Sanfilippo syndrome: symptoms, causes and treatment

Sanfilippo syndrome is a very rare condition that has genetic causes. and it occurs due to a problem in one of the four genes responsible for generating the enzymes that degrade heparan sulfate, a type of sugar molecule. In this way, we will speak of type A, B, C or D according to the type of gene affected and therefore the enzyme that is altered.

This syndrome produces serious affectations both in the development cognitive and affective and behavioral, altering the behavior of the subject and its physiological functionality. Such is the severity that patients with this problem do not usually live beyond adolescence, since this syndrome has no cure and can only be treated palliatively. New therapies that are more effective and can prolong the life of these patients are currently being investigated and tested.

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

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What is Sanfilippo syndrome?

Sanfilippo syndrome, also called type III mucopolysaccharidosis, is a very low-onset metabolic disease and of genetic origin. This affectation is part of lysosomal storage diseases, where there is an alteration in the decomposition process of sugar molecule, carbohydrates, a fact that 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, gives rise to an alteration in the lysosomes; these are a kind of organelles that make up the cell and contain digestive enzymes, therefore being important for cellular digestion and recycling of the waste that is produced. Alterations in this organelle have been observed to lead to fatal consequences.

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Causes

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

Why are these types of sugar molecules formed? These molecules, which are presented in the form of long chains, perform different important functions for the body: they are necessary for the blood to clot properly (that is, a fundamental function when we injure ourselves), they have a function structural, are part of the skin and connective, cartilaginous and nervous tissue and are useful in the transmission of information between cells.

The affectation occurs in one of the four genes that are 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 all of them an abnormal accumulation of heparan sulfate will be observed in the cell, which will produce serious and multiple conditions such as: growth and behavior problems, alterations in mental development and affectation in different organs.

The name given to enzymes according to the type of gene that 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.

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Prevalence of this syndrome

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

Along these lines, 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, assuming this 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 births assuming 6% of the cases, and type C, which represents 1 birth in every 1,500,000 being 4% of the cases.

Likewise, we know that this is an autosomal recessive condition. The genes affected are not the sexual pairs and therefore the incidence in men and women 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 not it will develop.

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

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Characteristic symptoms of Sanfilippo syndrome

Sanfilippo syndrome, being of genetic origin, It 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 development of the child, which can even affect and end up losing abilities that they already had. Thus we observe multiple alterations in behavior, in the development of cognitive abilities or in biological functions.

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

In reference to physiological signs heart and lung problems have been observed, loss of ability to control the sphincter, stiffer than normal joints, frequent diarrhea, headache and larger headache.

We therefore see that the syndrome is degenerative, that is, that the symptoms will appear progressively, affecting more and more functionality and life of the patient, leading to 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 you have Sanfilippo syndrome, the first test that will be carried out will be the analysis of the urine to detect if they appear high concentrations of heparan sulfate, which fails to degrade. Once it has been confirmed that the concentration is high, 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.

Too can be diagnosed by imaging tests such as an x-ray, in which, if the syndrome is present, a mild multiple dysostosis is observed, that is, a bone involvement, or by means of a tomography brain that uses X-rays to observe brain function (in this case we will see that in the early stages of the alteration a atrophy cortical mild or moderate 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 depending on the enzyme that the lack of it, the affectation will be more or less serious, the most severe being type A.

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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 can not make the disease disappear.

Thus, an attempt is made to work and train the subject's different cognitive and motor skills so that degeneration is as slow as possible and you can have the highest quality of life for the greatest number of years.

Given the severity of the syndrome, research is continuing to find a more effective treatment with greater results. Thus, currently how enzyme treatment and gene therapy work with types A and B is being studied. Similarly, it is also being tested whether the ketogenic diet, which consists of eating less carbohydrates, can delay the appearance of symptoms.