UMLS:C0019214 - FACTA Search

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Query: UMLS:C0019214 (hepatosplenomegaly)
4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 1-week-old baby boy presented with hepatosplenomegaly, coarse facial features, and cloudy corneas. A metabolic storage disease was considered and he underwent cutaneous and liver biopsy. By light microscopy the skin was normal. Kupffer cells were enlarged and had foamy cytoplasm. Ultrastructural examination of skin and liver demonstrated features compatible with Farber's disease: curvilinear and "banana" bodies, zebra-like structures, and concentric lamellar bodies. A deficiency of lysosomal acid ceramidase was subsequently demonstrated in cultured fibroblasts and in liver tissue corroborating the ultrastructural findings.
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PMID:Farber's disease: a fine structural study. 311 21

Farber's lipogranulomatosis is an inborn lipid storage disease characterized by tissue accumulation of ceramide due to deficient activity of lysosomal ceramidase. Symptoms include painful swelling of joints, subcutaneous nodules, a hoarse cry, hepatosplenomegaly and nervous system dysfunction of markedly variable degree. In most cases the neural dysfunction rather than the general dystrophy, seems to limit the duration of Farber disease. We examined whether the severity can be shown as a function of ceramide turnover by lysosomal ceramidase. The lysosomal degradation of sphingomyelin-derived ceramide was studied in situ in patient skin fibroblasts and lymphoid cells loaded with LDL-associated radioactive sphingomyelin. We could show for the first time a significant correlation between the ceramide accumulated in situ and the severity of Farber disease. Our method provides an alternative means for determining ceramide degradation by lysosomal ceramidase, but in intact cells. The relatively simple method is at least of the same diagnostic use for Farber disease as the in vitro assay of acid ceramidase using cell homogenates and may also have some prognostic use.
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PMID:Neurodegenerative course in ceramidase deficiency (Farber disease) correlates with the residual lysosomal ceramide turnover in cultured living patient cells. 874 52

We report a case of Farber lipogranulomatosis in a girl with hepatosplenomegaly, macular cherry-red spot, and subcutaneous nodules who developed liver dysfunction with jaundice and ascites, and myelophthisic anaemia because of infiltration of bone marrow with storage cells. Acid ceramidase assay confirmed the diagnosis. We conclude that the bone marrow dysfunction and cherry-red spot are features of type IV Farber lipogranulomatosis that have not been previously recognized, and should be added to the clinical phenotypic description.
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PMID:Bone marrow involvement and obstructive jaundice in Farber lipogranulomatosis: clinical and autopsy report of a new case. 889 23

Farber disease (FD) is a debilitating lysosomal storage disorder characterized by severe inflammation and neurodegeneration. FD is caused by mutations in the ASAH1 gene, resulting in deficient acid ceramidase (ACDase) activity. Patients with ACDase deficiency exhibit a broad clinical spectrum. In classic cases, patients develop hepatosplenomegaly, nervous system involvement, and childhood mortality. Ocular manifestations include decreased vision, a grayish appearance to the retina with a cherry red spot, and nystagmus. That said, the full effect of ACDase deficiency on the visual system has not been studied in detail. We previously developed a mouse model that is orthologous for a known patient mutation in Asah1 that recapitulates human FD. Herein, we report evidence of a severe ocular pathology in Asah1^P361R/P361R mice. Asah1^P361R/P361R mice exhibit progressive retinal and optic nerve pathology. Through noninvasive ocular imaging and histopathological analyses of these Asah1^P361R/P361R animals, we revealed progressive inflammation, the presence of retinal dysplasia, and significant storage pathology in various cell types in both the retina and optic nerves. Lipidomic analyses of retinal tissues revealed an abnormal accumulation of ceramides and other sphingolipids. Electroretinograms and behavioral tests showed decreased retinal and visual responses. Taken together, these data suggest that ACDase deficiency leads to sphingolipid imbalance, inflammation, dysmorphic retinal and optic nerve pathology, and severe visual impairment.
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PMID:Acid Ceramidase Deficiency in Mice Leads to Severe Ocular Pathology and Visual Impairment. 3047 9

Farber disease (FD) is a rare lysosomal storage disorder (LSD) characterized by systemic ceramide accumulation caused by a deficiency in acid ceramidase (ACDase). In its classic form, FD manifests with painful lipogranulomatous nodules in extremities and joints, respiratory complications, and neurological involvement. Hepatosplenomegaly is commonly reported, and severe cases of FD cite liver failure as a cause of early death. Mice homozygous for an orthologous patient mutation in the ACDase gene (Asah1^P361R/P361R) recapitulate the classical form of human FD. In this study, we demonstrate impaired liver function and elevation of various liver injury markers in Asah1^P361R/P361R mice as early as 5 weeks of age. Histopathology analyses demonstrated significant formation and recruitment of foamy macrophages, invasion of neutrophils, progressive tissue fibrosis, increased cell proliferation and death, and significant storage pathology within various liver cell types. Lipidomic analyses revealed alterations to various lipid concentrations in both serum and liver tissue. A significant accumulation of ceramide and other sphingolipids in both liver and hepatocytes was noted. Sphingolipid acyl chains were also altered, with an increase in long acyl chain sphingolipids coinciding with a decrease in ultra-long acyl chains. Hepatocyte transcriptome analyses revealed significantly altered gene transcription. Molecular pathways related to inflammation were found activated, and molecular pathways involved in lipid metabolism were found deactivated. Altered gene transcription within the sphingolipid pathway itself was also observed. The data presented herein demonstrates that deficiency in ACDase results in liver pathology as well as sphingolipid and gene transcription profile changes that lead to impaired liver function.
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PMID:Hepatic pathology and altered gene transcription in a murine model of acid ceramidase deficiency. 3118 26