Enzymersatztherapie bei angeborenen Stoffwechselerkrankungen

Zusammenfassung

Angeborene Stoffwechselerkrankungen können sowohl nach den biochemischen Funktionsstörungen als auch nach der zellulären Lokalisation eingeteilt werden. Störungen in den Lysosomen werden als lysosomale Stoffwechselerkrankungen bezeichnet. Dabei sind seit langem Speichererkrankungen wie M. Gaucher, M. Fabry oder Mucopolysaccharidosen bekannt. Im Verlauf der letzten Jahrzehnte hat sich ein zunehmendes Wissen über die Pathologie lysosomaler Speichererkrankungen ergeben. Genetische Hintergründe, Enzymdefekte und Therapiemöglichkeiten wurden aufgedeckt. Nach anfänglicher Isolierung von Enzymen aus menschlichen und tierischen Zellen gelangen spezifische Modifizierungen der nun rekombinant herstellbaren humanen Enzyme zur Enzymersatztherapie (ERT). Im Folgenden sollen häufigere Speichererkrankungen vorstellt werden, das diagnostische Prozedere bei Verdacht auf lysosomale Stoffwechselerkrankungen erklärt und auf mögliche Therapieformen eingegangen werden. Schwerpunktmäßig soll dabei auf die Enzymersatztherapie, vor allem bei den schon länger behandelbar gewordenen Erkrankungen M. Gaucher, M. Fabry und Mukopolysaccharidose Typ 1 (Hurler/Scheie), besonderes Augenmerk gelegt werden.

Summary

Inborn errors of metabolism might be classified according to the underlying biochemical dysfunction or their cellular localisation. Disorders within the lysosomes are called lysosomal storage diseases. Diseases of this kind have been known since long, such as M. Gaucher, M. Fabry and mucopolysaccharidoses. Knowledge about the pathophysiology of lysosomal storage diseases has increased steadily in the course of the last centuries. Thus genetic backgrounds, enzymatic defects and therapeutic options have been revealed. Initially enzymes were isolated from human and animal cells, now specifically modified recombinant human enzymes are being used for enzyme replacement therapy (ERT). In the following common lysosomal storage diseases, diagnostic procedures in case of suspicion of such diseases and therapeutic possibilities are presented. The main focus will be on enzyme replacement therapy, mainly of the since some time already treatable disorders M. Gaucher, M. Fabry and mucopolysaccharidosis type 1 (Hurler/Scheie).

Schlüsselwörter

Angeborene Stoffwechselerkrankungen - lysosomale Speichererkrankungen - Mucopolysaccharidosen - M. Gaucher - M. Fabry - Enzymersatztherapie

Keywords

Inborn errors of metabolism - lysosomal storage diseases - mucopolysaccharidoses - M. Gaucher - M. Fabry - enzyme replacement therapy

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