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Sandhoff Disease
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GM2 Gangliosidosis
Type II, Hexosaminidase Deficiency
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WHAT: Sandhoff
disease is a rare, genetic disease. In this disease, there
is a defect in a cellular enzyme that normally helps break down
certain fatty products (called sphingolipids).
Since the enzyme is defective, these fatty products
don’t get broken down and start building up in the body instead. This
is very damaging to cells in the body, especially in the
brain. There are different types of Sandhoff disease, depending on the age
in which the signs and symptoms start occurring. These types are called
infantile-onset, juvenile-onset, and adult onset. The information here
focuses on the infantile-onset type which starts during early infancy.
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WHO: Sandhoff
disease occurs in about one in 300,000 live births in the US & Canada. The prevalence varies in other countries. Sandhoff
disease is medically similar to Tay-Sachs
disease, another disease involving a defective cellular enzyme, which frequently occurs in
individuals with an Ashkenazi Jewish heritage. However, Sandhoff disease
has a higher incidence rate in non-Jewish populations compared to Tay-Sachs disease, and occurs in many different ethnic
groups. Sandhoff disease occurs in both males and females.
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SIGNS &
SYMPTOMS: Around the age of 4 to 6 months,
infants may start to regress in their development and to show other signs
and symptoms of Sandhoff disease as listed below:
• increasing
mental and motor deterioration. The infant begins to decrease alertness and
interest in
surroundings and loses previously attained
movement skills.
• motor
weakness. The infant’s muscles may become weak and movements may be
difficult
• seizures convulsions of the body
• myoclonus:
shock-like contractions of the muscles
• startled reactions to sound
• difficulty with swallowing
• frequent respiratory infections
• macrocephaly:
the head size may be increased
• doll-like facial appearance: the
amount of facial expressions may be limited
• cherry-red spots in the back of the
eyes (an eye specialist may find this when examining the eyes)
• early blindness
• problems with the heart, spleen, and
liver
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POSSIBLE
CAUSES: Lysosomes are small
sacs in our cells that contain enzymes. These enzymes help break down material in the
cell. In Sandhoff disease, there is a gene abnormality that causes one of these lysosomal enzymes
to be defective. The name of the defective enzyme is called hexosaminidase.
Hexosaminidase normally helps break down a type
of fatty product called sphingolipids. Since hexosaminidase is defective in Sandhoff disease, the sphingolipids are not broken down properly and start
building up in the cells, especially in cells of the brain. Buildup of these
lipids is toxic to cells in the body and can cause cellular
dysfunction. As cells get unhealthy and degenerated, the signs and symptoms of
Sandhoff disease start showing.
Sandhoff disease is an autosomal recessive genetic disease. This means that affected
individuals have two defective copies of the hexosaminidase
gene, one inherited from each parent. The
parents both have one normal copy and one defective copy, so they are not
affected. The parents should know that their affected children just
happened to receive two defective copies by random chance, and it is not
their fault in any way.
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DIAGNOSIS: Sandhoff
disease is diagnosed based on the signs and symptoms it causes and based on
lab tests. Symptoms such as muscle weakness and developmental problems can
be caused by different neurological and muscle diseases, so the lab tests
help doctors figure out which disease is causing the symptoms. Since the hexosaminidase enzyme is defective in Sandhoff disease,
there is a special blood test that measures how the hexosaminidase
enzyme is working. The results of this
blood test help distinguish Sandhoff disease from other genetic diseases of cellular metabolism
like Tay-Sachs disease.
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TREATMENT: Currently
there is no cure for Sandhoff disease, and the treatment is mostly
supportive treatment for the child. This may include medications to
decrease seizures and muscle contractions (myoclonus), medications to treat respiratory
infections, and a special diet for feeding difficulties.
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PROGNOSIS: Unfortunately,
a cure for Sandhoff disease has not yet been found, and children with the
infantile-type of this disease have survived in the past to about 3 to 4
years of age. However, there are many studies of Sandhoff disease that are
being done. Researchers are trying to find medications to stop the fatty
products from building up in the cells, especially those in the brain. They
are also trying to find medications to prevent the fatty products from
being made in the first place. Other newer studies are focusing on
decreasing inflammation in the brain to try to increase the number of
healthy brain cells. Hopefully, helpful medications will
be found through these studies.
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