Allogeneic hematopoietic cell transplantation in Farber disease
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Farber disease (FD) is a rare, lysosomal storage disorder caused by deficient acid ceramidase activity. FD has long been considered a fatal disorder with death in the first three decades of life resulting either from respiratory insufficiency as a consequence of airway involvement or from progressive neurodegeneration because of nervous system involvement. Peripheral symptoms associated with FD, including inflammatory joint disease, have been described to improve relatively rapidly after hematopoietic cell transplantation (HCT).
To evaluate the disease-specific status and limitations in the long-term follow-up after HCT, investigate genotype/phenotype correlations and the benefit of allogeneic HCT in FD patients with nervous system involvement.
Patients and methods
Transplant- and disease-related information of ten FD patients was obtained by using a questionnaire, physicians’ letters and additional telephone surveys. ASAH1 gene mutations were identified to search for genotype/phenotype correlations.
After mainly busulfan-based preparative regimens, all patients engrafted with one late graft loss. The inflammatory symptoms resolved completely in all patients. Abnormal neurologic findings were present pre-transplant in 4/10 patients, post-transplant in 6/10 patients. Mutational analyses revealed new mutations in the ASAH1 gene and a broad diversity of phenotypes without a genotype/phenotype correlation. With a median follow-up of 10.4 years, overall survival was 80% with two transplant-related deaths.
Allogeneic HCT leads to complete and persistent resolution of the inflammatory aspects in FD patients. It appears to have no beneficial effect on progression of nervous system involvement. New mutations in the acid ceramidase gene were identified. A genotype/phenotype correlation could not be established.
Karoline Ehlert wishes to thank Heribert Juergens and Claudia Rossig as well as Alex Solyom and Ed Schuchman for their valuable contributions.
Compliance with ethical standards
Conflict of interest
K. Ehlert, T. Güngör, M. Führer, F. Ayuk, J. Vormoor, E. Lanino, T. Levade declare that they have no conflict of interest. M. Di Rocco has received financial support by Genzyme Sanofi, Shire, Alexion, Regeneron, Clementia (travel expenses, payment for lectures, board membership). A. Jarisch has received travel grants from Novartis. M. Albert owns stock in Amgen and has received research support from GSK.
All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000 (5). Informed consent was obtained from all patients for being included in the study.
This article is a retrospective analysis without any impact or effect on the patients involved. Allogeneic cell transplantation is currently considered an individual treatment approach for patients with Farber disease. The patients and/or caregivers consented to the procedure in their respective institutions within Europe.
Additional informed consent was obtained from all patients for whom identifying information is included in this article.
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