scholarly journals Wolman disease

2021 ◽  
Author(s):  
Francis Fortin
Keyword(s):  
Wolman Disease

scholarly journals Enzyme replacement therapy and hematopoietic stem cell transplant: a new paradigm of treatment in Wolman disease

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Jane E. Potter ◽  
Gemma Petts ◽  
Arunabha Ghosh ◽  
Fiona J. White ◽  
Jane L. Kinsella ◽  
...  
Keyword(s):  
Stem Cell ◽  
Multimodal Therapy ◽  
Hematopoietic Stem Cell Transplant ◽  
Stem Cell Transplant ◽  
Venous Access ◽  
Cell Transplant ◽  
New Paradigm ◽  
Hematopoietic Stem ◽  
Wolman Disease ◽  
Enzyme Replacement

Abstract Background Wolman disease is a rare, lysosomal storage disorder in which biallelic variants in the LIPA gene result in reduced or complete lack of lysosomal acid lipase. The accumulation of the substrates; cholesterol esters and triglycerides, significantly impacts cellular function. Untreated patients die within the first 12 months of life. Clinically, patients present severely malnourished, with diarrhoea and hepatosplenomegaly, many have an inflammatory phenotype, including with hemophagocytic lymphohistiocytosis (HLH). Hematopoietic stem cell transplant (HCT) had been historically the only treatment available but has a high procedure-related mortality because of disease progression and disease-associated morbidities. More recently, enzyme replacement therapy (ERT) with dietary substrate reduction (DSR) has significantly improved patient survival. However, ERT is life long, expensive and its utility is limited by anti-drug antibodies (ADA) and the need for central venous access. Results We describe five Wolman disease patients diagnosed in infancy that were treated at Royal Manchester Children's Hospital receiving ERT with DSR then HCT—multimodal therapy. In 3/5 an initial response to ERT was attenuated by ADA with associated clinical and laboratory features of deterioration. 1/5 developed anaphylaxis to ERT and the other patient died post HCT with ongoing HLH. All patients received allogeneic HCT. 4/5 patients are alive, and both disease phenotype and laboratory parameters are improved compared to when they were on ERT alone. The gastrointestinal symptoms are particularly improved after HCT, with reduced diarrhoea and vomiting. This allows gradual structured normalisation of diet with improved tolerance of dietary fat. Histologically there are reduced cholesterol clefts, fewer foamy macrophages and an improved villous structure. Disease biomarkers also show improvement with ERT, immunotherapy and HCT. Three patients have mixed chimerism after HCT, indicating a likely engraftment-defect in this condition. Conclusion We describe combined ERT, DSR and HCT, multimodal treatment for Wolman disease. ERT and DSR stabilises the sick infant and reduces the formerly described prohibitively high, transplant-associated mortality in this condition. HCT abrogates the problems of ERT, namely attenuating ADA, the need for continuing venous access, and continuing high cost drug treatment. HCT also brings improved efficacy, particularly evident in improved gastrointestinal function and histology. Multimodal therapy should be considered a new paradigm of treatment for Wolman disease patients where there is an attenuated response to ERT, and for all patients where there is a well-matched transplant donor, in order to improve long term gut function, tolerance of a normal diet and quality of life.

A Chinese case of Wolman disease

1989 ◽  
Vol 12 (3) ◽  
pp. 328-328 ◽  
Author(s):  
T. -R. Wang ◽  
S. -M. Chuang
Keyword(s):  
Wolman Disease ◽  
Chinese Case

scholarly journals Characterization of lysosomal acid lipase mutations in the signal peptide and mature polypeptide region causing Wolman disease

2001 ◽  
Vol 42 (7) ◽  
pp. 1033-1040 ◽  
Author(s):  
Oliver Zschenker ◽  
Nikola Jung ◽  
Julia Rethmeier ◽  
Sabine Trautwein ◽  
Stefanie Hertel ◽  
...  
Keyword(s):  
Signal Peptide ◽  
Acid Lipase ◽  
Wolman Disease ◽  
Lysosomal Acid ◽  
Lysosomal Acid Lipase ◽  
Mature Polypeptide

Wolman disease: Diagnosis by leucocyte acid lipase estimation

2005 ◽  
Vol 72 (4) ◽  
pp. 353-354 ◽  
Author(s):  
Talib Y. Surve ◽  
Mamta N. Muranjan ◽  
B. A. Barucha
Keyword(s):  
Disease Diagnosis ◽  
Acid Lipase ◽  
Wolman Disease

Use of New Fluorescent Triacylglycerols for Determining Lipase Activities and Diagnosing Wolman Disease

1988 ◽  
pp. 517-522
Author(s):  
Nicole Dousset ◽  
Anne Nègre ◽  
Valerie Réaud ◽  
Quoc Quan Dang ◽  
Pierre Rogalle ◽  
...  
Keyword(s):  
Wolman Disease

Proposed Treatment for Infants With Wolman Disease

PEDIATRICS ◽  
1989 ◽  
Vol 83 (6) ◽  
pp. 1074-1075
Author(s):  
MOSHE WOLMAN
Keyword(s):  
Lysosomal Enzyme ◽  
Cholesterol Ester ◽  
Reticuloendothelial System ◽  
Cholesterol Esters ◽  
Enzyme Molecule ◽  
Acid Lipase ◽  
Wolman Disease ◽  
Cholesterol Ester Hydrolase ◽  
Ester Hydrolase ◽  
Available Information

Presently available information indicates that Wolman disease is due to a defect in a single lysosomal enzyme molecule, called acid lipase, esterase, or cholesterol ester hydrolase (EC3.1.1.13). Cells of the reticuloendothelial system, hepatocytes, adrenocortical, and presumably many other cells normally, contain a neutral esterase associated with their microsomes, which is not deficient in Wolman disease. Theoretically, catabolism of intracellular hydrophobic cholesterol (esters and triglycerides) should proceed normally in Wolman disease cells whenever the metabolic chain does not depend on lysosomal hydrolysis.

Wolman Disease

2009 ◽  
pp. 2253-2253
Author(s):  
Markus Böhm ◽  
Thomas A. Luger ◽  
Cem Evereklioglu ◽  
Mark Berneburg ◽  
Thomas Schwarz ◽  
...  
Keyword(s):  
Wolman Disease
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