ABSTRACT
We report two patients in whom phosphoglycerate mutase (PGAM) deficiency was associated with the triad of exercise-induced cramps, recurrent myoglobinuria, and tubular aggregates in the muscle biopsy. Serum creatine kinase (CK) levels were elevated between attacks of myoglobinuria. Forearm ischemic exercise tests produced subnormal increases of venous lactate. Muscle biopsies showed subsarcolemmal tubular aggregates in type 2 fibers. Muscle PGAM activities were markedly decreased (3% of the normal mean) and molecular genetic studies showed that both patients were homozygous for a described missense mutation (W78X). A review of 15 cases with tubular aggregates in the muscle biopsies from our laboratory and 15 cases with PGAM deficiency described in the literature showed that this clinicopathological triad is highly suggestive of PGAM deficiency.
Subject(s)
Exercise Tolerance/genetics , Muscle, Skeletal/enzymology , Muscular Diseases/enzymology , Myoglobinuria/enzymology , Phosphoglycerate Mutase/deficiency , Adolescent , Adult , Black or African American/genetics , Biopsy , Creatine Kinase/blood , DNA Mutational Analysis , Exercise Test , Female , Humans , Inclusion Bodies/enzymology , Inclusion Bodies/genetics , Inclusion Bodies/pathology , Ischemia/enzymology , Ischemia/genetics , Ischemia/physiopathology , Male , Middle Aged , Muscle Cramp/enzymology , Muscle Cramp/genetics , Muscle Cramp/physiopathology , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Muscular Diseases/diagnosis , Muscular Diseases/genetics , Mutation, Missense , Myoglobinuria/genetics , Myoglobinuria/physiopathology , Phosphoglycerate Mutase/genetics , Sarcoplasmic Reticulum/enzymology , Sarcoplasmic Reticulum/pathologyABSTRACT
Various parameters of the repetitive nerve stimulation (RNS) test of the abductor digiti quinti muscle were analyzed statistically in 34 patients with Lambert-Eaton myasthenic syndrome (LEMS). The sensitivity and specificity of the increments after exercise and after 50-HZ stimulation for the diagnosis of LEMS were compared with reference values in 40 normal subjects and data from 538 tests in patients with myasthenia gravis (MG). When we used a 100% increment (the "gold standard") as the normal limit for the postexercise facilitation (PEF) or the high-rate stimulation (HRS) test, the diagnosis of LEMS was confirmed in 29 (85%) cases. When a 60% increment was used as the normal limit, the diagnosis of LEMS was made in 97% of cases. In MG, a 60% increment was observed in only 4 of 538 cases by HRS and in none by the exercise test. Thus, the use of a 60% increment showed a sensitivity of 97% for the diagnosis of LEMS and a specificity of 99% in excluding MG. A 60% increment in either the PEF or HRS test for the diagnosis of LEMS is a desirable alternative to the 100% increment previously considered to be the gold standard for this diagnosis.
