Sanfilippo Syndrome

Sanfilippo syndrome it is a metabolic disorder, genetic character, autosomal recessive, characterized by the absence of mucopolysaccharides III, which are responsible for the breakdown of long chains of glycosaminoglycans (GAGs).

It is part of a group of diseases called mucopolysaccharidoses (MPS). Specifically, it is called MPS III (III-A, III-B, III-C and III-D). Is called Sanfilippo syndrome named after the doctor who first reported some cases of the disease in 1963, Dr. Sylvester Sanfilippo.

This disease occurs when there is a defect or lack the necessary enzymes in the breakdown and recycling of the GAGs found in the body, heparan sulphate. When there is a complete breakdown of the GAG, there is an accumulation of the same inside the cells of the body, causing progressive damage. Typically, the clinical manifestations arise between 2 to 6 years old.

There are four distinct types of this syndrome:

• Type A (MPS IIIA): the most severe form. In this case, with this syndrome have an altered form or do not exhibit the so-called heparan N-sulfatase.

• Type B (MPS IIIB) occurs when the deficient enzyme is named alpha-N-acetylglucosaminidase.

• Type C (MPS IIIC): in this case the deficient enzyme is called acetyl-CoA acetyl-alpha-glucosamine.

• Type D (MPS III-D): the enzyme that is deficient is N-acetylglucosamine 6-sulfatase.

Thus, each individual MPS III shows a specific type of same: A, B, C or D, and the type determination must be made by means of biochemical tests.

Surveys conducted in the Netherlands show that the incidence of this disease is around 1 out of every 70,000 live births and the type A most common in northwestern Europe, type B, in southeastern Europe, and types C and D rare at all places. In Brazil, there is apparently one of MPS III under diagnosis in relation to other MPS, once the first is primarily neurological involvement, while the remainder is primarily physical.

Since all the four types of MPS III accumulate the same GAG ​​the heparan sulfate almost no clinical difference between them. Similarly to other MPS, there is also the presence of physical changes, but milder. This syndrome causes facial features slightly altered, delayed development metal that evolves to severe mental retardation, abnormal gait and speech, stiffness and joint behavioral changes.

Other clinical manifestations that can be observed in Sanfilippo syndrome are frequent airway infections, chronic runny nose, bad teeth, sleep apnea, macroglossia, cold hands and feet, hepatosplenomegaly, lymphadenopathy, altered bowel habits, seizures, hydrocephalus and hearing loss .

Diagnosis and Treatment

The diagnosis can be made through the framework and clinical history presented by the child, as confirmed by tests of enzyme levels in tissue samples and genetic sequencing. There is also the possibility of prenatal diagnosis, when you already have a child with MPS III. This requires knowing what type of MPS III of affected child, because for each type of MPS III, there is a distinct diagnostic test, and all the brethren who hold the MPS III present the same type of disease.

The treatment, in large part, is supported, as behavioral disturbances caused by the syndrome does not respond well to drugs. When diagnosed early, the bone marrow transplant can provide positive results. Although it is possible to synthesize the enzyme deficient in lab and administer it intravenously, it can not cross the blood-brain barrier and thus there is no way to treat the neurological manifestations of the syndrome. However, many studies are being developed in the search for an effective solution for Sanfilippo syndrome.