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 What is Sanfilippo? Sanfilippo Syndrome is a disorder than originates from a genetic error of metabolism. It is caused by the deficit of an enzyme that is needed to transform a specific substance in the body called Heparan Sulfate (HS). Due to the enzyme missing, HS accumulates in the body and specifically in the Central Nervous System. This is a "storage" or lysosomal disorder. Over time, children experience deep and severe deterioration and a loss of function in several crucial areas of the body. They progressively suffer from increasing mental and physical disability. Their life expectancy is dramatically shortened. What is a lysosomal disorder? What is Sanfilippo Syndrome? Inheritance Pattern: Autosomal Recessive Clinical signs Diagnosis The way to therapies What is a lysosomal disorder? The lysosomal disorders are a group of rare genetic disorders caused by the deficiency of one of the lysosomal enzymes. Lysosomal enzymes are to be found in the lysosome. The lysosome is a very small membrane-contained body located in the cytoplasm of numerous cells. The Mucopolysaccharidoses, also known as MPS Disorders, are a group of lysosomal disorders. In the MPS disorders, the deficient or missing enzyme will not be able to properly transform complex carbohydrates called mucopolysaccharides into simpler molecules. The accumulation of mucopolysaccharides in the cells causes the severe neurological and/or physical symptoms and developmental deficits that characterize these disorders. MPS-III (Mucopolysaccharidose type III) is one of seven MPS Disorders. What is Sanfilippo Syndrome? MPS III is also known as Sanfilippo Syndrome. MPS III is a lysosomal storage disease belonging to the group of Mucopolysaccharidoses, in which the affected individuals lack one lysosomal enzyme responsible for the degradation of Heparan Sulfate (HS). HS is a very important constituent of the tissues throughout the body and in affected patients partially degraded HS progressively accumulates within the lysosome, ultimately causing cell, tissue and organ dysfunction by a partly unknown pathophysiological mechanism. MPS III mainly affects the central nervous system. The disorder is recessive, and seems to affect males and females equally. MPS III is a rare disorder with prevalence difficult to assess, due to the fact that the disease is under diagnosed. The published prevalence varies between 1:24,000 (Netherlands) and 1:120,000 (Australia) live births for the type A. It is much lower for types C and D (below 1:1,000,000). Historically, MPS III has been considered to mainly take severe forms even if milder forms have been reported. The underlying factors for mild or severe forms remain widely unexplained. MPS III subtypes A, B, C, D, refer to deficiency in four different enzymes, each responsible for the degradation of heparan sulfate: heparan sulfamidase for MPS IIIA, alpha-N-acetylglucosaminidase for MPS IIIB, alpha-glucosaminide N-acetyltransferase for MPS IIIC, and N-acetylglucosamine-6-sulfate sulfatase for MPS IIID. Inheritance Pattern: Autosomal Recessive As most of MPS disorders, Sanfilippo Syndrome has an autosomal recessive mode of inheritance. This means that the disorder occurs only if both parents carry the abnormal gene. When both parents have such an abnormal gene, there is a one-in-four chance of every child having Sanfilippo Syndrome or 25% in each pregnancy. The unaffected children have in their turn a 2 in 3 chance of being carriers like their parents, and a 1 in 3 chance of being a normal non-carrier. Clinical signs A Sanfilippo baby will probably appear unaffected at birth. The baby will also probably show a very normal development for about the first two years. The first signs can vary from one child to another. The first recognisable symptoms though usually appear between the ages of 2 and 6 years, with mental deterioration and behavioural disorders such as hyperkinesia, aggressiveness. Ear infections, runny noses and chronic colds will also draw the medical attention. Mental retardation progressively affects the children as they grow. Even though Sanfilippo Syndrome is mainly known to severely deteriorate the Central Nervous System, it also has skeletal involvement. In most children MPSIII involves joint changes with limitation of movement. As in other MPS disorders, multiple organs are involved. The children may suffer from mild forms of dysmorphism, thickened skin, excessive hair growth, chronic runny nose, chronic ear infections causing hearing loss, and a projected life expectancy of ten to twenty years. Diagnosis Diagnosis is usually made upon finding increased levels of HS in urine. Cases where Sanfilippo Syndrome has been diagnosed before the age of 2 due to the awareness of paediatricians are also reported. Specific symptoms such as an enlargement of the liver and spleen, chronic runny noses, ear infections, have helped diagnose this disease sooner. Nevertheless, at this stage, MPSIII is mainly diagnosed after the age of 2. (FAIRE UN POINT SUR LE SUJET The Sanfilippo Alliance is active in helping to improve the quality of diagnosis and evaluation tools.) The way to therapies To date, there is no treatment available to cure MPS III. However, there is research being done worldwide on MPS, including on Sanfilippo Syndrome. The key countries taking part in research for MPS diseases are the United States, Australia, Canada, different countries throughout Europe, and Israel. As research and technology improve, we are confident that there is a future for our children. The Sanfilippo Alliance is active in helping to directly fund research into MPSIII and related diseases: Project S.O.A.R. (State Of the Art Report) |
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Alliance Sanfilippo - BP 88 - 92203 - Neuilly sur Seine Cedex France - Tel. + 33 6 14 03 84 87 |
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