Serum Creatinine Distinguishes Duchenne Muscular Dystrophy from Becker Muscular Dystrophy in Patients Aged ≤3 Years: A Retrospective Study.

Liang Wang,Juan Yang,Jiqing Cao,Lulu Xiao,Cheng Zhang,Huili Zhang,Menglong Chen,Yiming Sun,Ruojie He

doi:10.3389/fneur.2017.00196

Abstract

Here, we investigated correlations between serum creatinine (SCRN) levels and clinical phenotypes of dystrophinopathy in young patients. Sixty-eight patients with dystrophinopathy at the Neuromuscular Clinic, The First Affiliated Hospital, Sun Yat-sen University, were selected for this study. The diagnosis of dystrophinopathy was based on clinical manifestation, biochemical changes, and molecular analysis. Some patients underwent muscle biopsies; SCRN levels were tested when patients were ≤3 years old, and reading frame changes were analyzed. Each patient was followed up, and motor function and clinical phenotype were assessed when the same patients were ≥4 years old. Our findings indicated that in young patients, lower SCRN levels were associated with increased disease severity (p < 0.01) and that SCRN levels were the highest in patients exhibiting mild Becker muscular dystrophy (BMD) (p < 0.001) and the lowest in patients with Duchenne muscular dystrophy (DMD) (p < 0.01) and were significantly higher in patients carrying in-frame mutations than in patients carrying out-of-frame mutations (p < 0.001). SCRN level cutoff values for identifying mild BMD [18 µmol/L; area under the curve (AUC): 0.947; p < 0.001] and DMD (17 µmol/L; AUC: 0.837; p < 0.001) were established. These results suggest that SCRN might be a valuable biomarker for distinguishing DMD from BMD in patients aged ≤3 years and could assist in the selection of appropriate treatment strategies.

Highlights

Dystrophinopathy is a recessive X-linked hereditary disease with an incidence of 1 in 3,500 newborn males, characterized by progressive muscle weakness, atrophy, and loss of ambulation [1]
Our findings indicated that in young patients, lower serum creatinine (SCRN) levels were associated with increased disease severity (p < 0.01) and that SCRN levels were the highest in patients exhibiting mild Becker muscular dystrophy (BMD) (p < 0.001) and the lowest in patients with Duchenne muscular dystrophy (DMD) (p < 0.01) and were significantly higher in patients carrying in-frame mutations than in patients carrying out-of-frame mutations (p < 0.001)
Different DMD mutations result in two primary forms of defective dystrophin: a truncated, non-functional protein associated with DMD and a partially functional protein associated with BMD [4]

Summary

Introduction

Dystrophinopathy is a recessive X-linked hereditary disease with an incidence of 1 in 3,500 newborn males, characterized by progressive muscle weakness, atrophy, and loss of ambulation [1]. The disease can be divided into two clinical phenotypes according to different courses: Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD). DMD exhibits rapid progression and loss of ambulation prior to age 12, whereas BMD exhibits relatively mild symptoms with slower progression. As technology impro ves, new prospective treatments are proposed, such as stem cell therapy and gene therapy, including exon skipping and stop codon readthrough therapy [6,7,8]. Issues such as side effects and high costs remain unresolved [9]. As early treatment initiation leads to improved outcomes, identifying specific clinical phenotypes in young patients is essential for selecting appropriate treatments [10]

Methods

Results

Conclusion