Newborn Screening in Fabry Disease

Fabry disease (FD) is an X-linked genetic disease caused by deficient α galactosidase A activity, leading to a lysosomal storage disorder of globotriaosylceramide, causing organ damages. There are two most common clinical manifestations of the disease: classic FD with a typical onset of symptoms in childhood in males, and later-onset variants which may include female heterozygotes. The highly heterogeneous and nonspecific nature of FD's symptoms and limited physicians' awareness result in a significant diagnostic and therapeutic delay. Even though the implementation of newborn screening (NBS) gives us an opportunity for early diagnosis and timely treatment, it has not yet been universally adopted. Over twenty pilot studies and screening programs worldwide have been published, showing that FD is more prevalent than previously estimated, exceeding 1 in 40,000 males, mainly due to the high incidence of variants of unknown significance (VUSs). They also raised controversies regarding the diagnostic methods, results interpretation, ethical issues, clinical approach, and economic burden. This review analyzes recent studies of NBS for FD; examines the screening methods, prevalence findings, and natural history data; and assesses the benefits and risks of NBS. We conclude with suggestions for the screening program design and research priorities to ensure that screening leads to improved health outcomes with acceptable costs and psychosocial impact.