Prolonged hyperlipasemia attributable to a novel type of macrolipase

Background: We present the case of an 80-year-old woman who was admitted to hospital with an intermittent volvulus of the right colon. A total colecto my was performed. Initially, serum amylase and lipase increased concordantl y, but after a few weeks amylase normalized (85 U/L), whereas lipase increa sed to 3764 U/L. This discrepancy and persistence of hyperlipasemia suggest ed a macromolecular form of lipase. Methods: The nature of the macromolecular complex was studied using high-pr essure liquid gel-permeation chromatography, affinity chromatography, (immu no) electrophoresis, and immunodiffusion. Results: Gel-permeation chromatography revealed a macrolipase, with a molec ular mass >900 kDa, that contributed up to 56% of total serum lipase activi ty. Butanol extraction of the specimen did not alter the elution profile. T he thermostabilities of pancreatic lipase and the macroform were similar, w hereas activation energy (E-a) was lower in the macromolecular lipase (28 /- 4 kJ(.)mol(-1.)K(-1) vs 48 +/- 7 kJ(.)mol(-1.)K(-1) (P = 0.02). Agarose electrophoresis showed a broad band of lipase activity at the application s ite. Protein A-Sepharose affinity gel chromatography excluded IgG-linked li pase. Agarose electrophoresis and immunofixation excluded linkage to other immunoglobulins. Radial immunodiffusion did not show lipase activity in the immunoglobulin precipitation bands. Radial immunodiffusion with alpha (2)- macroglobulin (alpha (2)-MG) antibodies showed a diffuse spot of lipase act ivity within the precipitation band, suggesting a macromolecular associatio n between lipase and alpha (2)-MG. Affinity gel chromatography against alph a (2)-MG showed lipase activity in the alpha (2)-MG-bound fractions. Conclusion: This is the first report of a macrolipase in which an associati on between alpha (2)-MG and lipase is described. (C) 2000 American Associat ion for Clinical Chemistry.