Searching for Clues in the Diagnosis of McArdle Disease

Introduction McArdle disease (glycogen storage disorder type 5) is an autosomal recessive metabolic myopathy caused by a myophosphorylase enzyme deficiency. Most patients develop symptoms during childhood; however, diagnosis is usually delayed until adulthood. Our study aimed to identify clues for an earlier recognition of this rare disease. Materials and methods This is a retrospective case series of 15 patients with McArdle syndrome, as diagnosed histologically and/or genetically, who were evaluated at the Cleveland Clinic Neurologic Institute. Data related to demographics, symptoms, exam findings, laboratory test results, genetic testing, muscle biopsy, and prior misdiagnoses were analyzed. Results Fifteen patients with McArdle disease were identified with a median age at symptom onset of 20 years (IQR=11.5-31.25). Symptoms included exertional myalgia and fatigue in all patients (n=15) and the second wind phenomenon in 53% (n=8). Creatine kinase (CK) values were elevated in 930/931 measurements (range 273-75510 IU/L), and myoglobinuria was seen in 60% (n=9). All patients exhibited significant fluctuations in CK, defined as a maximum-to-minimum ratio greater than 5 (ratio range: 5.4-276.6, median ratio: 20.4). Electromyographies (EMGs) were normal in 33% (n=5/15). Median age at diagnosis was 34 years (IQR=28-42). Median delay in diagnosis was 11 years (IQR=5-17). Ten patients (67%) were initially misdiagnosed, and the most common misdiagnosis was autoimmune myositis (n=5, 33%). Conclusions A lack of or underreporting of myoglobinuria or the second wind phenomenon by the patients can lead to a delay in the diagnosis of McArdle disease. Persistently elevated baseline CK without objective weakness and at times dramatically fluctuating CK levels are important diagnostic clues. Physical exam and EMG are often non-diagnostic. Increased awareness of this condition is critical to avoid misdiagnoses.