Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis

Kostik, Mikhail M.; Чикова, И. А.; Авраменко, В. В.; Vasyakina, Laly I.; Trionnaire, Emmanuelle Le; Chasnyk, Vyacheslav; Levade, Thierry

doi:10.1007/s10545-012-9573-z

Cited by 22 publications

(13 citation statements)

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“…In infants, Farber's disease may present as an acute inflammatory condition mimicking JIA . Hand radiographs of a boy described by Kostik et al showed thinning of the diaphysis and osteopenia, and it is likely that skeletal involvement in that boy may have progressed to look like the osteolysis in our patients. Children with the so‐called intermediate or mild forms may lack neurologic involvement but have severe articular and systemic involvement (particularly of the airways) and may have longer survival times.…”

Section: Discussionmentioning

confidence: 61%

“…The c.505T>C (p.Trp169Arg) mutation has been observed in 2 patients with “classic” Farber's disease (Levade T: unpublished observations). The c.760A>G (p.Arg254Gly) mutation has been reported at homozygosity in a young patient presenting in the first year of life with a clinical picture mimicking severe juvenile idiopathic arthritis (JIA) . Genotype–phenotype correlations are not easily recognized in Farber's disease, but the protracted clinical course associated with compound heterozygosity for these mutations is surprising and calls for further studies at the cellular and biochemical level.…”

Section: Discussionmentioning

confidence: 99%

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Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Bonafé

Kariminejad²,

et al. 2016

Arthritis & Rheumatology

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Objective. To establish a diagnosis and provide counseling and treatment for 3 adult patients from one family presenting with peripheral osteolysis.Methods. Following clinical and radiographic assessment, exome sequencing, targeted gene resequencing, and determination of enzyme activity in cultured fibroblasts were performed.Results. The proband (age 40 years) had a history of episodic fever and pain in childhood that subsided around puberty. He and 2 of his older sisters (ages 58 and 60 years, respectively) showed adult-onset progressive shortening of fingers and toes with redundancy of the overlying skin. Radiographs showed severe osteolysis of the distal radius and ulna, carpal bones, metacarpal bones, and phalanges. Sequencing of the known genes for recessively inherited osteolysis, MMP2 and MMP14, failed to show pathogenic mutations. Exome sequencing revealed compound heterozygosity for mutations c.505T>C (p.Trp169Arg) and c.760A>G (p.Arg254Gly) in ASAH1, the gene coding for acid ceramidase. Sanger sequencing confirmed correct segregation in the family, and enzyme activity in fibroblast cultures from the patients was reduced to~8% of that in controls, confirming a diagnosis of Farber's disease.Conclusion. Our findings indicate that hypomorphic mutations in ASAH1 may result in an osteoarticular phenotype with a juvenile phase resembling rheumatoid arthritis that evolves to osteolysis as the final stage in the absence of neurologic signs. This observation delineates a novel type of recessively inherited peripheral osteolysis and illustrates the long-term skeletal manifestations of acid ceramidase deficiency (Farber's disease) in what appear to be the oldest affected individuals known so far.

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Section: Discussionmentioning

confidence: 61%

Section: Discussionmentioning

confidence: 99%

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Bonafé

Kariminejad²,

et al. 2016

Arthritis & Rheumatology

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“…Briefly, patient 01 carries two point mutations. The c.760A > G substitution (p.Arg254Gly) in exon 10 has already been described . The other one, c.1175G > A, p.Cys392Tyr, has not been described so far.…”

Section: Resultsmentioning

confidence: 96%

Allogeneic hematopoietic cell transplantation in Farber disease

Ehlert

Levade

Rocco

et al. 2019

J of Inher Metab Disea

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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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“…It is suggested, however, that the actual number of cases is being underestimated due to misdiagnosis 20 . Due to the heterogeneity of FD presentation, a high percentage of cases with mild symptoms are initially diagnosed as juvenile idiopathic arthritis (JIA) 21, 22 . The accurate diagnosis of FD is of crucial importance, as the development of enzyme replacement therapy was announced in July 2016 (Enzyvant Sciences Ltd).…”

Section: Introductionmentioning

confidence: 99%

C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease

Cozma

Iurașcu

Eichler

et al. 2017

Sci Rep

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Farber disease (FD) is a rare autosomal recessive disease caused by mutations in the acid ceramidase gene (ASAH1). Low ceramidase activity results in the accumulation of fatty substances, mainly ceramides. Hallmark symptoms at clinical level are periarticular nodules, lipogranulomas, swollen and painful joints and a hoarse voice. FD phenotypes are heterogeneous varying from mild to very severe cases, with the patients not surviving past their first year of life. The diagnostic aspects of FD are poorly developed due to the rarity of the disease. In the present study, the screening for ceramides and related molecules was performed in Farber affected patients (n = 10), carriers (n = 11) and control individuals (n = 192). This study has the highest number of enrolled Farber patients and carriers reported to present. Liquid chromatography multiple reaction mass spectrometry (LC/MRM-MS) studies revealed that the ceramide C26:0 and especially its isoform 1 is a highly sensitive and specific biomarker for FD (p < 0.0001). The new biomarker can be determined directly in the dried blood spot extracts with low sample consumption. This allows for easy sample preparation, high reproducibility and use in high throughput screenings.

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Farber lipogranulomatosis with predominant joint involvement mimicking juvenile idiopathic arthritis

Cited by 22 publications

References 1 publication

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Brief Report: Peripheral Osteolysis in Adults Linked to ASAH1 (Acid Ceramidase) Mutations: A New Presentation of Farber's Disease

Allogeneic hematopoietic cell transplantation in Farber disease

C26-Ceramide as highly sensitive biomarker for the diagnosis of Farber Disease

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