Ultrastructural deposits appearing as "zebra bodies" in renal biopsy: Fabry disease?- comparative case reports

Abstract

Background: Fabry Disease (FD) is a genetic disorder caused by alpha-galactosidase A deficiency. Certain drugs, such as hydroxychloroquine, can produce renal deposits that mimic morphological findings seen in FD, characterizing a type of drug-induced renal phospholipidosis.

Case presentation: Case 1: A 28-year-old female patient with systemic lupus erythematosus who had been using hydroxychloroquine for 14 months presented subnephrotic proteinuria. Renal biopsy showed deposits compatible with FD. Neither activity analysis of alpha-galactosidase A nor genetic analysis were available and were not performed. These deposits were not detected in a subsequent renal biopsy three years after withdrawal of the medication, characterizing a possible hydroxychloroquine-induced renal phospholipidosis. Case 2: A 29-year-old male patient presented with acroparesthesia, angiokeratomas, cornea verticillata and subnephrotic proteinuria. Deposits compatible with FD were detected upon renal biopsy. The evaluation of alpha-galactosidase A showed no activity in both blood and leukocytes. Genetic analysis identified an M284 T mutation in exon 6, and such mutation was also found in other family members.

Conclusion: Clinical investigation is necessary in suspected cases of Fabry Disease upon renal biopsy in order to confirm diagnosis. Drug-induced renal phospholipidosis should be considered in differential diagnosis in cases with intracellular osmiophilic, lamellar inclusions in electron microscopy.

Keywords: Fabry Disease; Hydroxychloroquine; Lysosomal Storage Disorder; Renal Biopsy; Systemic Lupus Erythematosus.

Fig. 1

Electron microscopy: Case 1 - first biopsy (a and b): intralysosomal, osmiophilic, lamellated and sometimes concentric inclusions in the cytoplasm of podocytes (black arrows) resembling or “zebra bodies”. Case 1 – second biopsy (c, d and e): podocytes presented cytoplasmatic swelling (arrow heads), sometimes forming optically empty vacuoles (slim black arrows) and there are some podocyte foot process effacement (white arrows). The lipid deposits seen in the previous biopsy were no longer detected. Case 2 - (f, g and h): deposits of lamellate, lipid-like, electron-dense material forming concentric bodies, “zebra bodies” in the cytoplasm of podocytes (black arrows) (f, h) and endothelial cells in both glomerular (white arrow head) (f) and peritubular capillaries (white slim arrows) (g).Image magnifications are specified in each lower border