Screening for Fabry Disease in Kidney Transplant Recipients: Experience of a Multidisciplinary Team.

Massimiliano Veroux,Antonio Basile,Ines Monte,Concetta De Pasquale,Rita Bella,Daniela Corona,Giuseppe Lanza,Stefano Palmucci,Pierfrancesco Veroux,Maria Pistorio,Margherita Rodolico

doi:10.3390/biomedicines8100396

Abstract

Fabry disease (FD) is a rare cause of end-stage renal disease requiring kidney transplantation. Data on the incidence of unrecognized FD in kidney transplant recipients are scarce and probably underestimated. This study evaluated the incidence of FD in a population of kidney recipients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach. Two hundred sixty-five kidney transplant recipients were screened with a genetic analysis for α-galactosidase A (GLA) mutation, with measurement of α-Gal A enzyme activity and Lyso Gb3 levels. Screening was also extended to relatives of affected patients. Seven patients (2.6%) had a GLA mutation. Two patients had a classic form of FD with Fabry nephropathy. Among the relatives, 15 subjects had a GLA mutation, and two had a Fabry nephropathy. The clinical and diagnostic assessment was completed after a median of 3.2 months, and mean time from diagnosis to treatment was 4.6 months. This study reported a high incidence of unrecognized GLA mutations in kidney transplant recipients. Evaluation and management by a multidisciplinary team allowed for an early diagnosis and treatment, and this would result in a delay in the progression of the disease and, finally, in better long-term outcomes.

Highlights

Fabry disease (FD) is a rare X-linked lysosomal storage disorder, caused by deficiency of the enzyme α-galactosidase A (GLA), resulting in an accumulation of globotriaosylceramide in tissues, mainly heart, brain and kidney, leading to progressive organ dysfunction [1]
The Fabry multidisciplinary team of the University Hospital of Catania included more than 30 specialists with specific expertise on Fabry disease, which are actively involved in the diagnosis and management of potential FD patients, with the aim to significantly reduce the time to diagnosis and treatment
Microalbuminuria and proteinuria are present in a high proportion of patients with FD [17] and after the fifth decade of life the evolution toward end-stage renal disease (ESRD) is frequent among this population [17]

Summary

Introduction

Fabry disease (FD) is a rare X-linked lysosomal storage disorder, caused by deficiency of the enzyme α-galactosidase A (GLA), resulting in an accumulation of globotriaosylceramide in tissues, mainly heart, brain and kidney, leading to progressive organ dysfunction [1]. Kidney transplantation represents the best replacement therapy for patients with end-stage renal disease [18] and is a recommended therapeutic option even for patients with Fabry nephropathy [15]. A recent review of screening studies performed in the period 1995–2017 [14] found a prevalence of 0.2–0.4% of FD among female transplant recipients and an incidence 0.38–1.12% among male patients. We investigated the incidence of unrecognized Fabry disease in a population of kidney transplant recipients performed at a single institution, with the extension of screening to the relatives of the affected patients, with a particular focus of the multidisciplinary approach for an early clinical assessment and therapeutic approach

Study Population

Clinical Assessment

Results

Discussion