Introduction:
Gangliosidoses is a set of inherited metabolic diseases characterized by a lack of the various proteins required to break down lipids. Lipids, which include fatty compounds such as oils, waxes, steroids, and other substances, are crucial components of the membranes found inside and between cells and the myelin sheath that covers and shields the nerves.
Unusual lipid accumulation can result in irreversible damage to cells and tissues in the brain and neurological systems, particularly nerve cells and other body parts (including the liver and spleen). Two separate classes of gangliosidoses can have an equivalent impact on both sexes. They are GM1 gangliosidosis and GM2 gangliosidosis.
What Is GM2 Gangliosidosis?
GM2 gangliosidosis is a rare hereditary condition that gradually damages the brain and spinal cord nerve cells. The most frequent form of the disease appears in infancy, although other variants might appear in childhood, adolescence, or even adulthood. The condition is one of around 50 illnesses known as lysosomal storage disorders (LSD), in which a genetic mutation impairs lysosomes' regular function in human cells.
There are three forms of GM2 gangliosidosis. They are as follows.
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Tay-Sachs disease.
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Sandhoff disease.
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AB variant.
How Are They Inherited?
This disorder is inherited in an autosomal recessive fashion, which means that both copies of the gene in each cell are mutated. Therefore, each parent of a person with an autosomal recessive disorder carries one copy of the defective gene, although usually, neither parent exhibits the disease's signs and symptoms.
What Are Tay-Sachs Disease and Its Causes and Symptoms?
Tay-Sachs disease is a rare genetic illness handed down from generation to generation. Tay-Sachs is categorized into infantile, juvenile, and adult types depending on the symptoms and when they initially manifest. The infantile variant of Tay-Sachs is the most common. In this kind, the baby's nerve damage typically starts while still in the womb. Symptoms usually begin to show between the ages of three and six months. The sickness progresses rapidly, and the child dies by age of four or five. Adults with late-onset Tay-Sachs disease are incredibly uncommon.
Causes:
A deficiency of hexosaminidase A in the body causes Tay-Sachs disease. This protein aids in the breakdown of gangliosides, a type of chemical present in nerve tissue. Without this protein, gangliosides, especially ganglioside GM2, accumulate in cells, frequently in brain nerve cells. A gene defect on chromosome 15 causes Tay-Sachs disease.
Symptoms:
Any of the following signs could be present:
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Loss of eye contact and blindness.
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A loss of muscle tone and strength, a decline in motor function, and paralysis.
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Slow development and lagging social and cognitive abilities.
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Dementia (loss of brain function).
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Heightened startle response.
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Irritability.
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Listlessness.
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Seizures.
What Are Sandhoff Disease and Its Causes and Symptoms?
Sandhoff disease is a rare genetic condition that damages nerve cells (neurons) in the brain and spinal cord over time (central nervous system). Based on the age at which the first indications and symptoms manifest, this disorder is divided into three main types: infantile, juvenile, and adult.
Causes:
Changes in the HEXB gene bring on Sandhoff disease. The body does not produce enough beta-hexosaminidase due to mutations. The body cannot break down some fats without beta-hexosaminidase. The fats accumulate in lethal amounts, especially in the brain and spinal cord nerve cells.
Symptoms:
The classic type of Sandhoff disease affects babies. At birth, they seem healthy, but symptoms start to surface by 3 to 6 months old.
Signs could be the following.
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Abnormal bone growth.
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Awkward moves.
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The eyes have "cherry-red" patches on them.
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Larger internal organs, especially the liver and spleen, or an enlarged head (macrocephaly).
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Exaggerated responses to loud noises (startle response).
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Respiratory infections that recur frequently.
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Motor skills such as crawling, sitting up, and rolling over develop slowly.
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Muscle weakness, ataxia (problems with control), or spasms of the muscles (myoclonus).
Babies typically experience the following as Sandhoff disease progresses:
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Loss of hearing.
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Intellectual impairments.
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Paralysis.
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Loss of vision.
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A quick death.
What Are the AB Variant and Its Causes and Symptoms?
GM2-gangliosidosis, AB variation, is a rare genetic condition that gradually damages nerve cells (neurons) in the brain and spinal cord.
Causes:
Mutations in the GM2A gene inhibit the function of the GM2 ganglioside activator, preventing beta-hexosaminidase A from breaking down GM2 ganglioside. This chemical consequently builds up to dangerous amounts, especially in the neurons of the brain and spinal cord. The gradual degeneration of these neurons brings on the signs and symptoms of the AB variation by the accumulation of GM2 ganglioside.
Symptoms:
- The AB variety exhibits signs and symptoms as early as infancy.
- Infants with this condition often appear normal until the age of three to six months, when their growth slows and the muscles needed for movement weaken.
- Infants that are affected lose their ability to turn over, sit up, and crawl.
- They also acquire an enhanced startle response to loud stimuli.
- Children with the AB variation endure convulsions, vision and hearing loss, intellectual incapacity, and paralysis as the disease worsens.
- An eye exam can reveal a cherry-red spot, an eye irregularity indicative of this condition.
- Children with the AB variant typically live until they are in their early childhood.
How Are They Diagnosed?
Medical professionals use the following factors to diagnose.
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Analyze the symptoms and when they first appeared.
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Discussion about ethnic heritage and family history.
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Physical examination.
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Blood tests to evaluate whether hexosaminidase levels are low or absent.
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Genetic tests to determine if the gene mutation is present.
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Eye examination (a cherry-red patch is visible in the macula).
What Are the Treatment Methods Available for GM2 Gangliosidosis?
GM2 gangliosidosis has no known cure, and no proven treatments can halt the disease's progression. However, some treatments can aid in symptom management and avert problems. Support and comfort are the main aims of treatment.
Supportive Therapies Consist of the Following:
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Medication:
Several prescription drugs are available to treat symptoms and avoid complications, such as anti-seizure or antibiotics for infections.
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Respiratory Treatment:
Too much mucus in the lungs increases the risk of lung infections, making breathing difficult. Exercise, chest physiotherapy (CPT), and other methods can aid in clearing the lungs of mucus. Other methods to lower the risk of mucus buildup and avoid aspiration pneumonia include medications that decrease saliva production and posture strategies.
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Nutrition:
Children may have difficulty swallowing or suffer respiratory problems if they inhale food or fluids into the lungs while eating. A doctor might suggest an assistive feeding device, such as a feeding tube, to avoid those issues.
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Physical Therapy:
A child may benefit from physical therapy as the disease worsens to keep joints flexible and preserve as much range of motion as possible. Physical therapy can lessen or delay joint stiffness and the potential discomfort and loss of function in affected muscles.
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Therapy for Speech and Language:
Therapists specializing in speech and language can help with swallowing issues.
Conclusion:
GM2 gangliosidosis is a disorder due to gene mutation; no proven treatment method exists. However, Studies are being conducted on various treatment methods, such as gene therapy and enzyme replacement therapy, to cure or slow down the disease progression.
