The effect of Melatonin on Improving the benign Prostatic Hyperplasia Urinary Symptoms, a Randomized Clinical Trial.

OBJECTIVE

Malignant hyperthermia (MH) is a classically unapparent pharmacogenetic disorder of the skeletal muscles triggered by inhalational anesthetics or depolarizing muscle relaxants. The disposition to MH is inherited in an autosomal-dominant manner and is primarily due to mutations in the gene for the ryanodine receptor type 1 (RyR1). The present study intended to analyze whether mild muscular symptoms (elevation of the resting CK, cramps in the calves, slight calf hypertrophy) may be associated with susceptibility to MH and/or with histopathological changes.

METHODS

A muscle biopsy was taken from 12 out of 44 blood relatives (three generations) of a large family and was investigated with the halothane/caffeine in vitro contracture test (IVCT). Afterwards a histological, histochemical and immunhistological examination was performed. Altogether in 29 persons the DNA was analyzed for mutations in the RyR1-gene.

RESULTS

Eight persons were diagnosed as susceptible to MH (MHS) by the IVCT, 4 were MH negative. All MHS persons carried the MH causative c.6617C > T (Thr2206Met) mutation and showed slight clinical signs of a myopathy as well as mild biopsy changes with isolated hypotrophic fibers and disseminated small areas with reduction of oxidative staining (multi-minicore like lesions). The Thr2206Met mutation was identified in another further 9 relatives who also experienced mild myopathological features. Clinical MH incidents were not reported in this large family.

CONCLUSION

The RyR1 Thr2206Met mutation is one of the most frequent mutations in the European MH population but carriers are normally healthy. In this study we could demonstrate that the MH causative Thr2206Met mutation may also be associated both with clinical symptoms of a mild myopathy and histopathological changes in the oxidative inter myofibrillar network.