ABSTRACT
In preclinical studies growth hormone and its primary mediator IGF-1 have shown potential to increase muscle mass and strength. A single patient with spinal muscular atrophy reported benefit after compassionate use of growth hormone. Therefore we evaluated the efficacy and safety of growth hormone treatment for spinal muscular atrophy in a multicenter, randomised, double-blind, placebo-controlled, crossover pilot trial. Patients (n = 19) with type II/III spinal muscular atrophy were randomised to receive either somatropin (0.03 mg/kg/day) or placebo subcutaneously for 3 months, followed by a 2-month wash-out phase before 3 months of treatment with the contrary remedy. Changes in upper limb muscle strength (megascore for elbow flexion and hand-grip in Newton) were assessed by hand-held myometry as the primary measure of outcome. Secondary outcome measures included lower limb muscle strength, motor function using the Hammersmith Functional Motor Scale and other functional tests for motor function and pulmonary function. Somatropin treatment did not significantly affect upper limb muscle strength (point estimate mean: 0.08 N, 95% confidence interval (CI:-3.79;3.95, p = 0.965), lower limb muscle strength (point estimate mean: 2.23 N, CI:-2.19;6.63, p = 0.302) or muscle and pulmonary function. Side effects occurring during somatropin treatment corresponded with well-known side effects of growth hormone substitution in patients with growth hormone deficiency. In this pilot study, growth hormone treatment did not improve muscle strength or function in patients with spinal muscular atrophy type II/III.
Subject(s)
Hormone Replacement Therapy , Human Growth Hormone/therapeutic use , Spinal Muscular Atrophies of Childhood/drug therapy , Adolescent , Adult , Child , Cross-Over Studies , Disability Evaluation , Double-Blind Method , Female , Hormone Replacement Therapy/adverse effects , Human Growth Hormone/adverse effects , Humans , Lower Extremity/physiopathology , Male , Motor Activity/drug effects , Muscle Strength/drug effects , Pilot Projects , Respiratory Function Tests , Spinal Muscular Atrophies of Childhood/physiopathology , Treatment Outcome , Upper Extremity/physiopathology , Young AdultABSTRACT
The identification of an ever increasing number of gene defects in patients with neuromuscular disorders has disclosed both marked phenotype and genotype variability and considerable disease overlap. In order to offer an economic strategy to characterise the molecular defect in patients with unclassified neuromuscular disorders, we designed DNA marker sets for linkage analysis of 62 distinct neuromuscular disorders gene loci, including all known muscular dystrophies, congenital myopathies, congenital myasthenic syndromes and myotonias. Genotyping of marker loci of 140 clinically well-characterised families with unclassified neuromuscular disorders reduced the number of candidates to one or two genes in 49 % of the families. Subsequent mutation analysis and genome-wide scans enabled the determination of the genetic defect in 31 % of the families including the identification of a new gene and a new mutation in an unexpected candidate gene. This highlights the effective application of this approach both for diagnostic strategies as well as for the identification of new loci and genes.
Subject(s)
Genetic Heterogeneity , Molecular Diagnostic Techniques/methods , Muscle Proteins/genetics , Neuromuscular Diseases/diagnosis , Neuromuscular Diseases/genetics , DNA Mutational Analysis/methods , Databases, Genetic/statistics & numerical data , Diagnosis, Differential , Family Health , Genotype , Humans , Molecular Diagnostic Techniques/economics , Neuromuscular Diseases/classificationABSTRACT
In recent years potassium bromide has again been used with increasing frequency in the treatment of epilepsy. A 3-year-old girl with bromoderma tuberosum following such treatment is described; the symptoms disappeared after reduction of the bromide dose.
