Sanfilippo Syndrome: Symptoms, Causes and Treatment

Sanfilippo syndrome is a very rare disease that has genetic causes and is caused by a problem in one of the four genes responsible for generating the enzymes that break down heparan sulfate, a type of sugar molecule. Thus, we will speak of type A, B, C or D depending on the type of gene affected and, consequently, the enzyme which is altered.

This syndrome causes severe impairment of cognitive, affective and behavioral development, modifying the behavior and physiological functionality of the subject. It is the severity that patients with this problem usually do not experience beyond their teenage years, as this syndrome is not treated and can only be treated palliatively. New therapies that are more effective and likely to prolong the lives of these patients are still being researched and tested.

In this article we will look at what is rare Sanfilippo syndrome, what are the causes, the symptoms of the subjects who suffer from it, what is the prevalence of its appearance, what techniques are used to diagnose it, what is its prognosis and what treatments are in progress and which are in the experimental phase.

    What is Sanfilippo Syndrome?

    Sanfilippo syndrome, also called type III mucopolysaccharidosis, is a disease with a very low metabolism and genetic origin. This condition is part of lysosomal overload diseases, where there is an alteration in the process of breaking down the sugar molecule, carbohydrates, which causes severe damage to the individual which will lead to the premature death of the subject.

    This syndrome, as we said in the previous paragraph, results in an alteration of the lysosomes; these are a kind of organelles that make up the cell and contain digestive enzymes, being therefore important for cell digestion and the recycling of waste that takes place. It has been observed that alterations of this organelle lead to fatal consequences.


      This syndrome it has genetic causes, especially autosomal recessive inheritance. is caused by an alteration in one of the four genes responsible for producing the enzyme that breaks down heparan sulfate, this name is the one that receives a type of sugar molecule called glucosaminoglycans (GAG) or even called mucopolysaccharides, reason for which this syndrome can also be called so.

      Why do these types of sugar molecules form? These molecules, which are in the form of long chains, fulfill various important functions for the organism: they are necessary for the good coagulation of the blood (that is to say a fundamental function when we make a wound), they have a function Structurally, they are part of the skin and connective, cartilage and nervous tissue and are useful in transmitting information between cells.

      Involvement occurs in one of the four genes responsible for producing the enzyme that breaks down this sugar molecule.; as there are 4 different genes there will also be 4 different types of Sanfilippo Syndromes although in each of them abnormal accumulation of heparan sulfate will be observed in the cell which will produce severe and multiple conditions such as : growth and behavior, alterations in mental development and impairment in different organs.

      The names given to enzymes according to the type of gene which generates them are: the type A gene produces heparan sulfamidase; the type B gene is necessary for the creation of the enzyme alpha-N-acetylglucosaminidase; the type C gene gives rise to the enzyme called alpha-glucosaminide N-acetyltransferase; and finally type C, which produces the enzyme N-acetylglucosamine-6-sulfate-sulfatase.

        Prevalence of this syndrome

        Sanfilippo syndrome it is rare, generally occurring in 1 in 70,000 births, although we have seen that the proportion varies according to the country where the study is carried out.

        With this in mind, research in Australia has shown that the most common type of syndrome is type A with an incidence of about 1 in 100,000; this represents 60% of cases of this condition; type B has an incidence of close to 1 birth in 200,000, representing 30% of cases; and with much lower percentages, there is type D, which affects 1 birth in 1,000,000 representing 6% of cases, and type C, which represents 1 birth in 1,500,000 or 4% of cases.

        We also know that it is an autosomal recessive disease. The affected genes are not sexual partners and therefore the incidence in men and women will be the same. The term “recessive” means that of the two genes which provide information, both from the mother and the father, to generate the enzymes, both must be modified and exhibit the affect, because if it is present only in one of them, the individual will be the carrier of the disease but will not develop it.

        The prognosis for this disorder is not good, involves an intellectual disability that can be severely below an IQ of 50. The middle years of life are usually in the teenage years, sometimes it can last a little longer and in others where the impact is more severe, such as in the case of type A, the patient dies more prematurely.

          Characteristic symptoms of Sanfilippo syndrome

          Sanfilippo syndrome, being of genetic origin, will be present from the birth of the child, although this is only from the period of 2 to 5 years when the problem and affectation begins to develop and be visible.

          The consequences are devastating resulting in an overall delay in the development of the child, which can even affect and eventually lose abilities he already possessed. So we look at the multiples alterations in behavior, development of cognitive abilities or biological functions.

          Language disorders, progressive loss of motor skills, severe hearing and visual impairment, sleep problems, severe cognitive impairment leading to impaired adaptive and social skills, and behavior problems (tendency to be more aggressive and hyperactive, attention deficit , abrupt mood swings, and self-injurious behaviors).

          As for physiological signs heart and lung problems have been observed, loss of ability to control the sphincter, stiffer than normal joints, frequent diarrhea, headache and height increase.

          We can therefore see that the syndrome is degenerative, that is to say that symptoms will appear gradually affecting more and more functionality and life of the patient, which led to his premature death.

          Considering the rarity of this condition, it will not be one of the first diagnoses to be investigated when the first symptoms appear. In order to confirm that you have Sanfilippo syndrome, the first test that will be done will be a urine test to detect if they appear. high concentrations of heparan sulfate, which does not degrade. Once it is confirmed that the concentration is high, we proceed to a more specific study of the type of enzyme that is missing, because as we have seen we have 4 types related to different enzymes.

          too much can be diagnosed by imaging tests such as an x-ray, in which, if the syndrome is present, there is mild multiple dysostosis, i.e. bone involvement, or by means of a brain tomography that uses x-rays to observe the brain operation (in this case we will see that in the first phases of the alteration a light or moderate cortical atrophy appears and in the more advanced phases this atrophy is already more severe).

          It is important to know the type of syndrome that each subject presents, because depending on the enzyme that is missing, the condition will be more or less severe, the most severe being type A.


            Sanfilippo syndrome has no cure, so its treatment is palliative, which means we can reduce and improve the symptoms, but we cannot make the disease go away.

            So, we try to work and train the different skills cognitive and motor skills of the subject so that the degeneration is as slow as possible and can have the best quality of life for as long as possible.

            Given the severity of the syndrome, more research is underway to find a more effective and efficient treatment. More results. In this way, currently studies how enzyme therapy and gene therapy work with types A and B. Likewise, it is also tested whether the ketogenic diet, which consists of ingesting less carbohydrates, can delay the onset of symptoms.

            Bibliographical references

            • Association of Mucopolysaccharides and Related Syndromes (2012) MPS III O Sanfilippo Syndrome. Practical guide to understanding the disease. Cravelona, ​​Spain.
            • Sanfilippo Stop Foundation (2016) Clinical guide to Sanfilippo syndrome.
            • National MPS Society (2006) Guide to understanding Sanfilippo syndrome. Mucopolysaccharide (MPS) III

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