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Allogeneic hematopoietic cell transplantation in Farber disease


Ehlert, Karoline; Levade, Thierry; Di Rocco, Maja; Lanino, Edoardo; Albert, Michael H; Führer, Monika; Jarisch, Andrea; Güngör, Tayfun; Ayuk, Francis; Vormoor, Josef (2018). Allogeneic hematopoietic cell transplantation in Farber disease. Journal of Inherited Metabolic Disease:Epub ahead of print.

Abstract

BACKGROUND
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).

AIMS
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.

RESULTS
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.

CONCLUSION
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.

Abstract

BACKGROUND
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).

AIMS
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.

RESULTS
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.

CONCLUSION
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.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Scopus Subject Areas:Life Sciences > Genetics
Health Sciences > Genetics (clinical)
Language:English
Date:29 March 2018
Deposited On:30 Jan 2019 10:22
Last Modified:29 Jul 2020 09:28
Publisher:Springer
ISSN:0141-8955
OA Status:Closed
Publisher DOI:https://doi.org/10.1007/s10545-018-0171-6
PubMed ID:29600496

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