14800-DvRappard

166 Chapter 10 Extra-neurological involvement Despite the fact that ASA activity has been shown to return to normal reference values after HCT, 5,8 both sulfatide excretion in urine (own unpublished findings) as sulfatide accumulation in visceral organs and in the peripheral nervous systemare not affected by HCT. 4,8,9 In our transplanted patients, we saw remarkably large intrasubject fluctuations of sulfatide excretion in urine after HCT (unpublished data). All values remained above normal references values. We do not understand the reason for this large intrasubject fluctuations. Measurements were corrected for dilution of urine, and a catabolic versus anabolic state would not be expected to be of influence. For the increased sulfatide excretion itself after HCT we hypothesize that damage to kidney tissue, not repaired by the transplantation, or clearance of sulfatides in a tissue dependent pace (possibly slower in the kidney than in the central nervous system), results in this increased excretion. An alternative hypothesis is that the degradation of stored sulfatides requires higher amounts of ASA enzyme than the prevention of storage, 10 implying that HCT does prevent further deterioration but does not restore ASA activity enough to ameliorate stored sulfatides. Another explanation might be that the donor macrophages do not reach the visceral organs (including the gallbladder and kidney) and the peripheral nervous system. The peripheral neuropathy can severely hamper motor function, especially in patients with an earlier onset, after transplantation. 11,12 All in all, the precise mechanism for the ongoing accumulation after HCT is not yet understood but definitely requires further attention since it will help us to optimize treatment options for MLD. It is evident that with the limitations of HCT, other therapy strategies are needed, perhaps even in combination with HCT, certainly for patients with early onset and for those in more advanced stages of the disease. This will be discussed under future perspectives In chapter 9 we reported a high incidence of gallbladder abnormalities found in our MLD patients, suggestive of a causal relationship betweenMLD and the development of gallbladder polyps and eventual carcinoma. 13 The difficulty with gallbladder carcinoma is the extremely fast evolution, implying that usually, once it is symptomatic, curative treatment is no longer possible. Due to the various pathological abnormalities we found in our patients, including hyperplastic polyps, a known precancerous condition, we believe screening of the gallbladder by abdominal ultrasound should be added to the standard clinical care of MLD patients. If the ultrasound shows no abnormalities we recommend a follow-up ultrasound every 2 years. A cholecystectomy is advised for polyps exceeding 5 mm in HCT treated patients and untreated patients in good clinical condition in order to prevent untimely death from a preventable cause and improve quality of life. It is important to bear in mind that, due to the thickness of the gallbladder