Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002986 (Fabry)
 5,646 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 39-year-old male with classical Anderson-Fabry disease (AFD) and long-standing idiopathic splenomegaly, who had been on haemodialysis since the age of 24, was splenectomised for symptomatic pancytopaenia. Spleen enlargement was first noted at clinical presentation, at age 16, but despite thorough investigation its cause remained unclear. Anaemia, leukopaenia and thrombocytopaenia were first observed a few years thereafter, but well before the start of dialytic treatment. On gross pathological examination the spleen weighed 700 g and had a fibrocongestive appearance. Histologically, it showed expansion of the red pulp and decreased white pulp. Some histiocytes and many of the endothelial cells lining the sinusoids had vacuolated cytoplasm with argyrophilic material within, suggesting their involvement in the storage pathology of AFD. In a retrospective review of our cohort of patients with classical AFD (n = 10), complete blood counts showing anaemia, leukopaenia or thrombocytopaenia were found in five, two and four patients, respectively, including a 6-year-old boy, whose spleen was also enlarged. Data from AFD international registries show that peripheral blood cytopaenias, particularly anaemia, are prevalent among these patients. Sinusoidal endothelial involvement resulting in compromise of splenic blood flow may be the cause of congestive splenomegaly and hypersplenism in classical AFD.
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PMID:Splenomegaly, hypersplenism and peripheral blood cytopaenias in patients with classical Anderson-Fabry disease. 1876 74

In adults, elevated transaminases and hepatomegaly, often mild, with moderate to massive idiopathic splenomegaly might hint to a lysosomal storage disease (LSD). In most of these cases, hepatosplenomegaly does not eventually lead to cirrhosis, hepatocellular carcinoma or cholestasis. Nevertheless, the hepatic clinical findings might be the incentive for the patient to present at the physician's office. Many of the currently known >50 lysosomal storage diseases might manifest in liver: out of these, the most important ones in adults are: Gaucher disease, cholesterol ester storage disease (CESD) and the Niemann-Pick diseases. An increase of plasma chitotriosidase should alert the physician for the presence of an LSD. For Gaucher's disease, enzyme supplementation and substrate deprivation constitute effective therapeutic options. Fabry's disease, the most prevalent lysosomal storage disease, does usually not affect the liver, but causes painful episodes of hands' or feet pain (acroparesthesias), left ventricular hypertrophy, renal failure, early stroke and decreased life expectancy. The emerging advent of effective therapeutic options and the cumulative prevalence of lysosomal storage diseases urge the hepatologist to add these diagnostic pathways to the clinical repertoire.
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PMID:Lysosomal storage diseases as differential diagnosis of hepatosplenomegaly. 2095 64

In 1882, Philippe Gaucher described a 32-year-old woman with massive splenomegaly and unusually large cells in the spleen, which he called a "primary epithelioma of the spleen." The systemic nature and inheritance of the disease and its variants involving the viscera and CNS were described over the next century. The delineation of the causal enzymatic defects, genetics, molecular pathology, and genomics have provided pathogenic insights into the phenotypic spectrum and the bases for development of specific therapies for what is now known as Gaucher disease. As a prototype, the clinically and economically successful intracellular enzyme therapy provided the impetus for the expansion of similar research and therapeutic developments for other lysosomal storage diseases (LSDs) and orphan diseases, including Fabry, Pompe, and Niemann-Pick diseases, as well as several mucopolysaccharidoses. Continuing studies of such LSDs, which occur as a group in more than 7000 live births, have revealed the complex molecular interdigitation with the autophagy and apoptotic pathways and proteostasis and the impact of disruptions of the lysosomal/autophagy and proteostasis systems on more common diseases has been recognized. Examples include age-related neurodegenerative diseases (eg, Parkinson disease and Gaucher disease), idiopathic hypertrophic myocardiopathies, stroke and renal failure (eg, Fabry disease), and Nonalcoholic Fatty Liver Disease/Nonalcoholic SteatoHepatitis (NAFLD/NASH) and atherosclerosis (eg, lysosomal acid lipase deficiencies). Although perceived as rare, the availability of treatment and the impact of the LSDs on more common diseases require their integration into routine clinical practice.
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PMID:Gaucher disease and other storage disorders. 2323 55