Sanfilippo Syndrome – Causes, Symptoms & Treatment


Sanfilippo syndrome is a congenital metabolic disease that occurs very rarely. It is one of the mucopolysaccharidoses.

What is Sanfilippo Syndrome?

Sanfilippo syndrome is a disease of glycosaminoglycan metabolism that is inherited in an autosomal recessive manner. The disease is also called mucopolysaccharidosis type III and belongs to the group of mucopolysaccharidoses.

Depending on the gene defect in Sanfilippo syndrome, doctors distinguish between the four subtypes A to D. Sanfilippo syndrome occurs only very rarely. Its frequency is 1:60,000. When the affected child is born, there are no noticeable symptoms. Mucopolysaccharidosis becomes noticeable between the ages of three and four through very restless and aggressive behavior and delayed mental development .

From the second decade of life, in addition to the behavioral disorders of the patient , spastic paralysis becomes apparent, the intensity of which increases. In contrast to the other mucopolysaccharidoses, the organs, apart from the brain, are less affected. There are only a few abnormalities in the skeleton and the patients usually have normal physique.

Sanfilippo syndrome was named after the American pediatrician and biologist Sylvester Sanfilippo. He first described the disease in 1963.


Sanfilippo syndrome is caused by inherited defects in four different enzymes. These normally have the task of breaking down the glycosaminoglycan heparan sulfate. The enzymes SGHS (N-sulfoglucosamine sulfohydrolase), NAGLU (N-alpha-acetylglucosaminidase), HGSNAT (heparan-alpha-glucosaminide N-acetyltransferase) and GNS (N-acetylglucosamine-6-sulfatase) are affected.

The heparan sulfate is not broken down by the gene defect, so it is stored in the lysosomes. These are the functional subunits of the cells that are surrounded by their own membrane. Since the nerve cells become increasingly overloaded, this leads to disruptions in the functionality of the lysosomes, which in turn leads to complaints. The bones and other organs are not as severely affected by the disorders as in other mucopolysaccharidoses because the heparan sulfate storage is lower in them.

Symptoms, Ailments & Signs

All four forms of Sanfilippo syndrome show a uniform picture of disabilities. Significant physical and mental changes such as dementia or behavioral disorders occur in those affected. Other disorders such as hepatomegaly (enlarged liver) can also occur.

Externally, the Sanfilippo syndrome is noticeable by an enlarged tongue, full lips, a flat bridge of the nose and the emergence of coarse facial features. The hair on the head is very shaggy. Also, the eyebrows that blend into each other are dense and bushy. The affected children are becoming more and more behavioral and aggressive. They often tend towards destructive behavior.

As they lose their understanding of language, they stop speaking. Instead, they prefer gestures and facial expressions. Other possible signs include a higher susceptibility to infections , limitations in joint mobility , inguinal and umbilical hernias and sleep problems . In some cases there is also optic nerve atrophy .

As the Sanfilippo syndrome progresses, signs of paralysis appear. The sick children move more and more unsteadily and finally lose their ability to walk completely. In addition, dysphagia and epileptic seizures are a possibility.

Diagnosis & disease progression

If there is a suspicion of Sanfilippo syndrome, the attending physician determines the glycosaminoglycans in the urine. However, it is possible that the amount increases only slightly in mucopolysaccharidosis type III. For this reason, electrophoresis is performed to obtain a reliable diagnosis.

By using them, the increased excretion of heparan sulfate can be clearly recognized. In addition, the diagnosis can be made by determining the enzyme processes within the leukocytes (white blood cells) or in the fibroblasts. The course of Sanfilippo syndrome varies from person to person.

Depending on the severity of the disease, the patient dies in the second or third decade of life. In most cases, there is a significant loss of motor and mental abilities beforehand. A meaningful contact with the handicapped children is hardly possible. The death of the person concerned is usually caused by pneumonia .


As a rule, those affected by Sanfilippo syndrome suffer from a number of different disabilities. These have a very negative effect on the quality of life of the patient, so that in many cases they are dependent on the help of other people in their lives. Dementia or various behavioral disorders can also occur and thus significantly restrict the development of the person affected.

Sometimes the Sanfilippo syndrome leads to enlargement of the liver and possibly to pain. Due to the coarse facial features, the syndrome also often leads to bullying or teasing, so that the patients can also develop depression or other mental disorders. A higher susceptibility to infections or sleeping problems also occur frequently and lead to severe restrictions in everyday life.

Many of those affected also suffer from swallowing difficulties and thus from problems when taking food and liquids. Due to epileptic seizures, the life expectancy of the affected person may be significantly reduced. Unfortunately, treatment can only be symptomatic and depends on the symptoms. There are no particular complications. Furthermore, the relatives or parents are often affected by the psychological complaints.

When should you go to the doctor?

Sanfilippo syndrome must always be treated by a doctor. It may not heal on its own, and in most cases symptoms will continue to worsen if treatment of the syndrome is not initiated. A doctor should be consulted if the person concerned suffers from severe mental changes. This often leads to psychosis, depression or other mental disorders. In most cases, these symptoms appear relatively suddenly and without any particular reason and significantly reduce the quality of life of the person affected. It can also lead to changes in facial features.

If these symptoms occur, a doctor must be consulted in any case. Furthermore, sleeping problems or a very high susceptibility to infections can indicate Sanfilippo syndrome and should also be examined by a doctor. In some cases, sudden swallowing difficulties also indicate this disease. In the case of Sanfilippo syndrome, a general practitioner can be consulted in the first place . Further treatment is usually carried out by a specialist. Since the Sanfilippo syndrome is still relatively unexplored, no general prognosis can be given about the further course.

Treatment & Therapy

It is not possible to treat the causes of Sanfilippo syndrome because it is a hereditary disease. Studies on enzyme replacement therapy for mucopolysaccharidosis IIIa have been taking place since 2014. A special gene therapy is being tested to treat mucopolysaccharidosis II. In certain forms of mucopolysaccharidosis, a bone marrow transplant is considered helpful, which can alleviate the disease if it occurs before the skeletal changes begin.

In contrast to other mucopolysaccharidoses, there is still no approved enzyme replacement therapy for Sanfilippo syndrome. In order to treat the disease symptomatically, drugs are administered against the sleep disorders and hyperactivity . However, the effects of the drugs vary from child to child. There is a risk that the preparations used will lose their positive effect again after a certain period of time. It is therefore often necessary to find out an individually suitable form of therapy for the patient.

When affected children exhibit strong, aggressive, or hyperactive behavior, protective measures must often be taken in their home environment to prevent injury. In the case of swallowing disorders, switching to a mushy diet is recommended. In some cases, the use of a gastric tube is also necessary.


Sanfilippo syndrome is one of the hereditary diseases. For this reason, there are no effective preventive measures against the disease.


Sanfilippo syndrome is an inherited disorder that only allows limited follow-up care and prevention. Effective protection for patients is not available. Due to the congenital disease of the children, aftercare is primarily the responsibility of the parents. Depending on the behavior of the sick child, these can alleviate the symptoms through de-escalating measures or psychotherapy.

Doctors advise avoiding everyday stress and hectic situations to ease problems with the syndrome. Aftercare is also about reducing stress factors. Conflicts should be resolved as quickly as possible so that the child is not exposed to too much stress. Inducing periods of rest for recovery helps regulate stress levels.

For this purpose, the affected families should also talk to other people in their immediate vicinity. An explanation protects against misunderstandings and further problems. At the same time, the youngsters must not suffer from being overwhelmed. That is why parents should definitely not make direct comparisons with other children, as this would put them under pressure. The motor disorders associated with the disease can be reduced by appropriate psychotherapy.

You can do that yourself

The disease is a congenital disorder. The measures of self-help are therefore to be carried out in particular by relatives and parents. It is your responsibility to develop strategies in good time so that if the child shows aggressive behavior, de-escalation can take place as quickly as possible.

Stress and hectic everyday life should therefore be avoided. A regular daily routine can help to reduce possible stressors. Conflicts should be managed constructively and clarification of different opinions or views should be sought as quickly as possible. The child needs sufficient periods of rest so that regeneration can take place and the impressions it has received can be processed as quickly as possible. To prevent adversity, people from the social environment should be informed and enlightened about the disease and its symptoms.

Due to delays in intellectual development, it is important to ensure that the offspring is not overwhelmed during the development phase. Comparisons with playmates and schoolmates of the same age are to be avoided. Pressure and restlessness when learning new skills should also be avoided. Since there are disorders of the musculoskeletal system, physiotherapeutic measures help to alleviate symptoms. These can be carried out independently. The child’s sleep hygiene should also be checked at regular intervals and optimized according to the natural needs.

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Hello! I am Lisa Newlon, and I am a medical writer and researcher with over 10 years of experience in the healthcare industry. I have a Master’s degree in Medicine, and my deep understanding of medical terminology, practices, and procedures has made me a trusted source of information in the medical world.