Author/Editor		Žerjav-Tanšek, M; Kitanovski, L; Benedik-Dolničar, M; Battelino, T
Title		Zdravljenje lizosomskih bolezni - sedanjost in prihodnost
Translated title		Treatment of lysosomal storage disease - present and future
Type		članek
Source		Slov Pediatr
Vol. and No.		Letnik 13, št. 1
Publication year		2006
Volume		str. 6-19
Language		slo
Abstract		There are more than 40 different forms of inherited lysosomal storage diseases (LSD) known to occur in humans and the aggregate incidence has been estimated to approach 1 in 7.000 to 8.000 live births. Deficient activity of any one of numerous lysosomal enzymes results in a specific lysosomal storage disorder, due to the progressme storage ot tne substrate in affected organs and tissues. Sphingolipidoses, mucopolysaccharidoses and oligosaccharidoses are the main groups of lysosomal diseases and despite a great variability they share some clinical manifestations. Most LSDs are associated with high morbidity and mortality and represent a significant burden on patients, their families, and health care providers. Except for symptomatic therapies, many LSDs remain untreatable. Animal models of LSDs play a critical role in evaluating the efficacy and safety of therapy for many of these conditions. Therapies for some LSDs do exist, or are under evaluation, including allogenic bone marrow transplantation, enzyme replacement therapy (ERT), and enzyme enhancement therapy. These treatment options are associated with significant concerns, including high morbidity and mortality with limited positive outcomes in bone marrow or hematopoietic stem cell transplantation, incomplete response to therapy and life-long therapy in ERT and high costs of therapies. ERT in Gaucher and Fabry disease is successful if the therapy is introduced early and with sufficient dosage. ERT in LSD is reviewed regarding history, biochemical features, efficiency in clinical studies and side effects. The other therapies for some LSDs are reviewed shortly.
Summary		Število lizosomskih bolezni (LB) pri človeku je ocenjeno na preko 40 različnih motenj delovanja posameznih lizosomskih encimov, zaradi katerih se nepresnovljen substrat kopiči v prizadetih organih in tkivih. Incidenca vseh LB je približno 1 na 7.000 do 8.000 živorojenih. Sfingolipidoze, mukopolisaharidoze in oligosaharidoze so glavne skupine LB. Čeprav so zelo različne, imajo nekatere skupne klinične značilnosti. Posledice bolezni so pogosto hude in smrtnost bolnikov je visoka, kar je veliko breme za bolnika in zdravstvo. Živalski modeli LB so pomembno prispevali k razvoju zdravljenja teh bolezni, čeprav večino bolezni še vedno zdravimo le simptomatsko. Usmerjeni načini zdravljenja so presaditev kostnega mozga, encimsko nadomestno zdravljenje (ENZ) in povečanje encimske aktivnosti s šaperoni. Presaditev kostnega mozga ali krvotvornih matičnih celic je še vedno povezana s številnimi zapleti ter omejenim uspehom zdravljenja. Učinkovitost ENZ omejujejo od odmerka odvisen in včasih nepopolen odgovor na zdravljenje, potrebnost doživljenjskega parenteralnega zdravljenja ter visoki stroški. Uspešnost ENZ je dobra pri Gaucherjevi in Fabryjevi bolezni, če je zdravljenje uvedeno dovolj zgodaj v primernem odmerku. Članek pregledno opisuje zdravljenje LB z ENZ, navedeni so biokemični in klinični podatki, učinkovitost ter stranski učinki zdravljenja. Kratko so predstavljene tudi druge oblike zdravljenja.
Descriptors		LYSOSOMAL STORAGE DISEASES SPHINGOLIPIDOSES MUCOPOLYSACCHARIDOSES OLIGOSACCHARIDES BONE MARROW TRANSPLANTATION HEMATOPOIETIC STEM CELL TRANSPLANTATION GAUCHER'S DISEASE FABRY'S DISEASE