Treatment for females is a little bit different than treatment for males. In male patients if the mutation that they have predicts classic Fabry Disease it is typically recommended that they consider starting therapy even without any symptoms at about age 10. If they have any symptoms, even if they are mild, treatment could be commenced at the time - before age 10 - if the family of a male patient requests treatment prior to symptoms. The reason for this is that essentially 100% of the boys will develop progressive disease and if untreated they will eventually go into renal failure, heart failure or have a stroke, and all early - especially if they have had relatives die from that disease and the parents want to prevent that from happening to their child. Early institution of therapy has been shown to be safe, it makes sense to at least be open to that discussion. Females are a little bit different because it can be expected that about 15% will have no disease, and then a significant percentage of women will have later onset disease, with problems only starting in their 40’s or 50’s, and some of them will not have any life-threatening complications. There is currently no optimum time to commence therapy for females with no symptoms.
Females who have symptoms should have the same policy as the boys. If a girl develops pain and she’s only 6 years old, she should be put on therapy. If she develops recurrent diarrhea and she’s only 5 years old, she should be put on therapy. Anybody with symptoms should be put on therapy. On the other hand, if a female patient has no symptoms, typically monitoring is recommended, and pediatricians ought to monitor in the most sensitive ways that are available. This is a little bit problematic currently but looking for any signs of kidney disease, any signs of heart disease in addition to the pain, the fatigue, the gastrointestinal symptoms. If a female with a strong family history of Fabry Disease comes and wants therapy and is asymptomatic what should the pediatrician recommend? One option is to get either a kidney biopsy or some detailed but not readily available assessments for biomarkers before initiating therapy in an asymptomatic female. This is due to the desire to not treat people who aren’t going to develop disease. Presently, the mutation status for females is not adequate to predict who will develop symptoms and who will not whereas the mutation status for the males is generally adequate for predicting who will develop disease and who will not.