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.