Case-finding in Fabry disease: experience from the North of England

The advent of effective therapy for Fabry disease (FD) creates two challenges: (1) how do we identify individuals with the condition early in its natural history, and (2) how many people have the condition and require expensive therapy? Between 1981 and 2011, 17 new FD families were referred to the Northern Genetics Service in the North of England, the majority between 2005 and 2001. Since 2009 we have employed biochemical screening in dried blood spots from individuals with high risk phenotypes, such as left ventricular hypertrophy and unexplained renal failure, to identify four of the new index cases; and we have offered comprehensive cascade genetic testing to identify pre-symptomatic and symptomatic cases of FD in their 233 'at risk' relatives. Overall, this combined approach identified a further 23 symptomatic cases of FD and 38 asymptomatic cases. The uptake of cascade genetic testing in this cohort was 48%, which is similar to other inherited disorders for which there is an effective intervention. The minimum prevalence of GLA mutation in the North of England population at the end of 2011 was 1 in 40,800 and the prevalence of symptomatic FD was 1 in 64,600. Improved uptake of cascade genetic testing would increase these estimates to a maximum of 1 in 21,800 and 1 in 49,000 respectively. We suggest that any protocol for case identification should consist of targeted biochemical screening and coordinated cascade genetic testing.