Comments by opponents on the British Medical Association’s guidance on non-therapeutic male circumcision of children seem one-sided and may undermine public health

The British Medical Association(BMA)guidance on non-therapeutic circumcision(NTMC)of male children is limited to ethical,legal and religious issues.Here we evaluate criticisms of the BMA’s guidance by Lempert et al.While their arguments promoting autonomy and consent might be superficially appealing,their claim of high procedural risks and negligible benefits seem one-sided and contrast with high quality evidence of low risk and lifelong benefits.Extensive literature reviews by the American Academy of Pediatrics and the United States Centers for Disease Control and Prevention in developing evidence-based policies,as well as risk-benefit analyses,have found that the medical benefits of infant NTMC greatly exceed the risks,and there is no reduction in sexual function and pleasure.The BMA’s failure to consider the medical benefits of early childhood NTMC may partly explain why this prophylactic intervention is discouraged in the United Kingdom.The consequence is higher prevalence of preventable infections,adverse medical conditions,suffering and net costs to the UK’s National Health Service for treatment of these.Many of the issues and contradictions in the BMA guidance identified by Lempert et al stem from the BMA’s guidance not being sufficiently evidence-based.Indeed,that document called for a review by others of the medical issues surrounding NTMC.While societal factors apply,ultimately,NTMC can only be justified rationally on scientific,evidence-based grounds.Parents are entitled to an accurate presentation of the medical evidence so that they can make an informed decision.Their decision either for or against NTMC should then be respected.

Heart disease in Friedreich's ataxia

Friedreich's ataxia(FRDA), which occurs in 1/50000 live births, is the most prevalent inherited neuromuscular disorder. Nearly all FRDA patients develop cardiomyopathy at some point in their lives. The clinical manifestations of FRDA include ataxia of the limbs and trunk, dysarthria, diabetes mellitus, and cardiac diseases. However, the broad clinical spectrum makes FRDA difficult to identify.The diagnosis of FRDA is based on the presence of suspicious clinical factors, the use of the Harding criteria and, more recently, the use of genetic testing for identifying the expansion of a triplet nucleotide sequence. FRDA is linked to a defect in the mitochondrial protein frataxin; an epigenetic alteration interferes with the folding of this protein, causing a relative deficiency of frataxin in affected patients. Frataxins are small essential proteins whose deficiency causes a range of metabolic disturbances, including oxidative stress, iron-sulfur cluster deficits, and defects in heme synthesis, sulfur amino acid metabolism, energy metabolism, stress responses, and mitochondrial function. The cardiac involvement seen in FRDA is a consequence of mitochondrial proliferation as well as the loss of contractile proteins and the subsequent development of myocardial fibrosis. The walls of the left ventricle become thickened, and different phenotypic manifestations are seen, including concentric or asymmetric hypertrophy and(less commonly) dilated cardiomyopathy. Dilated cardiomyopathy and arrhythmia are associated with mortality in patients with FRDA, whereas hypertrophic cardiomyopathy is not. Systolic function tends to be low-normal in FRDA patients, with an acute decline at the end of life.However, the literature includes only a few long-term prospective studies of cardiac progression in FRDA, and the cause of death is often attributed to heart failure and arrhythmia postmortem. Cardiomyopathy tends to be correlated with the clinical neurologic age of onset and the nucleotide triplet repeat length(i.e.,markers of phenotypic disease severity) rather than the duration of disease or the severity of neurologic symptoms. As most patients are wheelchair-bound within15 years of diagnosis, the clinical determination of cardiac involvement is often complicated by comorbidities. Researchers are currently testing targeted therapies for FRDA, and a centralized database, patient registry, and natural history study have been launched to support these clinical trials. The present review discusses the pathogenesis, clinical manifestations, and spectrum of cardiac disease in FRDA patients and then introduces gene-targeted and pathology-specific therapies as well as screening guidelines that should be used to monitor cardiac disease in this mitochondrial disorder.