This study tested the hypothesis that gamma-glutamyl transferase (GGT) can be used as a reliable biomarker to distinguish skeletal muscle from liver damage. Twenty-eight Duchenne muscular dystrophy subjects with proven dystrophin gene mutations were enrolled. Included were 14 ambulatory and 14 nonambulatory patients with approximately half of each cohort taking corticosteroids. Twenty normal males served as controls. Initial blood samples for serum GGT and creatine kinase were taken between 8AM and 9AM and redrawn 8 hours later to test for variability. Between blood draws, subjects resumed normal activities in a play environment or could leave the clinic. Not a single duchenne muscular dystrophy patient showed a GGT outside the control range at any time point, while creatine kinase levels were 14 to 200 times normal. Validation of this finding is essential for management of patients with muscle disorders exposed to potentially hepatotoxic drugs for clinical management or monitoring subjects participating in clinical trials.
Pearce JM, Pennington RJ, Walton JNSerum enzyme studies in muscle disease. II. Serum creatine kinase activity in muscular dystrophy and in other myopathic and neuropathic disorders. J Neurol Neurosurg Psychiatry. 1964;27:96-99.
2.
Somer H., Donner M., Murros J., Konttinen A.A serum isozyme study in muscular dystrophy. Particular reference to creatine kinase, aspartate aminotransferase, and lactic acid dehydrogenase isozymes . Arch Neurol. 1973;29:343-345.
3.
Rutledge J., Andersen J., Fink CW, et al. Persistent hypertransaminasemia as the presenting finding of childhood muscle disease. Clin Pediatr. 1985 ;24:500-503.
4.
Cao A., De Virgiliis S., Lippi C., Coppa G.Serum and muscle creatine kinase isoenzymes and serum aspartate aminotransferase isoenzymes in progressive muscular dystrophy. Enzyme. 1971; 12:49-62.
5.
Lin YC, Lee WT, Huang SF, et al. Persistent hypertransaminasemia as the presenting findings of muscular dystrophy in childhood. Acta Paediatr Taiwan. 1999;40:424-429.
6.
Begum T., Oliver MR, Kornberg AJ, Dennett X.Elevated aminotransferase as a presenting finding in a patient with occult muscle disease. J Paediatr Child Health. 2000 ;36:189-190.
7.
Korones DN, Brown MR, Palis J. "Liver function tests" are not always tests of liver function. Am J Hematol. 2001;66:46-48.
8.
Urganci N., Arapoglu M., Serdaroglu P., Nuhoglu A.Incidental raised transaminases: a clue to muscle disease. Ann Trop Paediatr. 2006;26:345-348.
9.
Zatz M., Rapaport D., Vainzof M., et al. Serum creatine-kinase (CK) and pyruvate-kinase (PK) activities in Duchenne (DMD) as compared with Becker (BMD) muscular dystrophy. J Neurol Sci. 1991;102:190-196.
10.
Abraham S., Begum S., Isenberg D.Hepatic manifestations of autoimmune rheumatic diseases. Ann Rheum Dis. 2004;63: 123-129.
Miller EB, Shichmanter R., Friedman JA, Sokolowski N.Granulomatous hepatitis and Sjogren's syndrome: an association. Semin Arthritis Rheum. 2006;36:153-158.
13.
Akesson A., Berglund K., Karlsson M.Liver function in some common rheumatic disorders. Scand J Rheumatol. 1980;9:81-88.
14.
Rain F., Durieu I., Mackiewitz R., Levrat R.Dermatopolymyositis and primary biliary cirrhosis. A rare association. Presse Med.1996;25:581-582.
15.
Ytterberg SRTreatment of refractory polymyositis and dermatomyositis . Curr Rheumatol Rep. 2006;8:167-173.
16.
Kim P., Grossman JMTreatment of mixed connective tissue disease. Rheum Dis Clin North Am. 2005;31:549-565.
17.
Kissel JT, Levy RJ, Mendell JR, Griggs RCAzathioprine toxicity in neuromuscular disease. Neurology . 1986;36:35-39.
18.
White MG, Stoward PJ, Christie KN, Anderson JMProteases in normal and diseased human skeletal muscle: a preliminary histochemical survey. Histochem J. 1985;17:819-832.
19.
Mokri B., Engel AGDuchenne dystrophy: electron microscopic findings pointing to a basic or early abnormality in the plasma membrane of the muscle fiber. Neurology . 1975;25:1111-1120.
20.
McCarter GC , Steinhardt RAIncreased activity of calcium leak channels caused by proteolysis near sarcolemmal ruptures. J Membr Biol . 2000;176:169-174.
21.
Matsumoto T. , Yoshimine T., Shimouchi K., et al. The liver in systemic lupus erythematosus: pathologic analysis of 52 cases and review of Japanese Autopsy Registry Data . Hum Pathol. 1992;23:1151-1158.
22.
Farrell GCDrugs and steatohepatitis. Semin Liver Dis. 2002;22:185-194.
Mendell JR, Moxley RT, Griggs RC, et al. Randomized, double-blind six-month trial of prednisone in Duchenne's muscular dystrophy. N Engl J Med. 1989;320:1592-1597.
25.
Moxley RT 3rd, Ashwal S., Pandya S., et al. Practice parameter: corticosteroid treatment of Duchenne dystrophy: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2005;64:13-20.
26.
Moore SA, Shilling CJ, Westra S., et al. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol. 2006; 65:995-1003.
27.
Domenico B. , Ruzza G., Bonometto P., et al. A multicenter, double-blind, randomized trial of deflazacort versus prednisone in Duchenne muscular dystrophy. Muscle Nerve. 2000;23:1344-1347.
28.
Kohli R., Harris DC, Whitington PFRelative elevations of serum alanine and aspartate aminotransferase in muscular dystrophy. J Pediatr Gastroenterol Nutr. 2005 ;41:121-124.
29.
Cepelak I., Zanic Grubisic T., Mandusic A., et al. Valproate and carbamazepine comedication changes hepatic enzyme activities in sera of epileptic children. Clin Chim Acta. 1998;276:121-127.
30.
Harasymiw JW , Vinson DC, Bean P.The early detection of alcohol consumption (EDAC) score in the identification of heavy and at-risk drinkers from routine blood tests. J Addict Dis. 2000;19:43-59.
31.
Peng WK, Sheikh Z., Paterson-Brown S., Nixon SJRole of liver function tests in predicting common bile duct stones in acute calculous cholecystitis. Br J Surg. 2005;92:1241-1247.
32.
Rezzani R.Cyclosporine A and adverse effects on organs: histochemical dies. Prog Histochem Cytochem. 2004;39:85-128.
