Clinical polymorphism of storage diseases: A diferential diagnostic algorithm

The article presents an overview of the current understanding of lysosomal storage diseases (LSD) – a group of rare genetic disorders characterized by abnormal accumulation of macromolecular degradation products within cell organelles. The clinical manifestations of LSD vary significantly depending on the type of disorder and may include liver damage, neurological symptoms, and involvement of other organs. To illustrate the unique features of clinical course and mechanisms of liver injury associated with different types of LSD, individual nosologies have been reviewed, including Gaucher’s disease, Niemann-Pick disease, lysosomal acid lipase deficiency, gangliosidoses, and mucopolysaccharidoses, all of which show substantial differences in their pathogenesis and clinical presentations. Diagnostic criteria were described, focusing on measurements of enzyme activities and identification of pathogenic genotypes, alongside specialized biomarkers utilized for confirming diagnoses. Diagnosis of LSDs relies on assessing enzyme activity or metabolite concentrations in biological samples, while molecular-genetic testing is employed to verify the diagnosis. In this review, various therapeutic strategies are discussed, encompassing enzyme replacement therapy (ERT), substrate reduction therapy, and liver transplantation when severe organ involvement occurs. Early detection and prompt initiation of treatment are emphasized as crucial steps to prevent irreversible organ damage. Additionally, the prospects of applying gene therapy, which has shown positive outcomes in experimental studies, are highlighted. This approach opens up new possibilities for innovative treatments aimed at restoring normal enzyme function and preventing disease progression. The presented data offer a comprehensive insight into the issues surrounding the diagnosis and management of LSDs, which is important for both clinicians and researchers engaged in the study of rare diseases.

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