Fabry Nephropathy: Indications for Screening and Guidance for Diagnosis and Treatment by the European Renal Best Practice

Wim Terryn; Pierre Cochat; Roseline Froissart; Alberto Ortiz; Yves Pirson; Bruce Poppe; Andreas Serra; Wim Van Biesen; Raymond Vanholder; Christoph Wanner


Nephrol Dial Transplant. 2013;28(3):505-517. 

In This Article

Abstract and Introduction


Fabry disease (FD) is an X-linked disorder of glycosphingolipid catabolism resulting in the accumulation of glycolipids including globotriaosylceramide in cells of various tissues resulting in end-organ manifestations. Initially, FD is typically characterized by angiokeratoma and recurrent episodes of neuropathic pain in the extremities occurring during childhood or adolescence. Most affected patients also exhibit a decreased ability to sweat. Later in life, FD results in left ventricular hypertrophy, proteinuria, renal failure and stroke. These later disease manifestations are non-specific and also common in diabetes, hypertension and atheromatosis and thus for most practitioners do not point into the direction of FD. As a consequence, FD is under-diagnosed and screening of high-risk groups is important for case finding, as is a thorough pedigree analysis of affected patients. In the nephrology clinic, we suggest to screen patients for FD when there is unexplained chronic kidney disease in males younger than 50 years and females of any age. In men, this can be performed by measuring α-galactosidase A activity in plasma, white blood cells or dried blood spots. In women, mutation analysis is necessary, as enzyme measurement alone could miss over one-third of female Fabry patients. A multidisciplinary team should closely monitor all known Fabry patients, with the nephrologist screening kidney impairment (glomerular filtration rate and proteinuria) on a regular basis. Transplanted Fabry patients have a higher mortality than the regular transplant population, but have acceptable outcomes, compared with Fabry patients remaining on dialysis. It is unclear whether enzyme replacement therapy (ERT) prevents deterioration of kidney function. In view of the lack of compelling evidence for ERT, and the low likelihood that a sufficiently powered randomized controlled trial on this topic will be performed, data of all patients with FD should be collected in a central registry.


European Renal Best Practice (ERBP) is the official guideline body of the European Renal Association/European Dialysis and Transplant Association (ERA/EDTA). The mission of ERBP is to improve the outcome of patients with kidney disease in a sustainable way, through enhancing the accessibility of knowledge on patient care, in a format that stimulates its use in clinical practice. In line with this mission, and in view of its philosophy,[1] the ERBP advisory board considered it useful to develop guidance in the field of orphan diseases with nephrological relevance. Typical for these diseases are the rather low patient number, and consequently, the lack of large trials. As a consequence, formal evidence-based medicine is nearly impossible in this field. Nevertheless, nephrologists need guidance on how to approach patients with these diseases. Therefore, ERBP decided to use the combination of formal systematic literature reviews, a consensus meeting with an international panel of experts and peer review as a suitable model to develop guidance in the field of orphan diseases. A first paper on oxalosis has already been published in this series.[2] This paper presents the results of a guidance process on the topic of Fabry disease (FD).

FD (OMIM ID #301500) is an X-linked inborn error of glycosphingolipid catabolism caused by quantitative or qualitative defects in the lysosomal enzyme α-galactosidase A (α-Gal A). As a result, glycosphingolipids, mainly globotriaosylceramide (Gb-3), accumulate in the lysosomes of different cells throughout the body, ultimately resulting in organ failure.[3,4] Patients with FD have a markedly limited life expectancy due to cardiovascular, neurological and renal involvement. Enzyme replacement therapy (ERT) has been made available since 2001. Intravenous infusion every other week results in the removal of a part of the Gb-3 deposits, diminishes Fabry-related symptoms and possibly protects organs to a certain extent.[5,6] The effects of ERT on progression of renal disease (proteinuria and renal function) are unclear.