Inborn Errors of Metabolism (IEM) are a group of genetically determined hereditary diseases in which an enzymatic or transport defect leads to blockage of a metabolic pathway. Included in this category are the Lysosomal Storage Diseases (LSD), characterized by a disturbance in lysosomal homeostasis, whose protein deficiency causes abnormal accumulation of macromolecules. These disorders present a variety of symptoms, but all permanent and progressive. The majority of LSD presents monogenic autosomal recessive inheritance, as Gaucher and Pompe disease, or X-linked pattern of inheritance, as Fabry disease (FD). FD is caused by a mutation in GLA gene, which results in a deficiency of the enzyme alpha-galactosidase A and accumulation of globotriaosylceramide (Gb3). The abnormal storage of Gb3 occurs inside the lysosomes and is manifested in various tissues such as skin, eyes, kidney, heart, brain and peripheral nervous system. In previous experiments performed by our group, it was observed that the cell growth of fibroblasts from patients with Fabry Disease was slower compared to control (unpublished data); suggesting that the cell cycle control of these cells might be involved in the differences observed. Several studies show the influence of circadian rhythms in physiological processes and gene expression, as well as its impact on the regulatory mechanisms of cell cycle. Thus, this project aims to investigate the correlation between cell cycle and circadian rhythms in cell cultures of Fabry Disease patients.
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