Journal article
Allogeneic hematopoietic cell transplantation in Farber disease.
- Ehlert K Department of Pediatric Hematology and Oncology, University Medicine Greifswald, Ferdinand, Sauerbruch-Strasse, D-17475 Greifswald, Germany.
- Levade T Cancer Research Centre of Toulouse, INSERM UMR1037, Toulouse, France.
- Di Rocco M Department Unit of Rare Diseases, Gaslini Institute, Genoa, Italy.
- Lanino E Department Unit of Rare Diseases, Gaslini Institute, Genoa, Italy.
- Albert MH Department of Stem Cell Transplantation, Children's Hospital at Dr von Haunersches Kinderspital, University of München, Munich, Germany.
- Führer M Department of Pediatric Palliative Care, Children's Hospital at Dr von Haunersches Kinderspita, University of München, Munich, Germany.
- Jarisch A Department for Children and Adolescents, Division for Stem Cell Transplantation and Immunology, University Hospital Frankfurt, Frankfurt am Main, Germany.
- Güngör T Department of Stem Cell Transplantation, University Children's Hospital Zürich, Zürich, Switzerland.
- Ayuk F Department of Stem Cell Transplantation, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
- Vormoor J Northern Institute for Cancer Research, Newcastle University, Newcastle upon Tyne, UK.
- 2019-03-01
Published in:
- Journal of inherited metabolic disease. - 2019
Acid Ceramidase
Adolescent
Child
Child, Preschool
DNA Mutational Analysis
Farber Lipogranulomatosis
Female
Hematopoietic Stem Cell Transplantation
Humans
Internationality
Male
Mutation
Survival Rate
Transplantation Conditioning
English
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.
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.
- Language
-
- English
- Open access status
- closed
- Identifiers
-
- DOI 10.1002/jimd.12043
- PMID 30815900
- Persistent URL
- https://sonar.ch/global/documents/30302
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