Thematic Area:  

Fabry Disease

The following guidance documents have been endorsed by the Workgroup following standardized quality evaluation:

Fabry Nephropathy: Indications for screening and guidance for diagnosis and treatment by the European Renal Best Practice   

Nephrol Dial Transplant 2013; 28:505-517

Core Recommendations:
  1. We recommend screening for Fabry Disease in male CKD patients below 50 years of age in whom a reliable renal diagnosis is absent.
  2. We suggest screening for Fabry Disease in females with unexplained CKD, irrespective of age, with other unexplained symptoms potentially associated with Fabry Disease.
  3. We recommend discussing with the patient the implications of diagnosing a genetic disease and the possible implications for the at-risk relatives.
  4. We recommend using enzyme activity measurement for alpha-Gal A as a primary tool in males, followed by confirmation with mutation analysis when positive.
  5. We do not recommend starting enzyme replacement therapy in patients with proteinuria or eGFR <60 mL/min/1.73 m2, except for non-renal indications. 
  6. We recommend that when enzyme replacement therapy is deemed indicated, it should be started as part of a well-designed clinical trial, either observational or interventional.
Comments by Evaluators:
  • Slightly old but methodologically correct, with very clear recommendations 

Screening, diagnosis and management of patients with Fabry disease: Conclusions from a KDIGO Controversies Conference     

Kidney Int 2017; 91:284-293

Core Recommendations:
  1. The diagnosis is established in males by a-galactosidase A–specific activity below 25-30% of control in peripheral white blood cells.
  2. There is a wide phenotypic variability even among patients with the same GLA mutation.   
  3. FD should be considered and tested in patients with chronic kidney disease (CKD) with no definitive cause of nephropathy, especially in familial cases.
  4. Common standard-of-care therapies are highly effective in alleviating symptoms and treating disease complications. There is no scientific evidence as to the optimal age of enzyme replacement therapy (ERT) initiation.
  5. Development of signs or symptoms related to FD is an indication to start ERT. For the kidney, this implies the development of CKD. The benefits of early treatment, before irreversible tissue injury occurs, should be balanced against the burden of biweekly infusions in very young individuals. There is a suggestion that ERT slows the progression of kidney involvement and results in reduction of hypertrophic cardiomyopathy, especially when started prior to established fibrosis. However, there is no reduction in the rate of stroke with ERT.
Comments by Evaluators:
  • Authors are key opinion leaders; no external reviewers available due to large number of authors.

Recommendations for initiation and cessation of enzyme replacement therapy in patients with Fabry Disease:  the European Fabry Working Group consensus document   

Orphanet J Rare Dise 2015; 10:36

Core Recommendations:
  1. For classically affected males, enzyme replacement therapy (ERT) is recommended as soon as there are early clinical signs of kidney, heart or brain involvement, but may be considered in patients ?16 years in the absence of clinical signs or symptoms of organ involvement.
  2. Classically affected females and males with non-classical Fabry disease (FD) should be treated as soon as there are early clinical signs of kidney, heart or brain involvement, while treatment may be considered in females with non-classical FD with early clinical signs that are considered to be due to FD.
  3. Treatment should not be withheld from patients with GFR < 45 ml/min/1.73 m2 and from those on dialysis or with cognitive decline, but carefully considered on an individual basis.
  4. Stopping ERT may be considered in patients with end stage FD or other co-morbidities, leading to a life expectancy of <1 year. In those with cognitive decline of any cause, or lack of response for 1 year when the sole indication for ERT is neuropathic pain, stopping ERT may be considered.
  5. Also, in patients with end stage renal disease, without an option for renal transplantation, in combination with advanced heart failure (NYHA class IV), cessation of ERT should be considered.
Comments by Evaluators:
  • Authors are key opinion leaders and leading experts in Fabry disease.
  • Delphi Survey among real experts on Fabry disease.