14800-DvRappard

170 Chapter 10 Intravenous ERT has not been efficient in controlling CNS disease manifestations, and therefore intrathecal ERT agent delivery and trials are ongoing to prove its efficacy. One such trial, using a biological recombinant of human ASA, has now completed, but results are pending (clinical trials.gov: NCT01510028). Newborn screening Criteria for inclusion of diseases in screening programs are broadly based on frequency, severity of the disease in the untreated population, availability of reliable testing methodology, effective treatment options and cost effectiveness. 19 Other metabolic diseases such as X-linked adrenoleukodystrophy (X-ALD) and mucopolysaccharidosis type I (MPS-I) have recently been recommended for newborn screening (NBS) in the Netherlands. Krabbe disease, another lysosomal storage disorder affecting the CNS and PNS, has a disease course comparable to MLD. NBS for Krabbe disease has been implemented in the US (in the state of New York) since 2006. 20 Early diagnosed infants can be treated with HCT. The inclusion of MLD in the NBS program is complicated by the fact that HCT is not an effective therapy for all subtypes. HSC-GT is now emerging and results are promising and suggestive of a safe and effective therapy also for the late- infantile subtype. This would make MLD a disease with (possible) effective treatment options for all subtypes, warranting therefore implementation within NBS. Still, it is essential to know what subtype a patient would develop; most of all to determine the best moment for treatment. Subtype determination would require mutation screening after ASA activity has been found low, but is complicated by the heterogeneity of disease causing mutations. However, it is known that if a patient is homozygous for mutations predicted to lead to complete loss of ASA activity, they will develop the late- infantile form of the disease. 21 In general, the more effective ASA is produced, the later the onset of the disease. Regarding the best moment for treatment, the question arises whether the earlier is per definition the better. For late-infantile patients this seems to be the case, but for adult patients one could question whether the benefit of treatment earlier than needed at a young age outweighs the possible risk of treatment related mortality and morbidity, risking otherwise healthy years. The best moment for treatment will therefore always remain a decision of both doctor and patient, different for each individual. More experiencewith the above-mentioned therapies and combinations of thesewill broaden our knowledge and will able physicians to provide the best possible counseling, Better understanding of the disease and its pathomechanisms will in the future optimize treatment options and will hopefully eventually make this devastating disease a treatable disorder, for all patients.