What Is Sanfilippo Syndrome?
Sanfilippo syndrome is a progressive neurodegenerative disease that primarily affects the brain and the spinal cord. This condition is predominantly genetic and is considered an autosomal recessive disorder. Though this syndrome initially affects the central nervous system, it leads to deterioration in the brain's normal functioning over time. The decreasing brain function causes various health issues associated with other body parts, such as limbs and facial muscle coordination.
People with Sanfilippo syndrome do not show any clinical features at birth, and the signs and symptoms usually develop during early childhood. Sanfilippo syndrome is also known as mucopolysaccharidosis type III or MPS III. There are four subtypes of Sanfilippo syndrome, which are denoted by the letters A, B, C, and D.
Among the four types of Sanfilippo syndrome, type A is the most severe and common type. Type B Sanfilippo syndrome then follows this as the second common subtype. Type C and D are scarce and only account for roughly one case in one million cases of Sanfilippo syndrome. Statistically speaking, Sanfilippo syndrome is a rare condition that affects only one in 70,000 children. It has been commonly reported that the symptoms appear only after three years of age.
Sanfilippo syndrome baby is a child born with a defect in one of the genes responsible for breaking down the heparan sulfate. This work is done by the genes through enzymes. Enzymes are made from the genes.
What Are the Causes of Sanfilippo Syndrome?
There are four subtypes of Sanfilippo syndrome, and they are caused due to either of the following reasons.
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Genetic mutation.
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Genetic defect.
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Genetic variation.
This condition is caused when the body does not break down a complex sugar molecule called heparan sulfate, which is a part of the glycosaminoglycans (GAG). The body usually produces heparan sulfate, and then it is broken down with the help of the metabolic processes to help regulate regular body functioning, such as:
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Repair of the wound.
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Cell growth.
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Cartilage repair and growth.
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Cell signaling.
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Clotting of blood.
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Connective tissue growth.
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Building of nerve tissues.
Hence, if the body is not breaking down heparan sulfate in sufficient quantity, the level of heparan sulfate accumulates, which leads to the following:
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Organ damage.
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Delay in neurological development.
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Changes in behaviors.
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Problems in growth.
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Neurological deterioration.
The four subtypes of Sanfilippo syndrome are caused due to a deficiency or a mutation of four different types of enzymes responsible for breaking down heparan sulfate. The genes that are responsible for each subtype of Sanfilippo syndrome or MPS are
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SGSH gene, in MPS III-A.
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NAGLU gene, in MPS III-B.
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HGSNAT gene, in MPS III-C.
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GNS gene, in MPS III-D.
Inheritance:
This condition is an autosomal recessive pattern. It means both gene copies are present in the cells and have variants. The parents of those individuals with an autosomal recessive gene carry one copy of an altered gene. These individuals do not exhibit any symptoms.
Frequency:
The most common condition is MPS III, considered the most common form of mucopolysaccharidosis. It is estimated to affect one in seventy thousand people among all the types of MPS III. MPS IIIA and MPS IIIB are considered more common than MPS IIIC and MPS IIID.
What Are the Symptoms of Sanfilippo Syndrome?
Although Sanfilippo syndrome is a genetic condition (meaning children are born with this condition), symptoms usually begin to exhibit only when the child is at least two years old. Some of the typical early signs of Sanfilippo syndrome include
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Hyperactivity or compulsive disorders.
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Trouble sleeping.
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Developmental delays.
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Stiff joints.
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Trouble or difficulty in speaking.
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Coordination issues result in mobility issues.
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Heavy elbows or abnormal head size.
These are some of the early symptoms, and they become worse as the child gets older. The severity of the symptoms differs from one person to another based on the rate of progression of the disease. Based on research involving individuals affected by Sanfilippo syndrome, healthcare professionals have classified three stages of developmental issues.
They are,
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Stage 1: Between the ages of one and three, the child will have delayed cognitive development. Also, there will be frequent infections of the eyes, nose, throat, or ears.
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Stage 2: When the child is between the ages of three to five, behavioral changes such as difficulty sleeping and a decline in cognitive development occur. Stage 2 continues until the child is 13 to 15 years of age.
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Stage 3: The final stage includes regression of fundamental motor skills and cognitive functions. During this stage, the child might start losing language skills and continue to have other physical issues, such as breathing troubles or seizures.
How Is Sanfilippo Syndrome Diagnosed?
It is highly crucial to diagnose Sanfilippo syndrome early during childhood to provide the child with the necessary support. The doctor first performs a physical examination, and if he suspects Sanfilippo syndrome, the doctor will recommend the following tests to help diagnose the disease effectively. They are:
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Blood test.
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Urine test.
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Supplemental newborn screening.
The first step involves the urine MPS test, specifically designed to identify GAGs and heparan sulfate levels. If this test produces a positive result (increased level of heparin sulfate), then a blood enzyme test is done to reconfirm the result. The blood test will have a more accurate finding of which enzyme cannot break down the heparan sulfate and hence help find the type of Sanfilippo syndrome.
The genetic test includes providing blood or saliva samples to screen for any genetic mutations or variations associated with Sanfilippo syndrome. Another non-official way of detecting Sanfilippo syndrome is a supplemental screening of a baby under the age of one.
How Is Sanfilippo Syndrome Treated?
At present, there is no apparent cure for Sanfilippo syndrome. However, there have been many clinical and research trials involving stem cell research and animal trials for treating Sanfilippo syndrome. These trials include:
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Gene therapy.
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Enzyme replacement therapy (ERT).
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Substrate reduction therapy (SRT).
Gene therapy and ERT have been more promising in managing the condition of these three. Even if these options do not cure the disease permanently, they are an efficient way to help manage most of the symptoms and improve the quality of the individual affected by Sanfilippo syndrome. They help stabilize the situation, but more research and human trials are still required to make this a viable treatment option.
Conclusion
Sanfilippo syndrome is a severe health condition, and it reduces the life expectancy of the affected person by up to 10 to 20 years. Many research and clinical trials are conducted by the government and pharma companies in the hope of finding a cure. However, in the meantime, there are still options for managing some of the severe symptoms and improving the quality of life of the affected person, but it is essential to get early treatment. Hence, it is vital to reach out to the doctor as soon as possible if one notices any of the symptoms in the child.
