Department of Pediatric Hematology and Oncology, University Medicine Greifswald, Ferdinand, Sauerbruch-Strasse, D-17475 Greifswald, Germany.
Cancer Research Centre of Toulouse, INSERM UMR1037, Toulouse, France.
J Inherit Metab Dis. 2019 Mar;42(2):286-294. doi: 10.1002/jimd.12043. Epub 2019 Feb 27.
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.
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.
法伯病（FD）是一种罕见的溶酶体贮积病，由酸性神经酰胺酶活性缺乏引起。FD 长期以来被认为是一种致命疾病，患者在生命的头三十年因呼吸道受累导致呼吸功能不全或因神经系统受累导致进行性神经退行性变而死亡。与 FD 相关的外周症状，包括炎症性关节病，在造血细胞移植（HCT）后相对较快地改善。
评估 HCT 后长期随访中的疾病特异性状况和限制，研究基因型/表型相关性以及神经受累 FD 患者异基因 HCT 的益处。
通过问卷调查、医生信函和额外的电话调查，获得了 10 例 FD 患者的移植和疾病相关信息。确定 ASAH1 基因突变以寻找基因型/表型相关性。
在主要基于白消安的预处理方案后，所有患者均植入一个迟发性移植物丢失。所有患者的炎症症状均完全缓解。10 例患者中有 4 例在移植前存在异常神经表现，10 例患者中有 6 例在移植后存在异常神经表现。突变分析显示 ASAH1 基因的新突变和广泛的表型多样性，没有基因型/表型相关性。中位随访 10.4 年后，总生存率为 80%，有 2 例移植相关死亡。
异基因 HCT 可导致 FD 患者炎症表现完全和持续缓解。它似乎对神经系统受累的进展没有有益影响。鉴定出酸性神经酰胺酶基因的新突变。未建立基因型/表型相关性。
