T.P.27: Diagnostic power of the non-ischemic forearm exercise test in glycogenosis type V

Abstract

In the past fifteen years, more than 1200 patients underwent the non-ischemic forearm exercise test (NIFET) in our referral center as a first screening tool for the detection of metabolic myopathies. Finally 40 patients were diagnosed so far with a McArdle disease (glycogenosis type V). As a consequence of the absence of phosphorylase enzyme, no rise of lactate and an elevated rise of ammonia are generally described after exercise. The aim of this retrospective study was to formally assess the results of the NIFET to determine optimal diagnostic criteria as the first screening instrument in the diagnostic process in McArdle disease (sensitivity), and to check if other diagnoses were inferred using these diagnostic criteria (specificity). Forty patients with McArdle disease were definitively diagnosed; 21 were males, 19 females. They were aged between 8 and 72years. The mean age of diagnosis was 35.6±16.1years. Most of them had muscle complaints since their childhood. Half of them experienced at least one episode of rhabdomyolysis in their life marked by dark urine. Finally all the patients had previous elevated CK levels above 500IU/L and recognized the second wind phenomenon, which is pathognomonic for McArdle disease. Diagnosis was confirmed by genetic analysis of the PYGM gene. Three quarters of the patients were homozygous or compound heterozygous for the most frequent p.Arg50X mutation. Four novel mutations were revealed. A lactate rise <1.0mmol/L and an ammonia rise >40μmol/L discriminated all the McArdle patients from normal subjects. Three patients with glycogenosis type III were also found with these values. A sensitivity and specificity of respectively 100 % and 99.8% were calculated. The safety of the test was confirmed by the fact that the 24H-CK level showed no significant difference of the CK level at the day of the test. This retrospective analysis proves that the NIFET is safe and highly efficient for the detection of McArdle disease with no false positive results.