Introduction
Lysosomal α-galactosidase A deficiency causes Fabry disease (FD)1-3, which was considered to be X-linked recessive and therefore females were simply carriers but more recently, it has been shown to be a variable penetrance dominant trait as up to 70% heterozygous females are symptomatic4,5. The prevalence of Fabry’s disease is 1 in 40000-117,000 but the exact frequency is disputed depending on ascertainment of late-onset cases, female penetrance and variants of unknown significance6,7. Deficiency of lysosomal α-galactosidase A activity causes accumulation of globotriaosylceramide (Gb3), globotriaosylsphingosine (Lyso Gb3) and related glycosphingolipids throughout the body8. Clinical symptoms are variable depending on age of onset and include abdominal pain in 60%, neuropathic pain and sensorineural deafness, multiple angiokeratomas, renal failure, cardiomyopathy and stroke1-3.
Identification of patients with rare diseases is difficult. Case-finding depends on the prior possibility of disease. Populations with end stage renal disease (ESRD) on dialysis show a 10-fold Fabry Disease enrichment compared to the general population7,9 and cases are found in cardiology and stroke clinics7 but unidentified cases may be difficult to locate in the wider population. As enzyme replacement is now available, it would preferable to identify patients prior to onset of renal failure10. The PATHFINDER project is based on the premise of using routine laboratory results to identify patients who should be tested for inherited errors of metabolism. The project design has been validated in patients with other disorders11. This paper describes the use of age and creatinine-based estimated glomerular filtration rate (eGFR) as screening biomarkers for FD.