Introduction
Sandhoff disease is a rare sporadic hereditary disorder that commonly occurs in infancy, but can also appear in young children and adults. The neuron cells of the central and peripheral nervous system are destroyed by the disease. Deficiency of the enzyme beta-hexosaminidase causes the development of this disease. Sandhoff disease is a type of lysosomal storage disease. Lysosomes are present in almost every cell of the body and have plenty of enzymes that help to break down and digest molecules. People suffering from this disease lack the enzyme beta-hexosaminidase, due to which excessive fats are accumulated in the cells, causing damage to the brain and other organs of the body, sometimes causing death in the initial childhood days. In other words, it is a severe form of another neurological disease, Tay-Sachs disease.
What Is the Epidemiology of Sandhoff Disease?
Sandhoff disease is a sporadic disease. It usually occurs in one child in every 1 million people. Sandhoff disease is a genetic disorder. It can be passed through several generations. The disease is more commonly seen in people with particular ethnic origins. The disease is present in specific populations only. So, the predisposing factors for Tay-Sachs disease include the populations of
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Jewish communities (Ashkenazi Jews) in Central Europe.
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Metis Indo-Canadian people.
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People of Eastern Europe.
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Lebanese people.
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North Argentina people.
What Causes Sandhoff Disease?
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Genetic mutations occur in the HEXB gene.
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The HEXB gene is mainly responsible for providing instructions to synthesize a protein that is crucial for the nervous system. This gene is part of the two enzymes, beta-hexosaminidase A and beta-hexosaminidase B.
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Mutation in the HEXB gene disrupts the enzymatic activity that prevents the breakdown of certain toxic substances called gangliosides.
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The gangliosides are accumulated in the brain and spinal cord, thereafter causing damage to the neurons and degeneration of the nerve fibers.
How Is Sandhoff Disease Classified?
The disease is classified into three forms.
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Classic or infantile type.
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Juvenile type.
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Adult type.
Infantile Type - It is the most common type of disease. It appears in infants and is the most severe type of disease. The infants appear normal up to the age of four to six months. Gradually, the symptoms start developing with the weakening of the muscles and poor growth development. Motor skill development is also poor. The children affected by this disease live until early childhood.
Juvenile Type - It is a rare form of the disease. The signs and clinical symptoms of this form of the disease are mild as compared to the classic (infantile) form. It usually appears in children between the ages of two to eleven years. This type is characterized by cognitive impairment, seizures, and cerebral ataxia (impaired muscle coordination), along with speech difficulties.
Adult Type- It is also a very rare form of the disease. Here, the clinical signs and symptoms are less severe than the infantile type. However, the symptoms vary a lot. The adults affected by this disease show signs of impaired movement and psychological problems, along with a lack of coordination.
What Are the Signs and Symptoms of Sandhoff Disease?
The clinical signs and symptoms vary according to the age at which the disease is occurring. The classical signs of the disease include:
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Poor development of facial features.
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Poor development of the bones.
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Impaired movement, making it difficult to walk.
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Loss of motor skills in babies, such as sitting, crawling, and turning over.
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A distinctive feature, the “cherry-red” spot on the eyeball, is characteristic of the infantile form. It is usually identified on eye examination.
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The head is enlarged (macrocephaly).
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The internal organs are also enlarged (organomegaly), in particular, the liver and spleen.
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Startled response to loud noises.
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Respiratory (breathing) infections occur frequently.
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Speech difficulties.
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Impaired muscle coordination (cerebral ataxia).
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Frequent twitching of muscles (myoclonus).
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Weakened muscles.
As the Sandhoff disease worsens, children may begin to experience:
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Hearing impairment.
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Difficulty in vision, sometimes leading to blindness.
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Mental retardation.
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Paralytic attack.
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Frequent seizures.
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Difficulty standing.
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Difficult breathing
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Early death.
When the disease appears in later stages of life, the symptoms do appear but are mild and less severe. Adults may even develop psychiatric problems.
How Is the Diagnosis of Sandhoff Disease Made?
The disease is usually diagnosed by the healthcare professional by thoroughly examining the patient.
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Extensive physical examination includes reviewing the symptoms and the age at which the symptoms appeared first.
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It is important to determine the family history and ethnic origin of the patient to confirm the disease.
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Hematological (blood) tests are carried out to evaluate the activity of beta-hexosaminidase enzymes. The enzymatic activity will be either low, reduced, or absent.
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Genetic testing can be carried out to see if the genetic mutation is present or not. This is done to confirm the diagnosis.
What Is the Management of Sandhoff Disease?
There is no definitive treatment for Sandhoff's disease. Treatment is generally aimed at reducing the signs and symptoms of the diseases. The aim of the therapy is to comfort the child.
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Anticonvulsant drugs may be given to manage seizures.
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Provide a balanced diet and healthy nutrition.
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Keeping the child hydrated.
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Maintaining the patency of the airways.
Genetic counseling of the families affected by Sandhoff's disease should be done to make them aware of the disease outcome. Couples who suffer from a familial risk of this disease should consult a doctor before planning for pregnancy. So, a health expert should be consulted before planning for pregnancy.
What Is the Prognosis of the People with Sandhoff Disease?
Sandhoff disease has a poor prognosis. The people and children affected by the disease have a very short span of life. Infants usually affected by the disease die as early as by the age of four years due to severe complications such as respiratory infections.
Conclusion
Sandhoff disease is a rare genetic lysosomal storage disorder. It is characterized by the deposition of toxic levels of excessive gangliosides in the neurons of the brain and spinal cord. Prevention of the condition is not possible. Affected babies have severe complications leading to early death. Genetic counseling should be given to the family members, and treatment should be aimed at minimizing the symptoms of the children. However, more research is required to unravel the potential treatment for Sandhoff disease.
