Suvremeni pogled na lizosomske bolesti nakupljanja. (Croatian)

Lysosomal storage disorders: a modern perspective. (English)

Lysosomal storage disorders comprise a group of about 70 hereditary diseases that arise due to lysosome dysfunction and the consequent accumulation of substrates that initiates secondary pathological processes. Clinical presentation is very heterogeneous and depends on the type of disorder and residual enzyme activity. Most of disorders are progressive and multisystem diseases, often with a neurodegenerative course. Although individual diseases are very rare, the overall incidence of lysosomal disorders is about 1:5000 live births. Along with hematopoietic stem cell transplantation, which was the first etiological therapy, during the last 30 years, enzyme replacement therapy and other types of pharmacological treatment have gradually become available for numerous lysosomal storage diseases. However, despite the significant development of therapeutic options, there is still no specific treatment for many lysosmal disorders. In addition, there is the need for additional improvements of existing and development of new therapies for treatable diseases, with the goal to improve the patient outcomes. Novel scientific knowledge about the roles of lysosomes in the control of various cellular metabolic processes and the complex pathogenesis of lysosomal storage diseases is crucial for the development of new and more efficient therapeutic approaches. In the recent years, we are witnessing development of gene therapy and the beginning of its application in certain lysosomal diseases. Due to the significant delay between the symptom onset and established diagnosis, which leads to poorer therapeutic efficiency, some treatable diseases from this group have been introduced into the newborn screening programs in several countries. Along with a brief reminder of the clinical signs of lysosomal storage diseases, clues when to suspect and how to diagnose them, we will briefly review the current therapeutic options. [ABSTRACT FROM AUTHOR]

Lizosomske bolesti nakupljanja su skupina od oko sedamdeset nasljednih bolesti koje nastaju zbog disfunkcije lizosoma i posljedičnog nakupljanja supstrata te pokretanja sekundarnih patoloških procesa. Klinička slika je vrlo heterogena, a ovisi o vrsti poremećaja i ostatnoj funkciji enzima/proteina. Većinom su to progresivne i multisistemske bolesti, često neurodegenerativnog tijeka. Iako su pojedinačno vrlo rijetke, ukupna incidencija je relativno visoka i iznosi 1:5.000 živorođenih. Uz transplantaciju matičnih hematopoetskih stanica koja je bila prva etiološka terapija za liječenje nekih lizosomskih bolesti, zadnjih trideset godina postupno su za brojne bolesti iz ove skupine postale dostupne enzimska nadomjesna terapija i druge vrste farmakološke terapije. Međutim, usprkos značajnom razvoju terapijskih mogućnosti, za većinu ovih bolesti do danas nema specifičnog liječenja. Uz to, pojavila se potreba za dodatnim poboljšanjima postojećih i razvojem novih terapijskih opcija, a sve s ciljem učinkovitijeg liječenja i poboljšanja ishoda bolesti. Novije znanstvene spoznaje o ulogama lizosoma u kontroli različitih staničnih metaboličkih procesa i složenoj patogenezi lizosomskih bolesti nakupljanja ključne su za razvoj novih i učinkovitijih terapijskih pristupa. Zadnjih godina u velikom je zamahu razvoj genske terapije i danas smo svjedoci započinjanja njezine primjene u pojedinim lizosomskim bolestima. Zbog značajnog kašnjenja u postavljanju dijagnoze i posljedično lošijih terapijskih ishoda, u više zemalja neke liječive bolesti iz ove skupine uvedene su u programe novorođenačkog probira. Uz kratki podsjetnik na kliničku sliku lizosomskih bolesti nakupljanja, naputke kada posumnjati na ove bolesti i koje dijagnostičke alate koristiti, kratko ćemo se osvrnuti i na trenutne terapijske mogućnosti. [ABSTRACT FROM AUTHOR]

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