Farber Disease — Disease Description With Case Reports

Чикова, И. А.; Buchinskaya, Natalia V.; Костик, М. М.; Авраменко, В. В.; Krasnogorskaya, Olga L.; Nasirov, R. A.; Levade, Thierry; Часнык, В. Г.

doi:10.15690/vsp.v13i6.1207

Cited by 3 publications

(1 citation statement)

References 18 publications

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“…Most variants leading to the more severe Farber phenotype represent founder mutations in specific populations (geographical or ethnic) or private mutations within a family that are not represented in public genome databases. A patient reported by Chikova et al (2014) was excluded from the analysis, as one of the reported variants likely represents a polymorphism, with a minor allele frequency of 3.7% in the general population and as high as 6.9% in some populations.…”

Section: Mutational Spectrummentioning

confidence: 99%

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy

Elsea

Sólyom²,

Martin

et al. 2020

Human Mutation

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Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy are a spectrum of rare lysosomal storage disorders characterized by acid ceramidase deficiency (ACD), resulting from pathogenic variants in N‐acylsphingosine amidohydrolase 1 (ASAH1). Other than simple listings provided in literature reviews, a curated, comprehensive list of ASAH1 mutations associated with ACD clinical phenotypes has not yet been published. This publication includes mutations in ASAH1 collected through the Observational and Cross‐Sectional Cohort Study of the Natural History and Phenotypic Spectrum of Farber Disease (NHS), http://ClinicalTrials.gov identifier NCT03233841, in combination with an up‐to‐date curated list of published mutations. The NHS is the first to collect retrospective and prospective data on living and deceased patients with ACD presenting as Farber disease, who had or had not undergone hematopoietic stem cell transplantation. Forty‐five patients representing the known clinical spectrum of Farber disease (living patients aged 1–28 years) were enrolled. The curation of known ASAH1 pathogenic variants using a single reference transcript includes 10 previously unpublished from the NHS and 63 that were previously reported. The publication of ASAH1 variants will be greatly beneficial to patients undergoing genetic testing in the future by providing a significantly expanded reference list of disease‐causing variants.

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Section: Mutational Spectrummentioning

confidence: 99%

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy

Elsea

Sólyom²,

Martin

et al. 2020

Human Mutation

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Acid ceramidase deficiency: Farber disease and SMA-PME

Yu¹,

Amintas²,

Levade

et al. 2018

Orphanet J Rare Dis

104

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Acid ceramidase (ACDase) deficiency is a spectrum of disorders that includes a rare lysosomal storage disorder called Farber disease (FD) and a rare epileptic disorder called spinal muscular atrophy with progressive myoclonic epilepsy (SMA-PME). Both disorders are caused by mutations in the ASAH1 gene that encodes the lysosomal hydrolase that breaks down the bioactive lipid ceramide. To date, there have been fewer than 200 reported cases of FD and SMA-PME in the literature. Typical textbook manifestations of classical FD include the formation of subcutaneous nodules, accumulation of joint contractures, and development of a hoarse voice. In reality, however, the clinical presentation is much broader. Patients may develop severe pathologies leading to death in infancy or may develop attenuated forms of the disorder wherein they are often misdiagnosed or not diagnosed until adulthood. A clinical variability also exists for SMA-PME, in which patients develop progressive muscle weakness and seizures. Currently, there is no known cure for FD or for SMA-PME. The main treatment is symptom management. In rare cases, treatment may include surgery or hematopoietic stem cell transplantation. Research using disease models has provided insights into the pathology as well as the role of ACDase in the development of these conditions. Recent studies have highlighted possible biomarkers for an effective diagnosis of ACDase deficiency. Ongoing work is being conducted to evaluate the use of recombinant human ACDase (rhACDase) for the treatment of FD. Finally, gene therapy strategies for the treatment of ACDase deficiency are actively being pursued. This review highlights the broad clinical definition and outlines key studies that have improved our understanding of inherited ACDase deficiency-related conditions.Electronic supplementary materialThe online version of this article (10.1186/s13023-018-0845-z) contains supplementary material, which is available to authorized users.

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Lysosomal storage diseases. Sphingolipidoses — Fabry, Gaucher and Farber diseases

et al. 2022

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Sphingolipidoses are genetically heterogeneous group of rare monogenic metabolic diseasesб caused by inherreted deficiency of enzymes involved in the degradation of sphingolipids. Sphingolipids are catabolized in lysosomes, where glycohydrolases degrade them by separation of terminal sugars to core ceramide. All sphingolipidoses are characterized by abnormal deposition of a large amount of sphingolipids and other unsplit products of lipid metabolism, mainly in parenchymal organs, bone marrow and brain. Among sphingolipidoses, such groups of diseases as glycosphingolipidoses, gangliosidoses and leukodystrophies are distinguished. This review presents the epidemiology, clinical, biochemical and molecular characteristics of the three main types of glycosphingolipidoses Fabry disease, Gaucher disease and Farber disease, caused by the mutations in the genes of -galactosidase A (GLA), glucocerebrosidase (GBA) and acid ceramidase (ASAH1), respectively. Currently, there is an increased interest in glycosphingolipidoses due to the identification of the spectrum and frequencies of mutations in the GLA, GBA and ASAH1 genes in various populations, including Russia, and the practical availability of individual molecular diagnostic methods. A description of the existing experimental models, their role in the study of the biochemical basis of the pathogenesis of these severe hereditary diseases and the development of various therapeutic approaches are given. We discuss, firstly, the possibility of early diagnosis of Fabry disease, Gaucher and Farber based on neonatal screening and examination of high risk groups of patients in order to improve the effectiveness of their prevention and treatment, as well as (secondly) the advantages and disadvantages of the main approaches to the treatment of these serious diseases, such as bone marrow and hematopoietic stem cell transplantation, enzyme replacement therapy, substrate reduction therapy, gene therapy and genome editing.

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Farber Disease — Disease Description With Case Reports

Cited by 3 publications

References 18 publications

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy

ASAH1 pathogenic variants associated with acid ceramidase deficiency: Farber disease and spinal muscular atrophy with progressive myoclonic epilepsy

Acid ceramidase deficiency: Farber disease and SMA-PME

Lysosomal storage diseases. Sphingolipidoses — Fabry, Gaucher and Farber diseases

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