1/14. Lysosomal acid lipase mutations that determine phenotype in Wolman and cholesterol ester storage disease.Mechanisms producing the divergent phenotypes, wolman disease (WD) and cholesterol ester storage disease (CESD), associated with the genetic deficiency of human lysosomal acid lipase/cholesterol ester hydrolase (hLAL) function were investigated with the determination of HLAL activity levels, mRNA and protein expression, and defects in structural gene sequences in cells from three WD and five CESD patients. Measured with natural substrates, HLAL activities were all below 2% of normal, regardless of phenotype. immunoblotting showed a lack of detectable hLAL protein in all mutant fibroblasts. Four CESD, but no WD genomes contained at least one allele with a specific exon 8 splice junction mutation, c.894 G>A, that encodes a shortened form of hLAL mRNA. Other CESD mutations were identical in type to the WD defects: nucleotide deletions (positions 397, 684, 980), insertions (594), or substitutions (193, 347) that result in premature terminations precluding any function. The only exception was a substitution at nucleotide 866 in the CESD case without an exon 8 splicing mutation; expression of the predicted S289C change in a transfection assay produced a low, but clearly measurable, level of acid esterase activity. Although it is not easily demonstrated in conventional assays, CESD is distinct from WD in that at least one mutant allele has the potential to produce enough residual enzymatic function to ameliorate the phenotype; in the majority of CESD cases this may come from a single, easily detected, splicing mutation in one allele.- - - - - - - - - - ranking = 1keywords = storage disease, storage (Clic here for more details about this article) |
2/14. wolman disease successfully treated by bone marrow transplantation.wolman disease is characterized by severe diarrhea and malnutrition leading to death during infancy. Lysosomal acid lipase deficiency is the cause of the symptoms and signs. It is inherited in an autosomal recessive manner. All Wolman disease patients have adrenal gland calcification. Previous therapeutic attempts have failed to provide remission. We report successful long-term bone marrow engraftment in a patient with wolman disease resulting in continued normalization of peripheral leukocyte lysosomal acid lipase enzyme activity. diarrhea is no longer present. Now, at 4 years of age, this patient is gaining developmental milestones. Cholesterol and triglyceride levels are normal. liver function is normal. This is the first long-term continued remission reported for wolman disease.- - - - - - - - - - ranking = 0.00012206794298729keywords = enzyme (Clic here for more details about this article) |
3/14. Wolman's disease--a case report.Wolman's disease is a rare autosomal recessive lysosomal storage disorder. We report a case, which we identified with foamy histiocytes in bone marrow and adrenal calcification in radiological imaging. The diagnosis can be made on minimal investigation when clinically suspected. But cytogenetic study is required to substantiate the diagnosis further.- - - - - - - - - - ranking = 0.075344896010533keywords = lysosomal storage, storage (Clic here for more details about this article) |
4/14. Isolated fetal ascites caused by wolman disease.wolman disease is a rare autosomal-recessive disorder caused by reduced levels of lysosomal acid lipase. It occurs in infancy and is fatal in most cases before the age of 1 year. Affected infants show signs of lipid storage in most tissues, including hepatosplenomegaly, abdominal distension, vomiting, steatorrhea, failure to thrive, and adrenal calcifications. We present a case of isolated fetal ascites diagnosed at 32 weeks of gestation, with negative work-up for immune and non-immune hydrops fetalis and congenital infections and malformations. After delivery, the diagnosis of wolman disease was established. Although rare, storage diseases such as wolman disease should be considered in cases of isolated fetal ascites.- - - - - - - - - - ranking = 0.21423272474091keywords = storage disease, storage (Clic here for more details about this article) |
5/14. Wolman's disease: ultrasonographic and computed tomographic findings.Acid lipase deficiency which is an inborn error of lipid metabolism leads to an abnormal accumulation of cholesteryl esters and triglycerides in many tissues. It is manifested in two clinical forms: Wolman's disease (WD) which is fatal in infancy and cholesteryl ester storage disease (CESD) which is a milder form and usually presented in adulthood. An infant with a clinical diagnosis of WD was examined with CT and ultrasound. Where as CT showed an enlarged liver with decreased density and heavily calcified adrenal glands, ultrasound revealed an enlarged liver with normal echogenicity, adrenal calcification and thickening of bowel loops. Bowel wall thickening in WD was not demonstrated in the literature before with any imaging modality.- - - - - - - - - - ranking = 0.2keywords = storage disease, storage (Clic here for more details about this article) |
6/14. wolman disease and cholesteryl ester storage disease diagnosed by histological and ultrastructural examination of intestinal and liver biopsy.Deficient activity of lysosomal acid lipase (LAL) results in massive accumulation of cholesteryl esters and triglycerides in most tissues of the body. The deficiency state is expressed in two major phenotypes: wolman disease (WD) and cholesteryl ester storage disease (CESD). WD occurs in infancy and is nearly always fatal before the age of 1 year, whereas CESD can be more benign and may not be detected until adulthood. Since there are no specific routine laboratory observations that suggest these metabolic diseases, diagnosis is based on the clinical picture combined with LAL deficiency in cultured skin fibroblasts or peripheral lymphocytes. Both disorders are rather rare, considering that about a hundred of cases have been described up to now. This study describes the histological and ultrastructural aspects disclosed by intestinal or liver biopsy in three cases of WD and in two cases of CESD. Furthermore, it emphasizes the role of morphological findings in pointing the diagnosis towards a metabolic storage disease.- - - - - - - - - - ranking = 1.2keywords = storage disease, storage (Clic here for more details about this article) |
7/14. Wolman's disease: a review of treatment with bone marrow transplantation and considerations for the future.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)- - - - - - - - - - ranking = 0.014354792683898keywords = storage, enzyme (Clic here for more details about this article) |
8/14. Severe chronic diarrhea and weight loss in cholesteryl ester storage disease: a case report.AIM: An inherited deficiency of human lysosomal acid lipase (LAL) results in the rare conditions of wolman disease and cholesteryl ester storage disease (CESD). We want to present the rare case of CESD in an adult. methods: We report about an adult female patient with severe chronic diarrhea and weight loss as a consequence of CESD. Clinical examination revealed signs of malabsorption and slightly elevated liver enzymes. RESULTS: Histopathologic changes in the liver tissue and dna sequence analysis confirmed the diagnosis of CESD due to homozygosity for the most common CESD mutation, a G934A splice site defect encoded by exon 8 of the lysosomal acid lipase (LIPA) gene. CONCLUSION: It is the first case in the literature with diarrhea as a putative symptom of CESD in adult patients.- - - - - - - - - - ranking = 1.000122067943keywords = storage disease, storage, enzyme (Clic here for more details about this article) |
9/14. wolman disease: diagnosis by leucocyte acid lipase estimation.wolman disease is a rare fatal autosomal recessive disorder caused by absence of acid lipase enzyme leading to accumulation of cholesterol ester. Hepatosplenomegaly is a constant feature and occurs as early as fourth day of life. Progressive mental deterioration may occur after few weeks of onset of symptoms. Adrenal calcification seen on X-ray abdomen, USG or CT scan is the hallmark of wolman disease. For the first time in Indian literature, the authors report a case of wolman disease that was confirmed by acid lipase enzyme estimation.- - - - - - - - - - ranking = 0.00024413588597459keywords = enzyme (Clic here for more details about this article) |
10/14. prenatal diagnosis of heterozygosis in a pregnancy at risk for Wolman's disease at the 8th week of gestation.Wolman's disease is a rare autosomal recessive disease due to lysosomal acid lipase complete deficiency (McKusick 27.800). prenatal diagnosis is based on safe chorionic villus sampling procedures. We test acid lipase activity in cultured chorionic villus cells, selected from a biopsy performed during the 8th week of pregnancy. We now report the first prenatal diagnosis of heterozygosity for Wolman's disease during the first trimester of pregnancy. Reduced acid lipase activity was shown in the chorionic villi cells using a natural substrate (Cholesterol 14C oleate). The diagnosis was confirmed by the demonstration of reduced acid lipase activity in cultured amniotic cells and in the newborn lymphocytes. Early prenatal diagnosis in pregnancies at risk for lysosomal storage diseases is possible when enzyme activity levels in chorionic villi are similar to those in cultured amniotic cells and in infant cells.- - - - - - - - - - ranking = 0.26123423921261keywords = storage disease, lysosomal storage, storage, enzyme (Clic here for more details about this article) |
| | Next -> |