Sanfilippo syndrome

The Sanfilippo syndrome is a rare congenital, hereditary metabolic disease. It is one of the mucopolysaccharidoses, a group of disorders of the degradation of long-chain sugar molecules, the glycosaminoglycans. As Sanfilippo syndrome type III is called the mucopolysaccharidoses, which in turn into four types ( AD) is divided. Affected children are normal in birth. From the third to fourth year of life, a retarded mental development and an aggressive, extreme restlessness sets (hyperactivity ). Around the second decade of life, the behavior disorder occurs in the background and is replaced by an increasing spastic paralysis. In contrast to the other mucopolysaccharidoses other organs except the brain less affected. For example, the patients are usually moderate rate and have little skeletal abnormalities. A causal therapy does not exist, so that the treatment is purely symptomatic,.

Cause

The Sanfilippo syndrome is caused by an autosomal recessive defect of four different enzymes ( type AD ) to the glycosaminoglycan heparan sulfate degrade.

The non-degraded heparan sulfate in small, enclosed by its own membrane functional subunits of the cells ( organelles ), the lysosomes, stored ( lysosomal storage disease). With increasing overload, especially of nerve cells, they are more and more disturbed in their function and leads to the corresponding symptoms. In the bones and other organs storage of heparan sulfate is not as pronounced, so that these institutions are in contrast to other mucopolysaccharidoses not as severely affected.

Symptoms

At birth, children are initially completely unobtrusive. With the beginning of the second to fourth year of life, they remain increasingly behind in their development. They also get a noticeable restless, hyperactive and often aggressive, destructive behavior. In this phase, affected patients also have distinct sleep disorders. The children cease to speak and lose the understanding of language. It was only later added increasing paralysis. The children run more and more uncertain and lose the ability to walk eventually, due to spastic paralysis altogether. You are playing in swallowing disorders, which increasingly lead to difficulties in the diet. Also epilepsy may reflect the increasing disorder of brain function. Against the sides of the symptoms of the nervous system disease symptoms in other organs in comparison to the other are low mucopolysaccharidoses pronounced. The body length reaches almost normal proportions, facial features are coarsened only with a pronounced deterioration of brain function somewhat. Only the hair is remarkably thick and brittle. The eyebrows are so bushy that they sometimes grow together in the middle. The course is highly variable, depending on the severity of the patients die in the second or third decade of life.

Diagnosis

If you suspect the presence of a Sanfilippo syndrome may first be carried in the urine a determination of the glycosaminoglycans ( GAG). The excretion can be increased but only borderline or mild at the Sanfilippo syndrome. Therefore greater security, provides an electrophoresis, in which the increased excretion is reliably detected by heparan sulfate. If there is continuous suspicion the diagnosis (leukocytes) or fibroblasts can be secured by the determination of enzyme activities in white blood cells.

Therapy

Since it is a hereditary disease in Sanfilippo syndrome, no causal treatment is possible. Gene therapy is, however, at least for mucopolysaccharidosis type II ( Hurler ) already in clinical testing in humans. In some types of mucopolysaccharidoses, under certain circumstances, a bone marrow transplant to mitigate the progression of the disease, in particular if it is performed before the occurrence of skeletal abnormalities. For Sanfilippo disease this is not recommended in principle. Nevertheless, there are few reports of a decreased level of disability after a bone marrow transplant even with this disease. An enzyme replacement therapy, as it is already approved for other types of mucopolysaccharidoses, also does not exist for the type III. Symptomatic of the hyperactivity and insomnia can be treated with medication. However, each child reacts differently to different medications and they can after a certain time its effect again lose, so that individual treatment must be found for each patient. With markedly overactive and aggressive behavior have adequate protection in the home environment are needed to ensure that the children do not injure themselves. If dysphagia to be necessary for a transition to mushy food and feeding via a nasogastric tube. With increasing loss of ability to walk, this could lead to stiffening of the joints. This can be prevented by physiotherapy.

History

The disease was first described in 1963 by the physician Dr. Sanfilippo and his group. This is also where the name Sanfilippo.

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