sugar compounds in cells that eventually leads cells to malfunction. An affected child inherits one defective copy of the MANBA gene from each parent since this genetic disease is inherited in an autosomal recessive way.
What Are the Signs and Symptoms of Beta-Mannosidase Deficiency?
This genetic disorder starts showing symptoms at an early age (infancy) in children. However, in some individuals, the symptoms may appear in adulthood. This rare disorder affects the entire body, including the brain. The symptoms are discussed below.
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Seizures: Seizure is a term used to describe a neurological condition where the individual experiences sudden attacks that last for a few seconds or minutes. These attacks include jerks and trembling of the body or loss of consciousness or strange sensations.
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Hyperactivity: Children having this disorder show hyperactive behavior.
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Peripheral Neuropathy: Peripheral neuropathy occurs as a result of disturbances in the peripheral nervous system. It feels like numbness or tingling sensation in the extremities (hands and feet).
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Difficulty Hearing: Individuals having this disorder may possess congenital deafness (deaf since birth). Hearing impairment is due to a genetic mutation that causes a reduction in the sensory perception of sound.
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Generalized Hypotonia: Beta-mannosidase deficiency causes abnormally low muscular tone in affected individuals. This is called hypotonia. Babies with low muscle tone exhibit poor posture; lifting them makes them appear droopy, have more flexible joints, lack muscular strength, and get tired frequently.
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Delayed Motor Development: Individuals with a beta-mannosidase deficiency show motor delay, a developmental delay marked by a delay in developing motor abilities. For example, delays in achieving age milestones in babies like rolling, crawling, sitting, walking, etc.
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Neurological Speech Impairment: The affected individuals often show speech impairment, and they find difficulty in speaking.
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Dysphagia: Dysphagia is used to describe difficulty in swallowing, which is often seen in individuals with beta-mannosidase deficiency.
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Behavioral Problems: These individuals may show behavioral disturbances such as aggression or impulsivity. An individual with impulsive behavior responds abruptly in response to immediate stimuli. They act instantly without planning or taking results into account; they have difficulty making or sticking to plans, always have a feeling of urgency, and can be engaged in self-harming activities under emotional distress.
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Depression: This disorder can induce symptoms of depression like prolonged periods of emotional upset and sadness, hopelessness and guilt, suicidal thoughts, apprehensions about the future, etc.
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Intellectual Disability: An IQ (intelligence quotient) score of less than 70 has been deemed to indicate intellectual disability, often known as mental retardation. This feature is common in individuals with beta-mannosidase deficiency.
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Psychomotor Developmental Delay: The affected children delay achieving mental milestones like talking, speech, and language and developing cognitive, social, and emotional skills. As a result of this, these children may become extremely introverted.
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Angiokeratomas: The children affected with this rare genetic disorder have spots on their skin that usually appear dark and red. These dark red spots are called angiokeratomas, and they are caused by groups of enlarged blood vessels.
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Frequent Infections: Beta-mannosidase deficiency makes an individual more susceptible to ear and respiratory infections. Therefore, these people get recurrent infections in these areas.
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Facial Features: Individuals with this disorder have unusual facial features.
How Is Beta-Mannosidase Deficiency Diagnosed?
Beta-mannosidase deficiency is diagnosed based on clinical features (signs and symptoms). If the doctor suspects beta-mannosidase deficiency, they usually do a screening test, including urine testing. This test can identify abnormal oligosaccharides, which can hint at this disorder's presence. If the results of this test come in favor of beta-mannosidase deficiency, a confirmation test is conducted. This test includes enzymatic analysis or molecular testing. The positive results of the confirmatory test confirm the presence of beta-mannosidase deficiency.
What Is the Treatment of Beta-Mannosidase Deficiency?
Unfortunately, there is no treatment available for this genetic disorder. Symptomatic treatment is the current state of management for this disorder. Treatment is given to provide relief from the symptoms. For example, antiepileptic drugs can manage seizures, and mental health-related symptoms can be controlled by adhering to a psychiatrist's treatment plan. The respective medicines can manage recurrent ear and respiratory infections. Hence, this disorder can not be cured but controlled with proper treatment plans and medicines.
How Rare Is Beta-Mannosidase Deficiency?
Globally, there have been reports of about 20 affected people. Estimating the precise incidence of beta-mannosidosis is challenging because persons with moderate or vague symptoms may never receive a diagnosis. Since its incidence is so low, there is not much information available on this rare disease. However, researchers are working to explore more about this disorder.
Conclusion:
Beta-mannosidase deficiency is an extremely rare genetic disorder that decreases the quality of life of affected individuals. It affects not only physical health but also affects mental health. However, early diagnosis and treatment in children can improve the quality of life and increase the life expectancy in individuals having this rare disease.
