Natural history of serum creatine kinase levels and motor, pulmonary, and cardiac functions in 337 patients with Duchenne muscular dystrophy: a retrospective study at a single referral center in Japan

Abstract

AbstractIntroduction/AimsDuchenne muscular dystrophy (DMD) presents with skeletal muscle weakness, followed by respiratory and cardiac muscle involvement. Recently, with the development of treatments, the need for a natural history to serve as a control for determining treatment efficacy in clinical trials has increased dramatically, however, few large-scale studies have investigated changes in these symptoms. The present study examined the natural history of Japanese DMD patients as a whole and individual patient with genetic mutations eligible for exon skipping therapy.MethodsMedical records of 337 patients with DMD who visited Kobe University Hospital over a period of 30 years from their first visit until 20 years of age were examined.ResultsSerum creatine kinase levels showed a stair-step pattern of decline, with extremely high values until 6 and a rapid decline from 7 to 12 years of age. Both the median 10-meter run/walk velocity and rise-from-floor velocity peaked at the age of 4 years and declined with age. The values for respiratory function declined from the age of 11 years. The median left ventricular ejection fraction was >60% until the age of 12 years and rapidly declined from 13 to 15 years of age. Examination of the relationship between gene mutations eligible for exon-skipping therapy and natural history revealed no characteristic findings.DiscussionWe found that creatine kinase levels and motor, respiratory, and cardiac functions each exhibited unique changes over time. These findings will be useful in developing new therapeutic agents for DMD and in determining their efficacy in clinical trials.