Myopathy with Pure Adolase Elevation
Myopathy with Pure Adolase Elevation
Abstract & commentary
By Michael Rubin, MD, Professor of Clinical Neurology, Weill Cornell Medical College. Dr. Rubin reports that he receives grant/research support from Pfizer and is on the speaker's bureau of Athena Diagnostics.
Synopsis: Isolated elevation of serum aldolase, with a clinical syndrome of myopathy, is a distinct disorder that predicts perimysial muscle pathology.
Source: Nozaki K, Pestronk A. High aldolase with normal creatine kinase in serum predicts a myopathy with perimysial pathology. J Neurol Neurosurg Psychiatry doi:10.1136/jnnp.2008.161448.
Is serum aldolase elevation, without serum creatine kinase (CK) abnormality, of diagnostic specificity among patients suspected of having myopathy? Review of neuromuscular records from Washington University, St. Louis, MO, between October 1998 and March 2008 identified 12 patients with elevated aldolase and normal CK. Elevated aldolase was present in nine patients at presentation and in three during a neuromuscular flair. CK had been elevated in a single patient six years earlier but was documented to be normal during the previous two years. All patients underwent laboratory testing for myositis-specific serum antibodies, electrodiagnostic studies, and deltoid (n = 7) or quadriceps (n = 5) biopsy. Muscle pathology was compared to 75 abnormal muscle biopsies with autoimmune syndromes and 14 biopsies with serum anti-Jo-1 antibodies. Statistical analysis was undertaken using Fisher's exact tests and differences with p < 0.01 were deemed significant.
Ranging in age from 5 to 60 years, there were six men and six women, 10 Caucasian and one each of Black and Hispanic origin, all with recent onset of symptoms. Neuromuscular symptoms included myalgias or cramps (92%); mild to moderate weakness, usually diffuse, symmetric, and affecting proximal and distal arm and leg muscles (50%); and systemic complaints including joint pain (75%), skin and pulmonary involvement, and immune disorders. Dermatologic features, seen in 75%, included rashes resembling dermatomyositis, graft-vs.-host reactions, and poor wound healing. Dyspnea, cough, and pulmonary fibrosis on imaging studies encompassed the pulmonary involvement, while systemic immune disorders included eosinophilia, graft-vs.-host disease, myasthenia gravis, dermatomyositis, rheumatoid arthritis, and vasculitis. None were found to have neoplastic disease and, of those given corticosteroid therapy, all improved. Aldolase ranged from 9–21 (nl < 8) and CK was usually well within the normal range. Needle EMG was normal in four, but myopathic motor units, with or without spontaneous activity, were seen in the remainder. Perimysial muscle pathology was present in 92% (n = 11), and included acid phosphatase positive cells (83%), connective tissue fragmentation (75%), and perimysial alkaline phosphatase staining (58%). Foci of CD4 positive mononuclear cells were seen in 50%, equally divided between the endomysium or perivascular regions. MHC Class 1 up-regulation was the most common form of muscle pathology (83%), but routine histochemistry revealed perifascicular atrophy, necrosis and regeneration, or reduced COX staining in 58%, and small vessel pathology was present in 17%, including C5b-9 deposition and reduced capillary numbers. Compared to immune myopathy controls, only connective tissue fragmentation and acid phosphatase positive cellularity were seen more commonly in aldolase positive patients, and no differences were discerned histochemically compared to Jo-1 antibody-positive control biopsies. Elevated aldolase in the absence of CK abnormality bespeaks perimysial myopathology, akin to that seen with anti-synthetase antibodies.
Commentary
In addition to CK and aldolase, ALT (alanine aminotransferase), AST (aspartate aminotransferase), and LDH are other serum markers useful in monitoring myopathy, with most patients demonstrating at least one elevated enzyme at some point during their illness. Carbonic anhydrase III, found exclusively in skeletal muscle, may also increase in myositis but is not readily available. Troponin, composed of three proteins (C, I, and T), is a structural component of muscle thin filaments. Skeletal troponin I correlates well with CK, making it a yet-to-be-validated marker for myopathy. Cardiac troponin I does not correlate with CK or other measures of skeletal muscle injury but cardiac troponin T is frequently elevated with myositis (2.5% vs. 41%).
Reference
1. Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am 2002;28:859-890.
Isolated elevation of serum aldolase, with a clinical syndrome of myopathy, is a distinct disorder that predicts perimysial muscle pathology.Subscribe Now for Access
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