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)
Krivit
W
W
University of Minnesota.
Freese
D
D
Chan
K W
KW
Kulkarni
R
R
D016026:Bone Marrow Transplantation; D002675:Child, Preschool; D003131:Combined Modality Therapy; D006801:Humans; D007223:Infant; D008049:Lipase / Q000172:deficiency / Q000378:metabolism; D008148:Lovastatin / Q000627:therapeutic use; D015223:Wolman Disease / Q000188:drug therapy / Q000201:enzymology / Q000601:surgery*
D008148:Lovastatin; D008049:Lipase