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Clin Chim Acta. 2018 Mar;478:171-181. doi: 10.1016/j.cca.2017.12.036. Epub 2017 Dec 24.

Perturbation of muscle metabolism in patients with muscular dystrophy in early or acute phase of disease: In vitro, high resolution NMR spectroscopy based analysis.

Author information

1
Department of Neurology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, U.P., India; School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India. Electronic address: neeraj.sinha@cbmr.res.in.
2
Department of Neurology, UP University of medical sciences, Saifai, Etawah, UP 206130, India.
3
School of Life Sciences, Jawaharlal Nehru University, New Delhi 110067, India.
4
Center of Biomedical Research, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226014, U.P., India.

Abstract

BACKGROUND:

Muscular dystrophy is an inherited muscle disease, characterized by progressive muscle wasting and weakness of variable distribution and severity.

METHODS:

In vitro, high-resolution proton nuclear magnetic resonance (NMR) spectroscopy based analysis was performed on perchloric acid (PCA) extract of muscle specimens of patients suffering from various types of muscular dystrophies to identify alteration in hydrophilic low-molecular weight substances (aqueous metabolites) as compared to muscle of control subjects as well as in between the types of muscular dystrophy. Muscle tissue specimens were obtained from Duchenne muscular dystrophy (DMD) [n=11], Becker muscular dystrophy (BMD) [n=12], facioscapulohumeral dystrophy (FSHD) [n=9] and limb girdle muscular dystrophy (LGMD)-2B [n=22]. Control muscle specimens [n=40] were also taken.

RESULTS:

Concentration of branched chain amino acids (BCA), glutamine/glutamate (Gln/Glu), acetate (Ace) and fumarate (Fum) was decreased and His was increased in muscle tissue of DMD, BMD, FSHD and LGMD-2B patients as compared to control subjects. Alanine (Ala) was significantly reduced in BMD, FSHD and LGMD-2B patients as compared to control subjects. Tyrosine (Tyr) was present only in the muscle tissue of control subjects. Propionate (Prop) was present in muscle tissue of DMD, BMD, FSHD and LGMD-2B patients and was absent in muscle tissue of control subjects. Concentration of BCA and Prop is significantly reduced in patients with DMD as compared to BMD, but Glucose is significantly higher in patients with DMD as compared to BMD. Quantity of Glucose, His and Gln/glu are significantly higher in patients with DMD as compared to FSHD, but Prop is significantly reduced in patients with DMD as compared to FSHD. Concentration of Ala and His is significantly higher in patients with DMD as compared to LGMD-2B, but BCA, Glucose and Prop are significantly reduced in patients with DMD as compared to LGMD-2B. Concentration of His is significantly higher in patients with BMD as compared to FSHD. Concentration of His is significantly reduced and Glucose is higher in patients with LGMD-2B as compared to BMD. Glucose concentration is significantly reduced in patients with FSHD as compared to LGMD-2B. ROC curves supported the noticeable discrimination in between the patients with DMD and FSHD for the quantity of Gln/Glu, and patients with LGMD-2B and DMD for the quantity of Ala. Collectively, these findings showed the perturbation of muscle metabolism in muscular dystrophy.

CONCLUSIONS:

The data of presented study may be used as supporting information for existing methods of the diagnosis for patients with muscular dystrophy.

KEYWORDS:

Aqueous metabolites; Metabolic alteration; Metabolism; Metabolomics; Muscle; Muscular dystrophy; NMR spectroscopy; Perchloric acid extract; Tissue

PMID:
29278724
DOI:
10.1016/j.cca.2017.12.036
[Indexed for MEDLINE]

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