Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wolman's disease is a fatal disorder characterized by absence of acid lipase and accumulation of cholesterol esters. Inanition due to malabsorption and intractable diarrhea has been the most prominent cause of early demise within the first year. Further complications have included cirrhosis and pulmonary failure due to cholesterol ester storage in respective cells. Although sustained caloric balance can be maintained by total parenteral nutrition, this has not altered the eventual course of disease. The acid lipase deficiency in leucocytes in Wolman's disease can be corrected subsequent to bone marrow transplantation. This has proven to be the case in two patients so transplanted. In two other patients, engraftment was not obtained following bone marrow transplantation. The concept of treatment of Wolman's disease by providing normalization of the acid lipase activity by allogeneic bone marrow transplantation remains valid. However, improvement of bone marrow transplant procedure needs to be implemented since pre-existing morbid pathology enhances toxicity and may prevent engraftment. Alternative modifications for accomplishing sustained engraftment without toxicity need to be examined. Other potential therapies need to be inspected in treatment of patients with Wolman's disease. The capability of reducing cellular cholesterol synthesis by use of lovastatin, an inhibitor of 3-hydroxy-3-methylglutaryl-CoA reductase, is now available. In the future, isolation and purification of acid lipase will allow for direct infusion of missing enzyme. The molecular biology now known concerning acid lipase gene holds promise for the future for recombinant manufacturing of acid lipase. And, gene therapy with its use of autologous bone marrow transplantation will be tried in future.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Wolman's disease: a review of treatment with bone marrow transplantation and considerations for the future. 152 Oct 99

The lipid composition of nerves, with and without xanthomatous alteration, and other tissues, was investigated post-mortem in a 36-year-old man with cholestatic hepatitis of unknown cause and insulin-dependent diabetes mellitus (IDDM). Cholesteryl esters were found to be markedly increased in both endoneurium and epi- and perineurium of hepatic nerves (showing xanthomatous change), but not in sciatic nerve (without this change). Cholesteryl ester concentrations were also increased, but to a lesser degree, in kidney tissue. The fatty acid composition of stored cholesteryl esters in hepatic nerve endoneurium revealed that oleic acid was the most favoured substrate for esterification. A widespread depletion of triacylglycerol was also demonstrated in hepatic and sciatic nerves and liver and skin tissues obtained from this patient. This abnormality did not appear to be due to an alcoholic or biliary cirrhosis, or to inanition. Whether the depletion of triacylglycerol is drug-related or represents an endogenous metabolic error remains unclear.
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PMID:Lipid abnormalities of xanthomatous nerves. 672 18