286 sions. None was undergoing treatment with hepatotoxic drugs or with drugs that could affect liver enzyme activities. Aminotransferase levels were normal in all family members. Physical examina- tion gave normal results in all except pa- tients 6 and 7. In particular, none had jaundice or hepatosplenomegaly, and none was obese or reported muscle weakness. Neuromuscular status was normal in all. Ultrasound examination of the liver was performed in all. Serum aminotransferase, alkaline phosphatase, gamma glutamyltrans- ferase, cholinesterase, creatine kinase and its isoenzymes, lactate dehydroge- nase and its isoenzymes, aldolase, amy- lase, total bilirubin, conjugated bilirubin, and prothrombin time were evaluated. Hemolytic disorders as a cause of the raised serum AST were explored by means of blood cell count including retic- ulocytes, Coombs’ test, and haptoglobin. Blood urea and creatinine levels were also evaluated. All the enzymes were de- termined at 37° C according to Scandi- navian Society for Clinical Chemistry and Clinical Physiology guidelines. 11 In all patients values were within normal reference range except for aspartate (but not alanine) aminotransferase. All pa- tients underwent tests for viral (hepatitis A, B, and C viruses, cytomegalovirus, and Epstein-Barr virus), metabolic (α-1- antitrypsin, ceruloplasmin, urinary cop- Cryptogenic elevation of aminotrans- ferase values leads to time-consuming clinical, laboratory, and instrumental di- agnostic procedures. In cases in which hepatic and muscle diseases were ex- cluded and aspartate aminotransferase alone was elevated, reduced clearance of high molecular mass complexes was often found to underlie the biochemical abnormality. 1-8 MacroAST, a benign condition, 6 has been described in only 2 children 7,9 and in 2 adolescents. 8,10 The aspects to be clarified in children are whether a cutoff level of AST activity may suggest a diagnosis of macroAST, whether the macroAST phenomenon is M Macroenzyme investigation and monitoring in children with persistent increase of aspartate aminotransferase of unexplained origin Giuliana Fortunato, MD, Raffaele Iorio, MD, Pietro Esposito, PhD, Maria Marinella Lofrano, PhD, Angela Vegnente, MD, and Pietro Vajro, MD persistent, and whether macroAST is disease-associated. In an attempt to ad- dress these issues, we investigated and monitored macroAST in 10 children with persistent isolated increased levels of serum AST. METHODS Patients Ten children (6 girls; mean age 6.1 ± 3 years; range 1.5 to 10 years) with persis- tent (>6 months) cryptogenic increased serum levels of AST and normal values of other liver and muscle enzymes were observed from 1989 to 1996. Patient 1 was previously described as a case re- port. 7 Elevated aminotransferase values were discovered during laboratory screening within the framework of a rou- tine physical examination in 8 patients. Laboratory screening was prompted by plagiocephaly in patient 6 and by failure to thrive in patient 7. In 5 patients (pa- tients 2, 4, 7, 9, and 10) previous labora- tory screening (4.1 ± 3 years earlier) showed normal AST values. None of the 10 children had ever been affected by major medical problems. None had re- ceived blood or blood product transfu- From the Department of Biochemistry and Medical Biotechnology, and the Department of Pediatrics, Medical School of the University of Naples “Federico II”, Napoli, Italy. Supported in part by MURST and Regione Cam- pania. Submitted for publication Aug 14, 1997; revisions received Feb 11, 1998, and Apr 28, 1998; accepted May 7, 1998. Reprint requests: Pietro Vajro, MD, Dipartimento di Pediatria, Facolta’ di Medicina e Chirurgia, Uni- versita’ di Napoli “Federico II”, Via Pansini 5, 80131 Napoli, Italy. Copyright © 1998 by Mosby, Inc. 0022-3476/98/$5.00 + 0 9/22/91650 LDL Low-density lipoprotein macroAST Aspartate aminotransferase macroenzyme PEG Polyethylene glycol VLDL Very low-density lipoprotein Ten children with asymptomatic persistent cryptogenic increased serum levels of aspartate aminotransferase (AST) were screened for detection and monitor- ing of AST macroenzyme (macroAST). MacroAST was found in 4 patients; their serum AST levels were significantly higher than in those without biochem- ical evidence of macroAST (mean ± SD: 515 ± 433 and 78 ± 16 IU/L, respec- tively; P = .0095). MacroAST was a persistent, benign phenomenon and was probably not congenital. (J Pediatr 1998;133:286-9)