Farber Disease is an autosomal-recessively inherited, lysosomal storage disorder caused by
acid ceramidase deficiency and associated with distinct clinical phenotypes. Children with significant neurological involvement usually die early in infancy, whereas patients without or only mild neurological findings suffer from progressive joint deformation and
contractures, subcutaneous nodules, inflammatory, periarticular
granulomas, a hoarse voice and finally
respiratory insufficiency caused by
granuloma formation in the respiratory tract and
interstitial pneumonitis leading to death in the third or fourth decade of live. As the inflammatory component of this disorder is caused by some kind of leukocyte dysregulation, allogeneic
hematopoietic stem cell transplantation can restore a healthy immune system and thus may provide a curative option in
Farber Disease patients without neurological involvement. Previous
stem cell transplantations in two children with severe neurological involvement had resulted in a disappointing outcome, as both patients died of progressive deterioration of their neurological status. As a consequence,
stem cell transplantation does not appear to be able to abolish or even reduce the neurotoxic effects of the abundant
ceramide storage in the brain.
METHODS: After myeloablative,
busulfan-based preparative regimens, four
Farber Disease patients without neurological involvement received an allogeneic
hematopoietic stem cell transplantation from related and unrelated donors. Stem cell source was BM in three patients and PBSC in one patient; GvHD-prophylaxis consisted of CsA and short course MTX.
RESULTS AND DISCUSSION: In all patients, HSCT resulted in almost complete resolution of
granulomas and joint
contractures, considerable improvement of mobility and joint motility without relevant
therapy-related morbidities. All patients are alive and well at this point with stabile donor cell chimerism and without evidence of chronic GvHD or other late sequelae of
stem cell transplantation.
CONCLUSION: