Mucopolysaccharidosis

MPS genetic defect: “sugar waste” destroys the cells

In mucopolysaccharidosis, those affected lack an enzyme, which means that complex sugar chains cannot be completely broken down.

(Bild: jijomathai/stock.adobe.com)

Mucopolysaccharidosis (MPS for short) refers to a group of congenital, slowly progressive metabolic diseases. Due to a missing enzyme, complex sugar molecules are not broken down, accumulate in harmful quantities in the cells and destroy them. Early treatment can improve the life expectancy and quality of life of affected children.  

Mucopolysaccharides are long, also branched, sugar chains (polysaccharides) that are found everywhere in the body. They are an important component of connective tissue and ensure, for example, the firmness of tissue and organs, the water balance and the interaction between cells. They are constantly being formed, broken down and broken down again with the help of enzymes. This is a complex process.

In MPS patients, one of these enzymes is missing, so that the breakdown of the sugar chains is blocked and undigested residues of material accumulate until the cells are destroyed and the organs lose their function. Depending on which of these eleven enzymes is affected, the symptoms of MPS can vary greatly.

Mukopolysaccharide bestehen aus Ketten von speziellen Zuckermolekülen. Sie sind wichtiger Bestandteil des Bindegewebes, kommen überall im Körper vor und spielen eine wichtige Rolle in der Steuerung von Zellfunktionen.

Die Zuckermoleküle werden ständig neu gebildet und in speziellen „Schrottplätzen“ (den Lysosomen) in den Zellen wieder abgebaut. Dazu sind spezielle „Schraubenschlüssel“ notwendig – die Enzyme.

Von einem Ende her werden die Kettenmoleküle Stück für Stück zerlegt. Jeder Baustein kann nur mit einem für ihn passenden Spezialschlüssel (= einem speziellen Enzym) freigesetzt werden. Elf verschiedene Enzyme sind notwendig, die jeweils nacheinander die Zuckerketten verkleinern, bis schließlich einfachste Bestandteile übrigbleiben, die durch die Zellmembran geschleust und dann vom Körper verwertet oder ausgeschieden werden.

Bei den Mukopolysaccharidosen ist durch einen erblichen Fehler ein Schlüssel kaputt (d.h. ein Enzym funktioniert nicht richtig). Der Abbau kommt zum Stillstand und die halb zerkleinerten Ketten bleiben in den Lysosomen der Zelle liegen. 

Die Ansammlung der halb abgebauten Mokopolysaccharide führt zum Anschwellen der Lysosomen, zur Schädigung der Zellen und zu Veränderungen in jenen Organen, in denen die Mukopolysaccharide besonders wichtig sind: Gehirn, Leber, Milz, Haut und Skelett.

The symptoms of the various forms of MPS range from bone changes to functional impairments of internal organs such as the heart and liver to severe brain disorders. Some children become blind, most are hard of hearing and short in stature. The average life expectancy of an untreated MPS child is 15 years.

Even though there is still no cure for MPS, there are now therapies for some forms that have a positive influence on the course of the disease. The effectiveness depends on starting treatment at an early stage. This is because existing damage can no longer be reversed. 

Enjoying life: Affected person at the MPS therapy week of the self-help association "MPS Austria".

(Bild: Johannes Weigl Fotografie )

As children develop inconspicuously in the very first months of life, it takes the experience of a trained paediatrician or general practitioner to recognize the early symptoms. Individually, these are usually non-specific, but in combination they are often an indication of this genetic defect. These include a relatively large head, a short neck, slower development, stiff finger joints, frequent infections, middle ear infections and inguinal and umbilical hernias.

Different clinical pictures
Some patients show typical accumulation of "metabolic waste" in all organs, with greatly enlarged liver and spleen, thickening of the heart wall and thickened skin and mucous membranes. Others show deformed bones, short stature, slack tendons and ligaments. However, physical changes are not always apparent.

Sometimes behavioral abnormalities are in the foreground. The children are then considered "difficult" because they are very restless, restless, almost aggressive, hardly speak or gradually unlearn all the skills they had already acquired. They later become increasingly apathetic until they are finally completely unable to move. It often takes years for patients to finally receive the correct diagnosis after countless visits to the doctor. 

Jeder kann mitmachen

Unterstützung für Betroffene

Gemma MPS-Online Challenge der österreichischen MPS-Gesellschaft von 15. Mai (internationaler MPS-Tag) bis 15. Juni:  
6815 Aminosäuren sind für die verschiedenen Typen der Stoffwechselerkrankung MPS verantwortlich. Und genau so viele Minuten in Bewegung sollen gesammelt werden (z.B. Spaziergang mit dem Hund, Tanzen, Volleyball, Radfahren etc.), egal ob allein, mit der Familie oder im Team. Außerdem ist ein großes Ziel des Selbsthilfevereins, Spenden in Höhe von 6.815 Euro zu sammeln. 

Weitere Infos:  Gesellschaft für Mukopolysaccharidosen 
Tel: + 43-7249-47795, Mail: [e-mail]
Spendenkonto: Erste Bank: AT89 2011 1847 2581 7800

New therapies bring hope
For around half of MPS forms, there are now therapies that have a positive influence on the course of the disease. Such as bone marrow transplants, especially if they are carried out by the end of the second year of life. Enzyme replacement therapy is also effective in many forms. The missing enzyme is produced artificially in cell cultures and administered to the patient at regular intervals by infusion. Great expectations are placed on gene therapies, which are already being intensively researched in order to change the DNA in such a way that a healthy enzyme is produced. 

Depending on the severity of the disease, there are also a variety of treatment options available to improve the symptoms. These include orthopaedic or neurological therapies as well as support for eye or ENT problems.

However, early diagnosis is not only important so that appropriate treatment can be initiated quickly for the affected child. As MPS is a hereditary metabolic disease, there is a significant risk that future siblings will also be affected. 

Genetic defect is hereditary
Everyone carries genetic defects, but it is not possible to predict which ones they are and the disease does not always occur. Mucopolysaccharidoses are passed on from healthy carriers to their children through a genetic change in the chromosomes. However, the child usually only develops the disease if both parents have the same defect for the same enzyme and pass it on to the child with their genes.

If parents have defective genes for different enzymes or if only one diseased gene is passed on, then the children are just as healthy as their parents. However, there is then a certain risk that they will in turn be carriers and have an MPS child themselves if their partner happens to carry the same genetic defect.