Urinary titin reflects the severity of walking ability, muscle strength, and muscle and cardiac damage in patients with Becker muscular dystrophy

Hiroyuki Awano; Yoshinori Nambu; Kayo Osawa; Taku Shirakawa; Tsuyoshi Matsumura; Akiko Wakisaka; Satoshi Kuru; Michinori Funato; Yasuhiro Takeshima; Keiko Ishigaki; Michio Kobayashi; Tatsuharu Sato; Tatsuya Fujii; Kazuma Sugie; Koichi Kimura; Hirofumi Komaki; Akinori Nakamura; Masafumi Matsuo

doi:10.1016/j.cca.2024.120053

Urinary titin reflects the severity of walking ability, muscle strength, and muscle and cardiac damage in patients with Becker muscular dystrophy

Clin Chim Acta. 2024 Nov 17:120053. doi: 10.1016/j.cca.2024.120053. Online ahead of print.

Authors

Hiroyuki Awano¹, Yoshinori Nambu², Kayo Osawa³, Taku Shirakawa³, Tsuyoshi Matsumura⁴, Akiko Wakisaka⁵, Satoshi Kuru⁶, Michinori Funato⁷, Yasuhiro Takeshima⁸, Keiko Ishigaki⁹, Michio Kobayashi¹⁰, Tatsuharu Sato¹¹, Tatsuya Fujii¹², Kazuma Sugie¹³, Koichi Kimura¹⁴, Hirofumi Komaki¹⁵, Akinori Nakamura¹⁶, Masafumi Matsuo¹⁷

Affiliations

¹ Research Initiative Center, Organization for Research Initiative and Promotion, Tottori University, Yonago, Japan. Electronic address: [email protected].
² Department of Pediatrics, Kobe University Graduate School of Medicine, Kobe, Japan.
³ Faculty of Health Sciences, Kobe Tokiwa University, Kobe, Japan.
⁴ Department of Neurology, NHO Osaka Toneyama Medical Center, Toyonaka, Japan.
⁵ Department of Pediatrics, NHO Iou National Hospital, Kanazawa, Japan.
⁶ Department of Neurology, NHO Suzuka National Hospital, Suzuka, Japan.
⁷ Department of Pediatric Neurology, NHO Nagara Medical Center, Nagara, Japan.
⁸ Department of Pediatrics, Hyogo Medical University School of Medicine, Nishinomiya, Japan.
⁹ Department of Pediatrics, Tokyo Women's Medical University School of Medicine, Tokyo, Japan.
¹⁰ Department of Neurology, NHO Akita National Hospital, Yurihonjo, Japan.
¹¹ Department of Pediatrics, Nagasaki University Hospital, Nagasaki, Japan.
¹² Department of Pediatrics, Shiga Medical Center for Children, Moriyama, Japan.
¹³ Department of Neurology, Nara Medical University School of Medicine, Kashihara, Japan.
¹⁴ Department of Laboratory Medicine/Cardiology, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
¹⁵ Department of Child Neurology, National Center Hospital, National Center of Neurology and Psychiatry, Tokyo, Japan.
¹⁶ Department of Neurology, NHO Matsumoto Medical Center, Matsumoto, Japan.
¹⁷ Graduate School of Science, Technology and Innovation, Kobe University, Kobe, Japan.

PMID: 39561886
DOI: 10.1016/j.cca.2024.120053

Abstract

Background: Becker muscular dystrophy (BMD) is a dystrophinopathy caused by a pathological variant of the DMD gene. Urinary titin, a degradation product of the giant protein titin present in muscle sarcomeres, has been used as a biomarker to reflect muscle degradation in Duchenne muscular dystrophy, a more severe dystrophinopathy. However, the clinical significance of urinary titin levels in BMD remains unclear. This study aimed to investigate the relationship between urinary titin levels and the clinical data in patients with BMD.

Methods: Urine samples were collected from 123 patients with BMD, and urinary titin levels were measured. The association of urinary titin with clinical data, including age, physical measurements, physical activity, blood tests, and cardiopulmonary test results, was examined.

Results: A total of 257 urine samples were obtained from patients of 5-79 years of age. The median urinary titin level was 72.6 pmol/mg Cr (range 0.2-4325.0 pmol/mg Cr). No strong correlation was found between urinary titin levels and age, physical measurements, physical function, blood test results, or cardiopulmonary function. However, on comparing clinical data between the age-matched high urinary titin (N = 94) and normal (N = 29) groups, the high urinary titin group had a significantly greater number of non-ambulatory cases (23.9 % vs. 3.6 %), weaker grip strength (16.3 vs. 32.0 kg), and higher serum creatine kinase (1072 vs. 398 U/L) and cardiac troponin I (10.6 vs. 2.5 pg/mL) levels.

Conclusion: Urinary titin was identified as a biomarker reflecting walking ability, muscle strength, and skeletal and cardiac damage in patients with BMD.

Keywords: Becker muscular dystrophy; Biomarker; Urinary titin.