- Email: [email protected]
Macroenzymes: too often overlooked
Journal of Hepatology 38 (2003) 119 www.elsevier.com/locate/jhep
Letter to the Editor
Macroenzymes: too often overlooked To the Editor: Macroenzymes are serum enzymes that form high-molecular-mass complexes by association with immunoglobulins [1], resulting in elevated serum activity. This is a wellknown phenomenon for serum amylase and creatine kinase (CK), whereas aspartate aminotransferase (AST) macroenzymes are less frequent. AST is present in several organs with the highest concentration in the liver, making AST a sensitive indicator of liver damage. MacroAST may occur in asymptomatic patients [2]. However, a recent review on abnormal liver enzyme in asymptomatic patients does not address this possibility [3]. We report a case of isolated, asymptomatic AST increase, which was diagnosed as a macroenzyme only after 2 years of investigations. A 33-year-old woman, with no history of alcohol, medications, illicit drug consumption or exposure to solvents, had an increased AST level (146 units/l, normal range 10–35) during routine blood tests, which was confirmed at monthly controls (average 190–260 units/l). Alanine aminotransferase, bilirubin, CK, hepatitis serology, thyroid function, neoplastic markers, autoantibodies (antinuclear, anti-smooth muscle, anti-liver-kidney-microsomal, anti-transglutaminase), alpha1-antitrypsin, aptoglobin, iron, ferritin, ceruplasmin, serum and urine copper were within the normal range. Liver ultrasonography results were normal. Eventually, laparoscopy and liver biopsy were performed. Macroscopically, the liver was regular, and the histological evaluation was unremarkable. Only 2 years later, the search for AST isoenzymes was suggested. Immunoprecipitation and immunoelectrophoresis [4] of AST isoenzymes revealed that AST was combined with IgGs, carrying k chains, to form a macromolecular antigen-antibody AST-IgG complex. Papain digestion showed the Fab portion of the IgG as the binding site of the immunoglobulin. A 2 year retrospective study on the frequency of macroenzymes in our hospital laboratory gave the following
results: amylase 6.2% (17/272), CK 1.7% (3/175), lactate dehydrogenase 0.46% (2/430), AST 60% (3/5), and lipase 100% (1/1). The high rates of macroAST and macro-lipase likely reflect a selection bias, since the search for these isoenzymes is requested for patients with persistently high enzymatic activity of unknown etiology, as the case reported. In contrast, other isoenzymes provide useful information for diagnosing or monitoring several conditions other than macroenzymes. The prevalence of macroAST in the general population is not known, but also in patients in whom increased AST is incidentally detected, the possibility of macroAST is often overlooked. A macroenzyme analysis should always be included in the evaluation of asymptomatic AST increase to avoid unnecessary, costly, and invasive procedures. Chiara Briani 1, Martina Zaninotto 2, Massimo Forni 2, Patrizia Burra 3 1 Department of Neurological and Psychiatric Sciences, University of Padova, Via Giustiniani, 5, 35128 Padova, Italy, 2Department of Laboratory Medicine, University of Padova, Padova, Italy, 3 Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy
References [1] Galasso PJ, Litin SC, O’Brien JF. The macroenzymes: a clinical review. Mayo Clin Proc 1993;68:349–354. [2] Litin SC, O’Brien JF, Pruett S, Forsman RW, Burritt MF, Bartholomew LG, et al. Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase. Mayo Clin Proc 1987;62:681–687. [3] Pratt DS, Kaplan MM. Primary care: evaluation of abnormal liverenzyme results in asymptomatic patients. N Engl J Med 2000;342:1266–1271. [4] Stasia MJ, Surla A, Renversez JC, Pene F, Morel-Femelez A, Morel F. Aspartate aminotransferase macroenzyme complex in serum identified and characterized. Clin Chem 1994;40:1340–1343.
0168-8278/02/$20.00 q 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S 0168-827 8(02)00333-1
Letter to the Editor
Macroenzymes: too often overlooked To the Editor: Macroenzymes are serum enzymes that form high-molecular-mass complexes by association with immunoglobulins [1], resulting in elevated serum activity. This is a wellknown phenomenon for serum amylase and creatine kinase (CK), whereas aspartate aminotransferase (AST) macroenzymes are less frequent. AST is present in several organs with the highest concentration in the liver, making AST a sensitive indicator of liver damage. MacroAST may occur in asymptomatic patients [2]. However, a recent review on abnormal liver enzyme in asymptomatic patients does not address this possibility [3]. We report a case of isolated, asymptomatic AST increase, which was diagnosed as a macroenzyme only after 2 years of investigations. A 33-year-old woman, with no history of alcohol, medications, illicit drug consumption or exposure to solvents, had an increased AST level (146 units/l, normal range 10–35) during routine blood tests, which was confirmed at monthly controls (average 190–260 units/l). Alanine aminotransferase, bilirubin, CK, hepatitis serology, thyroid function, neoplastic markers, autoantibodies (antinuclear, anti-smooth muscle, anti-liver-kidney-microsomal, anti-transglutaminase), alpha1-antitrypsin, aptoglobin, iron, ferritin, ceruplasmin, serum and urine copper were within the normal range. Liver ultrasonography results were normal. Eventually, laparoscopy and liver biopsy were performed. Macroscopically, the liver was regular, and the histological evaluation was unremarkable. Only 2 years later, the search for AST isoenzymes was suggested. Immunoprecipitation and immunoelectrophoresis [4] of AST isoenzymes revealed that AST was combined with IgGs, carrying k chains, to form a macromolecular antigen-antibody AST-IgG complex. Papain digestion showed the Fab portion of the IgG as the binding site of the immunoglobulin. A 2 year retrospective study on the frequency of macroenzymes in our hospital laboratory gave the following
results: amylase 6.2% (17/272), CK 1.7% (3/175), lactate dehydrogenase 0.46% (2/430), AST 60% (3/5), and lipase 100% (1/1). The high rates of macroAST and macro-lipase likely reflect a selection bias, since the search for these isoenzymes is requested for patients with persistently high enzymatic activity of unknown etiology, as the case reported. In contrast, other isoenzymes provide useful information for diagnosing or monitoring several conditions other than macroenzymes. The prevalence of macroAST in the general population is not known, but also in patients in whom increased AST is incidentally detected, the possibility of macroAST is often overlooked. A macroenzyme analysis should always be included in the evaluation of asymptomatic AST increase to avoid unnecessary, costly, and invasive procedures. Chiara Briani 1, Martina Zaninotto 2, Massimo Forni 2, Patrizia Burra 3 1 Department of Neurological and Psychiatric Sciences, University of Padova, Via Giustiniani, 5, 35128 Padova, Italy, 2Department of Laboratory Medicine, University of Padova, Padova, Italy, 3 Department of Surgical and Gastroenterological Sciences, University of Padova, Padova, Italy
References [1] Galasso PJ, Litin SC, O’Brien JF. The macroenzymes: a clinical review. Mayo Clin Proc 1993;68:349–354. [2] Litin SC, O’Brien JF, Pruett S, Forsman RW, Burritt MF, Bartholomew LG, et al. Macroenzyme as a cause of unexplained elevation of aspartate aminotransferase. Mayo Clin Proc 1987;62:681–687. [3] Pratt DS, Kaplan MM. Primary care: evaluation of abnormal liverenzyme results in asymptomatic patients. N Engl J Med 2000;342:1266–1271. [4] Stasia MJ, Surla A, Renversez JC, Pene F, Morel-Femelez A, Morel F. Aspartate aminotransferase macroenzyme complex in serum identified and characterized. Clin Chem 1994;40:1340–1343.
0168-8278/02/$20.00 q 2002 European Association for the Study of the Liver. Published by Elsevier Science B.V. All rights reserved. PII: S 0168-827 8(02)00333-1