Sanfilippo syndrome: symptoms, causes and treatment.

An overview of the characteristics of Sanfilippo syndrome, a rare metabolic disease.

Sanfilippo syndrome is a very rare condition with genetic causes. and is caused by a problem in one of the four genes responsible for generating the enzymes that degrade 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 therefore the enzyme that is altered.

This syndrome has serious effects on cognitive, affective and behavioral development, altering the subject's behavior and physiological functionality. Such is the severity that patients with this problem usually do not live beyond adolescence, since this syndrome has no cure and can only be treated palliatively. Currently, research and testing of new therapies that are more effective and can prolong the lives of these patients continues.

In this article, we will see what is the rare Sanfilippo SyndromeIn this article, we will see what is the rare Sanfilippo syndrome, what are its causes, the symptoms presented by the subjects who suffer it, what is the prevalence of its appearance, what techniques are used to diagnose it, what is its prognosis and what treatments are currently performed and which ones are in the experimental phase.

What is Sanfilippo syndrome?

Sanfilippo syndrome, also known as mucopolysaccharidosis type III, is a metabolic disease of very low occurrence of genetic origin. This affectation is part of the lysosomal storage diseases, where there is an alteration in the process of decomposition of sugar molecules, carbohydrates, which causes serious affectations in the individual that will cause the premature death of the subject.

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

Causes

This syndrome has genetic causes, specifically autosomal recessive transmission.. is caused by an alteration in one of the four genes that is responsible for producing the enzyme that degrades heparan sulfate, this name is given to a type of sugar molecules called glycosaminoglycans (GAG) or also called mucopolysaccharides, which is why this syndrome may also receive this name.

Why are these sugar molecules formed? These molecules, which are present in the form of long chains, perform various important functions for the organism: they are necessary for the Blood to clot properly (i.e. a fundamental function when we sustain a wound), they have a structural function, they are part of the skin and of connective, cartilaginous and nervous tissue and are useful in the transmission of information between cells.

The affectation occurs in one of the four genes responsible for producing the enzyme that decomposes this sugar molecule.As there are 4 different genes, there will also be 4 different types of Sanfilippo syndromes, although in all of them an abnormal accumulation of heparan sulfate in the cell will be observed, which will produce serious and multiple affections such as: growth and behavioral problems, alterations in mental development and affectation in different organs.

The enzymes are named according to the type of gene that generates them: gene type A produces heparan sulfamidase; gene type B is necessary for the creation of the enzyme alpha-N-acetylglucosaminidase; gene type C 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 is rare, occurring overall in 1 in 70,000 births.although it has been seen that the proportion varies according to the country where the study is carried out.

In this line, an investigation carried out in Australia showed that the most prevalent type of syndrome is type A with an approximate incidence of 1 in every 100,000 births, representing 60% of the cases of this affectation; type B shows an incidence close to 1 birth in every 200,000, representing 30% of the cases; and with much smaller percentages are type D, which affects 1 in every 1,000,000 cases. 000, representing 30% of the cases; and with much smaller percentages are type D, which affects 1 in every 1,000,000 births, representing 6% of the cases, and type C, which represents 1 birth in every 1,500,000, representing 4% of the cases.

We also know that this is an autosomal recessive disorder. The affected genes are not the sexual pairs and therefore the incidence in males and females will be the same.. The term "recessive" means that of the two genes that provide information, both from the mother and the father, to generate the enzymes, it is necessary that both are altered and present the affectation, since if only one of them is present, the individual will be a carrier of the disease but will not develop it.

The prognosis of this alteration is not good, it causes intellectual disability that can become severe and can be below an IQ of 50.. The average years of life are usually in adolescence, in some cases it can last a little longer and in others where the impact is more severe, as in the case of type A, the patient has a more premature death.

Characteristic symptoms of Sanfilippo syndrome.

Sanfilippo syndrome, being of genetic origin, will be present from the birth of the child, although it is not until the period of 2 to 5 years when the problem and affectation begins to develop and become visible..

The consequences are devastating, producing a global delay in the child's development, which can even affect and end up losing abilities that he/she already had. Thus, we observe multiple alterations in behavior, in the development of cognitive abilities or in biological functions..

Language impairment, progressive loss of motor skills, severe hearing and visual impairment, sleep problems, severe cognitive impairments that cause deterioration in adaptive and social skills and behavioral problems (tendency to be more aggressive and hyperactive, with attention deficit, with sudden changes in mood and self-injurious behaviors).

In reference to physiological signs heart and lung problems, loss of sphincter control, stiffer than normal joints, frequent diarrhea, headache and enlarged head size have been observed.The syndrome is degenerative, i.e., the patient loses the ability to control the sphincter, joints are stiffer than normal, frequent diarrhea, headache and head size is larger than normal.

We see then that the syndrome is degenerative, that is to say, that symptoms will appear progressively affecting more and more the functionality and the life of the patient, leading to a death. the patient, leading to a premature death.

Given the rarity of this condition, it will not be one of the first diagnoses to be considered when the first symptoms appear. In order to confirm that Sanfilippo syndrome is present, the first test to be performed is a urine analysis to detect whether high concentrations of hefilippo sulfate are present in the urine. high concentrations of heparan sulfate, which fails to degrade.which fails to degrade. Once it is confirmed that the concentration is high, we proceed with a more specific study of the type of enzyme that is missing, since as we have seen we have 4 types related to the different enzymes.

Also can also be diagnosed by means of imaging tests such as an X-ray, in which, if the enzyme is present, it is possible to diagnose it byin which, if the syndrome is present, a mild dysostosi multiplex is observed, i.e., bone involvement, or by means of a brain tomography which uses X-rays to observe brain function (in this case we will see that in the early stages of the alteration a mild or moderate cortical atrophy appears and in the more advanced stages this atrophy is already more severe).

It is important to know the type of syndrome that each subject presents, since according to the missing enzyme the affectation will be more or less severe, being the most severe the type A.

Treatment

Sanfilippo syndrome has no cure, and for this reason its treatment is palliative, which means that we can reduce and improve symptoms but we cannot make the disease disappear.This means that we can diminish and improve the symptoms but we cannot make the disease disappear.

Thus, we try to work and train the different cognitive and motor skills of the subject so that the degeneration is as slow as possible and can have the maximum quality of life for as many years as possible.

Given the seriousness of the syndrome, research continues to find a more effective treatment that obtains better results. Thus, we are currently enzyme treatment and gene therapy with types A and B are currently being studied.. Similarly, it is also being tested whether the ketogenic diet, which consists of eating fewer carbohydrates, can delay the onset of symptoms.