1.
Fibroblast growth factor 21 is a sensitive biomarker of mitochondrial disease.
Davis, RL, Liang, C, Edema-Hildebrand, F, Riley, C, Needham, M, Sue, CM
Neurology. 2013;(21):1819-26
Abstract
OBJECTIVE To prospectively determine the reliability and validity of serum fibroblast growth factor 21 (FGF-21) as a biomarker for mitochondrial disease in a cross-sectional cohort of adults with mitochondrial disease from a specialist primary care and tertiary referral clinic. METHODS We recruited 140 subjects, including 54 adults with mitochondrial disease, 20 patients with nonmitochondrial neuromuscular disease, and 66 control subjects, between November 2011 and October 2012. We compared serum FGF-21 concentrations to classical biomarkers, serum creatine kinase, lactate, pyruvate, and lactate to pyruvate ratio, to determine its validity and reliability as a biomarker of mitochondrial disease. We determined the sensitivity, odds ratio (OR), and overall reliability of FGF-21 as a marker of mitochondrial disease using statistical analyses. RESULTS Median serum FGF-21 concentrations were significantly elevated in patients with mitochondrial disease and differed significantly between all experimental groups. FGF-21 showed a markedly higher diagnostic OR (45.7 [95% confidence interval = 12.6-166.5], p < 0.0001) when compared to other biomarkers and was the best predictor of disease according to sensitivity and receiver operating characteristic curve analysis. After multivariate logistic regression analysis controlling for potential confounders, FGF-21 was the only measured parameter capable of predicting mitochondrial disease. CONCLUSION This prospective study establishes serum FGF-21 levels as a sensitive biomarker of mitochondrial disease and demonstrates that they are the best predictor of this disorder when compared to serum levels of classical indicators: creatine kinase, lactate, pyruvate, and the lactate to pyruvate ratio.
2.
[Diagnosis of a myopathic disease in adult].
Eymard, B
La Revue du praticien. 2008;(20):2229-43
Abstract
Strategy for the diagnosis of a muscle weakness includes two steps: to rely the weakness to a muscular origin and to find the aetiology. A muscular deficit is purely motor, without sensory signs, involving mainly axial and proximal muscles. The essential informations for aetiological characterization are: 1st) a family history, indicating a genetic origin, 2nd the chronological profile, 3rd) the clinical pattern (deficit topography, modification of muscle volume, fatigability, contractures, myotonia, oculobulbar, respiratory or cardiac involvement), 4th) investigations (CK level, EMG, muscle imaging muscle, biopsy, genetic testing). Two autosomal dominant myopathies begin in adulthood: Steinert's myotonic dystrophy characterized by myotonia facial and distal weakness and atrophy, plurisystemic involvement and facio-scapulo-peroneal dystrophy with asymmetric facial and scapulo-humeral weakness. If the evolution is rapid and family history absent, a curable myopathy (inflammatory, toxic, iatrogenic, and endocrine) is to be looked for. Inclusion body myositis is the most frequent myopathy after the age of 50 years.
3.
Caveolinopathies: mutations in caveolin-3 cause four distinct autosomal dominant muscle diseases.
Woodman, SE, Sotgia, F, Galbiati, F, Minetti, C, Lisanti, MP
Neurology. 2004;(4):538-43
Abstract
The caveolin-3 protein is expressed exclusively in muscle cells. Caveolin-3 expression is sufficient to form caveolae-sarcolemmal invaginations that are 50 to 100 nm in diameter. Monomers of caveolin-3 oligomerize to form high molecular mass scaffolding on the cytoplasmic surface of the sarcolemmal membrane. A mutation in one caveolin-3 allele produces an aberrant protein product capable of sequestering the normal caveolin-3 protein in the Golgi apparatus of skeletal muscle cells. Improper caveolin-3 oligomerization and membrane localization result in skeletal muscle T-tubule system derangement, sarcolemmal membrane alterations, and large subsarcolemmal vesicle formation. To date, there have been eight autosomal dominant caveolin-3 mutations identified in the human population. Caveolin-3 mutations can result in four distinct, sometimes overlapping, muscle disease phenotypes: limb girdle muscular dystrophy, rippling muscle disease, distal myopathy, and hyperCKemia. Thus, the caveolin-3 mutant genotype-to-phenotype relation represents a clear example of how genetic background can influence phenotypic outcome. This review examines in detail the reported cases of patients with caveolin-3 mutations and their corresponding muscle disease phenotypes.
4.
Creatine supplementation results in elevated phosphocreatine/adenosine triphosphate (ATP) ratios in the calf muscle of athletes but not in patients with myopathies.
Zange, J, Kornblum, C, Müller, K, Kurtscheid, S, Heck, H, Schröder, R, Grehl, T, Vorgerd, M
Annals of neurology. 2002;(1):126; author reply 126-7