The origin of urinary mulberry cells in Fabry disease

Yokoyama, Takashi; Manabe, Shun; Horita, Shigeru; Kataoka, Hiroshi; Mochizuki, Toshio; Nitta, Kosaku

doi:10.1016/j.kint.2020.08.019

Cited by 2 publications

(2 citation statements)

References 22 publications

(29 reference statements)

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“…Multiple atypical variants predominantly involve one organ, with significant residual enzyme activity. The most frequently targeted organs include the kidneys [ 4 , 5 ], heart [ 6 , 7 ], peripheral nerves, and skin. Diagnosis of these variants is difficult, as there is no clear correlation between genotype and phenotype [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease

Li,

Xi,

Zhang

et al. 2024

Cells

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Fabry disease (FD) is an X-linked recessive inheritance lysosomal storage disorder caused by pathogenic mutations in the GLA gene leading to a deficiency of the enzyme alpha-galactosidase A (α-Gal A). Multiple organ systems are implicated in FD, most notably the kidney, heart, and central nervous system. In our previous study, we identified four GLA mutations from four independent Fabry disease families with kidney disease or neuropathic pain: c.119C>A (p.P40H), c.280T>C (C94R), c.680G>C (p.R227P) and c.801+1G>A (p.L268fsX3). To reveal the molecular mechanism underlying the predisposition to Fabry disease caused by GLA mutations, we analyzed the effects of these four GLA mutations on the protein structure of α-galactosidase A using bioinformatics methods. The results showed that these mutations have a significant impact on the internal dynamics and structures of GLA, and all these altered amino acids are close to the enzyme activity center and lead to significantly reduced enzyme activity. Furthermore, these mutations led to the accumulation of autophagosomes and impairment of autophagy in the cells, which may in turn negatively regulate autophagy by slightly increasing the phosphorylation of mTOR. Moreover, the overexpression of these GLA mutants promoted the expression of lysosome-associated membrane protein 2 (LAMP2), resulting in an increased number of lysosomes. Our study reveals the pathogenesis of these four GLA mutations in FD and provides a scientific foundation for accurate diagnosis and precise medical intervention for FD.

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Section: Introductionmentioning

confidence: 99%

GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease

Li,

Xi,

Zhang

et al. 2024

Cells

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“…Regarding renal involvement, podocytopathy-mediated proteinuria, rather than tubular dysfunction, is considered the main pathology related to the renal prognosis (5)(6)(7). The only effective treatment for Fabry disease is enzyme replacement therapy (ERT) with recombinant human GLA (8)(9)(10). No treatment has been established for patients with ERT-resistant proteinuria to date.…”

Section: Introductionmentioning

confidence: 99%

Improvement in Decline Rate of Estimated Glomerular Filtration Rate after Febuxostat Treatment in a Fabry Disease Patient with Enzyme Replacement Therapy-resistant Proteinuria

et al. 2022

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Fabry disease is an inherited lysosomal disorder caused by mutations in the alpha-galactosidase A gene. We herein report a Fabry disease patient with enzyme replacement therapy (ERT)-resistant proteinuria who showed improvement in the estimated glomerular filtration rate (eGFR) decline rate after uric acid (UA)lowering therapy. The patient was diagnosed with Fabry disease at 36 years old. After that, even under ERT, proteinuria and eGFR decline persisted. During the clinical course, serum UA levels were elevated with increases in renal tubular damage markers. Febuxostat administration immediately improved tubular damage and prevented further eGFR decline. UA-mediated tubulopathy may become an additional therapeutic target for eGFR decline in Fabry disease.

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The origin of urinary mulberry cells in Fabry disease

Cited by 2 publications

References 22 publications

GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease

GLA Mutations Suppress Autophagy and Stimulate Lysosome Generation in Fabry Disease

Improvement in Decline Rate of Estimated Glomerular Filtration Rate after Febuxostat Treatment in a Fabry Disease Patient with Enzyme Replacement Therapy-resistant Proteinuria

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