A case of latent heterozygous Fabry disease in a female living kidney donor candidate

Abstract

A 52-year-old woman had been found to have hematuria at her annual checkup 5 years in a row. She hoped to donate her kidney to her husband, so we performed a percutaneous kidney biopsy at our department. It was difficult for us to detect apparent abnormalities under a light microscopic examination, and she was determined to meet the eligibility criteria for living kidney transplantation. However, the sample for electron microscopy was not evaluated before kidney donation. She subsequently underwent living kidney transplantation as a donor. A 1-h biopsy revealed swelling and obvious vacuolation of the glomerular podocytes, which were characteristic of Fabry disease. Her medical history and examinations were reviewed. No findings or episodes were observed. Pre-donation electronmicroscopy revealed numerous zebra bodies in the podocytes. A definite diagnosis of heterozygous Fabry disease was made based on the GLA gene mutation despite the normal range of leukocyte α-Gal A activity. Based on the pathological deposition of GL-3, chaperone therapy was initiated to suppress the progression of organ damage. In this case, we could not confirm a diagnosis of Fabry disease despite performing a renal biopsy prior to kidney donation. Kidney donor candidates may sometimes have factors that cannot be assumed based on medical or family history. Thus, it is important to perform a renal biopsy before kidney donation when necessary, and to always conduct a detailed evaluation including electron microscopy.

Keywords: Chaperone therapy; GLA gene mutation; Heterozygous Fabry disease; Kidney transplantation; Migalastat; α-Galactosidase A.

Fig. 1

a, c, d Renal pathology prior to kidney donation; b a 1-h biopsy. a No apparent change was detected in the glomeruli under a light microscopic examination before kidney donation (PAS staining × 400). b A 1-h biopsy revealed remarkable swelling and obvious vacuolation of the glomerular podocytes (PAS staining × 400). c Pre-donation electron microscopy revealed numerous zebra bodies in the podocytes (× 3000). d Basement membrane thinning (180 nm) was observed in part of the specimen (Arrowhead). Scale bars 2 μm