Sanfilippo Syndrome: Symptoms, Causes And Treatment
Sanfilippo syndrome is a very rare condition that has genetic causes and it 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. In this way, we will talk about type A, B, C or D depending on the type of gene affected and therefore the enzyme that is altered.
This syndrome produces serious effects on both cognitive and affective development as well as behavioral development, altering the subject’s behavior and 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. Currently, new therapies that are more effective and can prolong the life of these patients continue to be researched and tested.
In this article, we will see what rare Sanfilippo syndrome is what are its causes, the symptoms presented by subjects who suffer from it, what prevalence of appearance does it have, what techniques are used to diagnose, what is its prognosis and what treatments are currently being carried out and which are in the experimental phase.
Sanfilippo syndrome, also called mucopolysaccharidosis type III, is a very low onset metabolic disease and of genetic origin. This condition is part of the lysosomal storage diseases, where there is an alteration in the decomposition process of sugar molecules and carbohydrates, a fact that causes serious effects on the individual that will cause the premature death of the subject.
This syndrome, as we said in the previous paragraph, gives rise to an alteration in the lysosomes; these are a type of organelles that make up the cell and contain digestive enzymes, being therefore important for cellular digestion and recycling of the waste that is produced. It has been observed that alterations in this organelle lead to fatal consequences.
Causes
This syndrome It has genetic causes, specifically autosomal recessive transmission It 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 glucosaminoglycans (GAG) or also called mucopolysaccharides, which is why which 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 blood to clot properly (that is, a fundamental function when we get a wound), they have a structural function, they 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 involvement in different organs.
The name given to the 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.
Prevalence of this syndrome
Sanfilippo syndrome It is rare, generally occurring in 1 in every 70,000 births although it has been seen that the proportion varies depending on the country where the study is carried out.
Along these lines, research 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, accounting for 60% of the cases of this condition; type B shows an incidence close to 1 birth in every 200,000, representing 30% of cases; and with much smaller percentages are type D, which affects 1 in every 1,000,000 births, accounting for 6% of the cases, and type C, which affects 1 birth in every 1,500,000, accounting for 4% of the cases. .
Likewise, we know that this is an autosomal recessive condition. The affected genes 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, from both 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 carry the disease but will not develop it.
The prognosis of this alteration is not good, entails intellectual disability that can be serious, falling below an IQ of 50 The average years of life are usually in the teens, on some occasions it can last a little longer and on others where the impact is more serious, as in the case of type A, the patient dies more prematurely.
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, resulting in a global delay in the child’s development, 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
Language impairment appears, progressive loss of motor ability, severe auditory and visual impairment, sleeping 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 with self-harming behaviors).
In reference to physiological signs heart and lung problems have been observed loss of the ability to control the sphincter, stiffer joints than normal, frequent diarrhea, headache and larger size of the headache.
We see then that the syndrome is degenerative, that is, that The symptoms will appear progressively, affecting functionality and life more and more of the patient, leading to premature death.
Given the rarity of this condition, it will not be one of the first diagnoses that will be considered when the first symptoms appear. In order to confirm that you have Sanfilippo syndrome, the first test that will be performed will be a urine analysis to detect if they appear. high concentrations of heparan sulfate, which fails to degrade. Once confirmed that the concentration is high, we continue 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 It can be diagnosed through imaging tests such as an x-ray in which, if the syndrome is present, mild multiple dysostosis is observed, that is, bone involvement, or through a brain tomography that uses X-rays to observe brain functioning (in this case we will see that in the first phases of The alteration appears as a mild or moderate cortical atrophy and in the more advanced phases this atrophy is already more serious).
It is important to know the type of syndrome that each subject presents, since depending on the enzyme that is missing, the affectation will be more or less serious, with type A being the most severe.
Treatment
Sanfilippo syndrome has no cure, and for this reason its treatment is palliative which means that we can reduce and improve the symptoms but we cannot 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 the subject can have the highest quality of life for the greatest number of years.
Given the severity of the syndrome, research continues to find a more effective treatment that obtains greater results. In this way, currently It is being studied how enzyme treatment and gene therapy works with types A and B Similarly, it is also being tested whether the ketogenic diet, which consists of eating fewer carbohydrates, can delay the appearance of symptoms.
