14800-DvRappard

42 Chapter 2 Warfarin administration Vitamin K has been shown to play a role in the modulation of sphingolipid synthesis. 18 It is thought to control the rate-limiting step in the production of sphingolipids and the conversion of cerebrosides to sulfatides. 18 Warfarin as a vitamin K antagonist is hypothesized to reduce the formation of sulfatides. This is currently being tested in a clinical trial for which children with MLD, aged 1-10 years, were included who had received and failed a HSCT or were excluded from the treatment (http://clinicaltrials. gov/ct2/show/NCT00683189). Symptomatic treatment In patients not eligible for HSCT, treatment should be focused on creating the greatest possible comfort for both patients and parents. Feeding via gastrostomy usually relieves discomfort and struggling and prevents aspiration pneumonia. Painful spasms are common and need to be treated with injection of botulinume toxine or (intrathecal) baclofen. Communication, even when speech is lost, can be assisted through electronically devices. Genetic counseling and psychological support are important for the whole family. CONCLUSION Metachromatic leukodystrophy is a devastating disease for which at present no curative treatment is available for many patients. Despite the use of HSCT for leukodystrophies for decades now, the effectiveness of this treatment is still under debate. In general, HSCT does not seem to be beneficial for patients with overt neurological symptoms or the aggressive late infantile form of MLD. Inconsistent results have been reported for asymptomatic patients. A systematic evaluation of the effectiveness of HSCT is needed in order to be able to decide for which patients HSCT is beneficial. Standardized treatment protocols and longer follow-up will help to come to a conclusion. Innovative strategies such as gene therapy and enzyme replacement therapy are now being tested in clinical trials. Gene therapy has the potential to produce more effective levels of enzyme by generating autologous hematopoietic cells that overexpress the ARSA gene, than through HSCT. The preliminary results of the first clinical trial regarding this type of therapy are promising. However, further evaluation regarding the safety and long-term effects of this approach are needed. If the current ongoing clinical trials studying enzyme replacement therapy are able to overcome its main limitation and