The Sanfilippo Syndrome is a rare congenital, hereditary -related metabolic disease . It belongs to the mucopolysaccharidoses , a group of disorders in the breakdown of long-chain sugar molecules, the glycosaminoglycans . The type III of mucopolysaccharidoses, which in turn is divided into four subtypes (A – D), is called Sanfilippo's syndrome. Affected children are still normal at birth. From the age of two to four, mental development is delayed. In some cases, skills that have already been learned decline. The children show extremely restless behavior ( hyperactivity ). In around the second decade of life, the behavioral disorder takes a back seat and is replaced by increasing spastic paralysis. In contrast to the other mucopolysaccharidoses, organs other than the brain are less affected. For example, the patients are usually of normal stature and have few skeletal abnormalities. There is no causal therapy, so the treatment is purely symptom-related.
|N -sulfoglucosamine sulfohydrolase (SGSH)
|N -alpha-acetylglucosaminidase (NAGLU)
|Heparan-alpha-glucosaminide N -acetyltransferase (HGSNAT)
|N -acetylglucosamine-6-sulfatase (GNS)
The undegraded heparan sulfate is stored in small functional sub-units of the cells ( organelles ), the lysosomes , which are enclosed by their own membrane ( lysosomal storage disease ). As nerve cells become increasingly overloaded, their functionality is increasingly disturbed and the corresponding symptoms occur. The storage of heparan sulfate in the bones and other organs is not so pronounced, so that these organs are not affected as badly in contrast to other mucopolysaccharidoses.
At birth, the children are completely normal. Due to the rarity of the disease, there are only a few studies on the natural course of symptoms. If the course is pronounced, children are increasingly lagging behind in their development from the age of two to four. They develop noticeably restless, overactive and possibly aggressive, destructive behavior. In this phase, those affected have pronounced sleep disorders. The children speak less and less and also gradually lose their understanding of the language. Later on, there are increasing symptoms of paralysis. Those affected eventually lose the ability to walk completely due to spastic paralysis. In addition, there are swallowing disorders, which increasingly lead to difficulties in nutrition. Epilepsy can also be an expression of the increasing disturbance of brain function.
A study from 2010 came to the conclusion that in almost 80% of those affected, the course was much weaker and the decline in intellectual abilities was only slight. Essentially, these children can reach adulthood without much limitation.
Compared to the symptoms on the part of the nervous system, the symptoms of the disease in other organs are less pronounced than in the other mucopolysaccharidoses: the body length reaches almost normal dimensions, the facial features are only somewhat coarsened with pronounced degradation of the brain function. Only the hair is noticeably thick and brittle. The eyebrows are also so bushy that they sometimes grow together in the middle. The course is very variable, depending on the severity, the majority of patients die in the second or third decade of life.
If the presence of Sanfilippo syndrome is suspected, the glycosaminoglycans (GAG) in the urine can first be determined . However, the excretion can only be marginally or slightly increased in Sanfilippo syndrome. Electrophoresis , in which the increased excretion of heparan sulfate is reliably detected, therefore offers greater security . If the suspicion persists, the diagnosis can be confirmed by determining the enzyme activities in white blood cells ( leukocytes ) or fibroblasts .
Since Sanfilippo syndrome is a hereditary disease, no causal treatment has been possible so far. In July 2014, a study was started at the UKE in Hamburg in which the first child (3 years old) in Germany is treated for the first time with the new enzyme replacement therapy for MPS IIIa. At the same time, this treatment was started at several European university hospitals.
A gene therapy for mucopolysaccharidosis type II (Hurler) is already in clinical trials in humans and a study is currently being prepared, which is expected to start in Barcelona in summer 2015. For some forms of mucopolysaccharidosis, a bone marrow transplant can, under certain circumstances, reduce the course of the disease, especially if it is done before the skeletal changes occur. In principle, this is not recommended for Sanfilippo syndrome. However, there have been individual reports of a reduced degree of disability after a bone marrow transplant, even with this disease. An approved enzyme replacement therapy, as it is already approved for other types of mucopolysaccharidoses, also does not yet exist for type III. Symptomatic hyperactivity and sleep disorders can be treated with medication. However, every child reacts differently to the various drugs and these can lose their effect again after a certain time, so that an individual treatment must be found for each patient. In the case of pronounced overactive and aggressive behavior, appropriate protective measures are necessary in the home environment so that the children do not injure themselves. If swallowing problems occur, nutrition via a gastric tube may be necessary after switching to a pulpy diet. With increasing loss of the ability to walk, the joints may become more rigid. This can be prevented with physiotherapy .
The disease was first described in 1963 by the American biochemist and pediatrician Sylvester Sanfilippo and his group, and was subsequently named after him.
Diseases in animals
- Marlies J. Valstar et al .: Mucopolysaccharidosis type IIIB may predominantly present with an attenuated clinical phenotype , J Inherit Metab Dis (2010) 33: 759-767 doi : 10.1007 / s10545-010-9199-y
- Cognitive development in patients with Mucopolysaccharidosis type III (Sanfilippo syndrome) PMC 3130633 (free full text)
- Johannes Zschocke, Georg F. Hoffmann: Vademecum metabolicum. 3. Edition. Schattauer, 2004, ISBN 3-7945-2375-X .
- A. Vellodi et al: Bone marrow transplantation for Sanfilippo disease type B. In: J Inherit Metab Dis. 1992, 15, pp. 911-918. PMID 1293388
- Margret L. Casal: Hereditary diseases. In: Peter S. Suter and Barbara Kohn: Internship at the dog clinic. 10th edition, Paul Parey, Stuttgart 2006, ISBN 978-3-8304-4141-0 , p. 194.