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Myasthenia gravis (MG) is an acquired disorder of neuromuscular transmission caused by the binding of pathogenic autoantibodies to muscle's postsynaptic nicotinic acetylcholine receptor (AChR). In about 3% of cases the pathogenic antibody is directed at the functionally associated muscle-specific receptor tyrosine kinase (MuSK). The outcome is a critical loss of the AChR channel protein, which is required to activate the muscle action potential.
Amongst North American Caucasian children (ie, aged 1-18), MG affects prepubertal boys and girls with equal frequency. Spontaneous remissions are relatively frequent. Females predominate (4.5:1) after puberty. Amongst black children with MG, females predominate (2:1) in all age groups, and remissions are infrequent, regardless of therapy.
Congenital MG is a hereditary nonautoimmune disorder characterized by defects In AChR or other synaptic proteins.
Autoimmune serology is indispensable for both initial evaluation and monitoring the course of patients with acquired disorders of neuromuscular transmission. The neurological diagnosis depends on the clinical context, electromyographic findings, and response to anticholinesterase administration. MG is confirmed more readily by a serological profile than by any single test.
See Myasthenia Gravis: Pediatric Diagnostic Algorithm in Special Instructions.
Recommended for initial investigation of patients presenting at less than age 20 with a defect of neuromuscular transmission
Confirming that a recently acquired neurological disorder has an autoimmune basis
Distinguishing acquired myasthenia gravis from congenital myasthenic syndromes (persistently seronegative)
Providing a quantitative baseline for future comparisons in monitoring clinical course and response to immunomodulatory treatment
Note: Single antibody tests may be requested in follow-up of patients with positive results documented in this laboratory.
Muscle acetylcholine receptor (AChR) autoantibodies are characteristic but not diagnostic of myasthenia gravis (MG). They are found in 13% of patients with Lambert-Eaton Syndrome (LES), which is rare in children. The patient's autoantibody profile is more informative than the result of any single test for supporting a diagnosis of MG.
Titers of AChR antibodies are generally higher in patients with severe weakness, but severity cannot be predicted by antibody titer. Seronegativity is more frequent in children with prepubertal onset of acquired MG (33%-50%) than in adults (<10%). Thymoma is rare under age 20, and striational antibodies (see STR / Striational [Striated Muscle] Antibodies, Serum) also are rare, except in the context of MG related to neoplasia (usually thymoma or neuroblastoma), graft-versus-host disease, autoimmune liver disease, or D-penicillamine therapy. This laboratory has recently noted muscle-specific receptor tyrosine kinase antibody in children with "seronegative" acquired MG, but the frequency of this antibody in pediatric MG has not been determined.
A positive result in this evaluation is not per se diagnostic of myasthenia gravis (MG). Positive values for muscle acetylcholine receptor (AChR) antibodies occur in 10% of Lambert-Eaton syndrome patients, in children with graft-versus-host disease, and recipients of D-penicillamine (with and without clinically evident MG), and in children with paraneoplastic neurological disorders related to neuroblastoma, thymoma, and chondroblastoma (ie, seropositivity is not restricted to MG). Children with autoimmune liver disorders may be anticipated, like adults, to have unexplained AChR or striational antibodies (data not available).
Seronegativity does not exclude the diagnosis of autoimmune MG.
A minority of patients lacking detectable AChR antibodies have the recently discovered muscle-specific receptor tyrosine kinase antibodies.
In this laboratory, false-positive results for AChR binding antibody are excluded by routinely retesting positive sera with (125)I-alpha-bungarotoxin in the absence of muscle AChR. False-positive results occur most frequently in the bioassay for AChR modulating antibody; serum redraw will be requested when only this assay yields a positive result. AChR blocking antibody is the least frequently encountered AChR antibody specificity, and is never positive with a negative AChR modulating value. Curare-like drugs used during general anesthesia can yield a false-positive AChR blocking antibody result.
Seropositive rates differ in different laboratories.
This test should not be requested in patients who have recently received radioisotopes, therapeutically or diagnostically, because of potential assay interference. The specific waiting period before specimen collection will depend on the isotope administered, the dose given and the clearance rate in the individual patient. Specimens will be screened for radioactivity prior to analysis. Radioactive specimens received in the laboratory will be held one week and assayed if sufficiently decayed, or canceled if radioactivity remains.
ACh RECEPTOR (MUSCLE) BINDING ANTIBODY
< or =0.02 nmol/L
ACh RECEPTOR (MUSCLE) MODULATING ANTIBODIES
0-20% (reported as __% loss of AChR)
1. Andrews PI, Massey JM, Howard JF Jr, Sanders DB: Race, sex, and puberty influence onset, severity, and outcome in juvenile myasthenia gravis. Neurology 1994 July;44(7):1208-1214
2. Lennon VA: Serological profile of myasthenia gravis and distinction from the Lambert-Eaton myasthenic syndrome. Neurology 1997;48(Suppl 5):S23-S27
3. Hoch W, McConville J, Helms S, et al: Auto-antibodies to the receptor tyrosine kinase MuSK in patients with myasthenia gravis without acetylcholine receptor antibodies. Nat Med 2001 Mar;7(3):365-368
4. Joshi DD, Anderson PM, Matsumoto J, et al: Metastatic chondroblastoma with elevated creatine kinase and paraneoplastic neurologic autoimmunity. J Pediatr Hematol Oncol 2003;25:900-904