Hydroxychloroquine-induced podocytopathy mimicking Fabry disease

Serre, Justine; Buob, David; Boffa, Jean‐Jacques

doi:10.1136/bcr-2018-228876

Cited by 18 publications

(24 citation statements)

References 12 publications

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“…In this respect, the renal involvement of this patient is both highly suggestive of FD (vacuolisation with pseudomyelinic bodies) and atypical (additional IgA mesangial deposits). The patient had never been treated with medications associated with pseudomyelinic inclusions (such as antimalarials) [16][17][18][19] or with lyso-Gb3 elevation (such as amiodarone) [19].…”

Section: Discussionmentioning

confidence: 99%

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease

Greillier¹,

Daniel

Caillaud

et al. 2020

BMC Med Genet

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Background: Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes. Case presentation: The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes' lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography. Conclusions: We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.

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Section: Discussionmentioning

confidence: 99%

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease

Greillier¹,

Daniel

Caillaud

et al. 2020

BMC Med Genet

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“…Other known causes for similar findings include hydroxychloroquine, which, by causing phospholipidosis, can mimic zebra bodies, and be mistaken for Fabry's disease. This was evident in multiple case reports [18,19,20]. Our patient was not taking hydroxychloroquine; and for the donor's privacy we could not pursue further information about the donor nor her family.…”

Section: Biopsymentioning

confidence: 93%

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

Abuzeineh

Ziadeh

Kheradmand³

et al. 2020

CNCS

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Detection of donor-specific antibodies (DSA) is an essential part of diagnosing antibody-mediated renal allograft rejection (ABMR). The role of solitary preformed, or post-transplant HLA-C antigens in solid organ transplantation is unclear, due to the less sensitive nature of the historical assays, lack of data, low expression level on the cell surface, and their coexistence with other anti-HLA DSA. Herein, we present the case of a 39-year-old African American man, without prior history of pre-transplant sensitization that was diagnosed with biopsyproven ABMR due to de novo donor-specific anti-HLA-C antibodies. This case report illustrates the role of HLA-C antibodies in causing ABMR if generated toward immunogenic-shared epitopes and demonstrates the need for their recognition in the pre-and post-transplant period. Another interesting aspect of this case is the incidental finding of Fabry-like zebra bodies, which we eventually determined to be of unclear etiology.

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“…The lysosome inhibitor hydroxychloroquine is recommended for the management of autoimmune diseases, including lupus, and has been shown to protect against AKI in mice by suppressing NLRP3 inflammasome activation [83]. However, in rare cases, hydroxychloroquine accumulates in lysosomes and induces cytoplasmic vacuolization and zebra bodies in podocytes, which are mimicking the histological lesions of Fabry's disease and ultimately resulting in podocyte injury and proteinuria [84,85].…”

Section: Drug-and Heavy Metal-induced Renal Damagementioning

confidence: 99%

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury

Chen

Yang

et al. 2021

Kidney Dis

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Background: Macroautophagy (autophagy) is a cellular recycling process involving the destruction of damaged organelles and proteins in intracellular lysosomes for efficient nutrient reuse. Summary: Impairment of the autophagy-lysosome pathway is tightly associated with multiple kidney diseases, such as diabetic nephropathy, proteinuric kidney disease, acute kidney injury, crystalline nephropathy, and drug- and heavy metal-induced renal injury. The impairment in the process of autophagic clearance may induce injury in renal intrinsic cells by activating the inflammasome, inducing cell cycle arrest, and cell death. The lysosome depletion may be a key mechanism triggering this process. In this review, we discuss this pathway and summarize the protective mechanisms for restoration of lysosome function and autophagic flux via the endosomal sorting complex required for transport (ESCRT) machinery, lysophagy, and transcription factor EB-mediated lysosome biogenesis. Key Message: Further exploring mechanisms of ESCRT, lysophagy, and lysosome biogenesis may provide novel therapy strategies for the management of kidney diseases.

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Hydroxychloroquine-induced podocytopathy mimicking Fabry disease

Cited by 18 publications

References 12 publications

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease

First phenotypic description of a female patient with c.610 T > C variant of GLA: a renal-predominant presentation of Fabry disease

A curious case of de novo anti-HLA-C antibody-mediated humoral rejection and Fabry-like zebra bodies in a renal transplant recipient

Lysosome Depletion-Triggered Autophagy Impairment in Progressive Kidney Injury

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