What is prenatal screening?

To support patients and provide them with a better understanding of Fabry disease, genetic counselling is recommended to be made available for patients and their families by a medical geneticist or a counsellor following diagnosis.1 Genetic counselling also enables patients to understand the genetic inheritance of Fabry disease and identify at-risk family members (see family screening).1,2 In the event that patients want to discuss their reproductive options, it is recommended that genetic counselling is offered pre-conception.1 For example, the possibility of pre-implantation genetic diagnosis to select unaffected embryos or gamete donation should be shared with the patient, in addition to prenatal diagnosis.1,2 In pregnant patients with Fabry disease, prenatal diagnosis can be performed using cultured amniocytes or chorionic villi for molecular testing to determine if the GLA gene variant has been inherited by the foetus.1-3

What is newborn screening?
The first newborn screening programme for Fabry disease was performed in Italy and was published in 2006. On the basis of alpha-galactosidase A (α-Gal A) deficiency and specific GLA variants, the estimated incidence of late-onset Fabry disease was approximately 1 in 3100 males. The incidence of classical Fabry disease was 1 in 37,000 males. The high incidence of late-onset Fabry disease highlighted whether genetic screening for Fabry disease should be performed in the neonatal period,4 as late-onset Fabry disease may be an important, yet latent, health issue.5 For example, one newborn screening study in Taiwan indicated that the frequency of late-onset Fabry disease was ~1 in 1250 males, where the GLA variant IVS4+919G>A was found in 86% of cases.6 Moreover, data from other newborn screening programmes suggest that the incidence or prevalence of Fabry disease is underestimated worldwide (see epidemiology of Fabry disease).6-12 Newborn screening for Fabry disease enables early disease detection prior to symptom onset. Many patients with late-onset Fabry disease may experience a delay in diagnosis; however, early identification of patients using newborn screening programmes enables recognition of the clinical manifestations of the disease, timely treatment initiation and, potentially, prevention of irreversible organ damage.5

One qualitative study sought to determine the opinions and experiences of 38 genetic healthcare providers regarding population-based testing for lysosomal storage disorders, including testing for late-onset disease phenotypes. Of the healthcare providers who were included in the study, newborn screening for Fabry disease was generally considered not appropriate because the clinical manifestations of the disease occur later than the neonatal period. However, it was acknowledged that newborn screening programmes may also lead to diagnosis of affected relatives using family screening, which could be considered a potential benefit. The healthcare providers who participated in this study worked within the field of medical genetics and had experience in treating patients with lysosomal storage disorders, and, in general, felt that any disease included in a newborn screening programme should have an effective treatment and a younger age at onset. In addition, for a disease to be included in a newborn screening programme, the test results of the disease should be straightforward, and the natural history and prognosis of the disease should be well established.13

Nevertheless, a separate study of 91 adults with late-onset lysosomal storage disorders, 47 of whom had Fabry disease, suggested that some patients with the disease (42.6%; 20/47) felt they would have had better life satisfaction had they been diagnosed as a newborn, and their current health would be better (57.5%; 27/47). Of the patients with lysosomal storage disorders included in the study, no patient exhibited symptoms at birth and 46.2% (41/91) were symptom-free until adulthood. More than half of patients (52.8%; 48/91) experienced a diagnostic delay of ≥5 years, 60.9% of whom had Fabry disease (29/47). Some patients (41.1%; 37/91) also indicated that they would have made different life choices, including lifestyle, financial and reproductive decisions had they been diagnosed at birth, assuming treatment was available. The findings from this study suggest that some patients with lysosomal storage disorders are in favour of newborn screening programmes, as they may prevent diagnostic delays and possibly alter life choices.13


C-ANPROM/INT/FAB/0016; Date of preparation: March 2021