Sanfilippo syndrome is the name given to a congenital metabolic disorder that occurs very rarely. It is one of the mucopolysaccharidoses.
What is Sanfilippo syndrome?
Sanfilippo syndrome is a disorder 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 which gene defect is present in Sanfilippo syndrome, physicians distinguish between the four subtypes A to D. Sanfilippo syndrome occurs only very rarely. Its frequency is 1:60,000. At birth, the affected child does not yet show any noticeable symptoms. Mucopolysaccharidosis becomes noticeable at the age of three to four years through very restless and aggressive behavior as well as the delay of mental development. From the second decade of life, in addition to the patient’s behavioral disorders, spastic paralysis appears, the intensity of which increases. However, unlike the other mucopolysaccharidoses, the organs are less affected, except for the brain. Thus, only a few abnormalities are seen in the skeleton and patients usually have normal body growth. Sanfilippo syndrome is named after the American pediatrician and biologist Sylvester Sanfilippo. The latter first described the disorder in 1963.
Causes
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 affected are SGHS (N-sulfoglucosamine sulfohydrolase), NAGLU (N-alpha-acetylglucosaminidase), HGSNAT (heparan-alpha-glucosaminide N-acetyltransferase), and GNS (N-acetylglucosamine-6-sulfatase). The heparan sulfate is not degraded by the gene defect, so it is stored in the lysosomes. These are the functional subunits of the cells, which are surrounded by their own membrane. As the nerve cells become increasingly overloaded, this leads to disturbances in the functioning of the lysosomes, which in turn causes complaints. The bones as well as the other organs are not affected by the disorders as much as in other mucopolysaccharidoses because heparan sulfate storage is lower in them.
Symptoms, complaints, and signs
All four forms of Sanfilippo syndrome present a consistent picture of disability. Thus, affected individuals experience significant changes in their physique as well as their psyche, such as dementia or behavioral disorders. In addition, other disorders such as hepatomegaly (enlargement of the liver) may occur. Externally, Sanfilippo syndrome is noticeable by an enlargement of the tongue, full lips, a flat nasal bridge, and the prominence of coarse facial features. The main hair turns out very shaggy. In addition, the eyebrows, which merge into each other, are dense and bushy. The affected children become more and more behavioral and aggressive. Not infrequently, they tend to behave destructively. As they lose their understanding of speech, they stop speaking. Instead, they prefer gestures and facial expressions. Other possible signs include greater susceptibility to infections, joint mobility limitations, inguinal and umbilical hernias, and sleep problems. In some cases, optic nerve atrophy is also present. In the further course of Sanfilippo syndrome, paralysis symptoms appear. In this process, the affected children move more and more unsteadily and eventually lose their ability to walk completely. In addition, swallowing disorders and epileptic seizures are within the realm of possibility.
Diagnosis and course of the disease
If Sanfilippo syndrome is suspected, the treating physician determines the glycosaminoglycans in the urine. However, it is possible that their amount increases only slightly even in mucopolysaccharidosis type III. For this reason, electrophoresis is performed to obtain a reliable diagnosis. By using it, the increased excretion of heparan sulfate can be clearly identified. In addition, the diagnosis can be made by determining the enzyme sequences within the leukocytes (white blood cells) or in the fibroblasts. The course of Sanfilippo syndrome varies from individual to individual. Depending on the severity of the disease, death occurs in the second or third decade of life.In most cases, a significant loss of motor and mental abilities occurs beforehand. A meaningful contact with the disabled children is hardly possible. The death of the affected person is usually caused by pneumonia.
Complications
As a rule, those affected with Sanfilippo syndrome suffer from a number of different disabilities. These have a very negative effect on the patient’s quality of life, so that in many cases they are dependent on the help of other people in their lives. Dementia or various behavioral disorders may also occur, thus significantly limiting the development of the affected person. Sometimes Sanfilippo syndrome leads to an enlargement of the liver and thus possibly to pain. Due to the coarse facial features, the syndrome also often leads to bullying or teasing, so that patients may also suffer from depression or other psychological upsets. A higher susceptibility to infections or sleep problems also frequently occur and lead to severe restrictions in everyday life. Likewise, many affected persons suffer from swallowing difficulties and thus from discomfort when taking food and liquids. Due to epileptic seizures, the life expectancy of the affected person may be considerably reduced. Unfortunately, treatment can only be symptomatic and depends on the symptoms. Special complications do not occur. Furthermore, the relatives or parents are often also affected by the mental complaints.
When should one go to the doctor?
Sanfilippo syndrome must always be treated by a doctor. There can be no self-healing, with symptoms continuing to worsen in most cases if treatment for the syndrome is not initiated. A doctor should be consulted if the affected person suffers from severe psychological changes. Psychoses, depressions or other disorders of the psyche often occur. In most cases, these complaints occur relatively suddenly and without any particular reason, and significantly reduce the quality of life of the affected person. This can also lead to a change in facial features. If these complaints occur, a doctor must be consulted in any case. Furthermore, sleep complaints or a very high susceptibility to infections can also indicate Sanfilippo syndrome and should also be examined by a medical professional. In some cases, sudden dysphagia may also be a sign of the disease. In the case of Sanfilippo syndrome, a general practitioner can be consulted in the first instance. Further treatment is usually by a specialist. Because Sanfilippo syndrome is still relatively unexplored, no general prognosis can be given about its further course.
Treatment and therapy
Treatment of the causes is not possible in Sanfilippo syndrome because it is a hereditary disease. Studies of enzyme replacement therapy for mucopolysaccharidosis IIIa have been taking place since 2014. A specific gene therapy is being tested to treat mucopolysaccharidosis II. In certain forms of mucopolysaccharidosis, bone marrow transplantation is thought to be helpful in alleviating the disease, provided it occurs before the onset of skeletal changes. Unlike other mucopolysaccharidoses, there is not yet an approved enzyme replacement therapy for Sanfilippo syndrome. To treat the condition symptomatically, medications are administered for the sleep disturbances as well as the hyperactivity. However, the effects of the drugs vary from child to child. There is a risk that the drugs used will lose their positive effect after a certain time. It is therefore often necessary to find an individually suitable form of therapy for the patient. If the affected children suffer from strong, aggressive or hyperactive behavior, protective measures often have to be taken in their home environment to prevent injuries. In cases of dysphagia, switching to a pulpy diet is recommended. In some cases, the use of a feeding tube may also be required.
Prevention
Sanfilippo syndrome is considered a hereditary disorder. For this reason, there are no effective preventive measures against the disease.
Follow-up
Sanfilippo syndrome is a hereditary disorder that allows only limited follow-up and prevention. Effective protection for patients is not available.Due to the congenital disease of the children, the aftercare is mainly 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 the problems with the syndrome. Thus, follow-up care is about reducing stress factors, among other things. Conflicts should be resolved quickly, if possible, so that the child is not exposed to too much stress. Inducing periods of rest for regeneration helps regulate stress levels. To this end, affected families should also talk to others in their immediate environment. Clarification protects against misunderstandings and further problems. At the same time, the offspring must not suffer from excessive demands. For this reason, parents should under no circumstances make direct comparisons with other children, as this would put pressure on them. The motor function disorders associated with the disease can be reduced by appropriate psychotherapy.
This is what you can do yourself
The disease is a congenital disorder. Therefore, the measures of self-help are to be carried out especially by relatives and parents. It is incumbent on them to develop strategies in good time so that de-escalation can take place as quickly as possible if aggressive behavior occurs in the child. Stress and hectic in everyday life should therefore be avoided. A regulated daily routine can help to reduce possible stressors. Conflicts should be handled constructively and clarification of different opinions or views should be sought as quickly as possible. The child needs sufficient rest periods so that regeneration can take place and absorbed impressions can be processed as quickly as possible. To prevent adversity, people in the social environment should be informed and educated about the disease and its symptoms. Due to delays in mental development, care should be taken not to overtax the offspring during the developmental phase. Comparisons with playmates and schoolmates of the same age should be avoided. Likewise, pressure and restlessness should be avoided when learning new skills. As disorders of the musculoskeletal system occur, physiotherapeutic measures help to alleviate complaints. These can be carried out independently. At regular intervals, the child’s sleep hygiene should also be checked and optimized according to natural needs.
