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 within 15 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.

Objective:To determine through the systematic review the survival rate of patients infected by SARS-CoV-2 and previously diagnosed with arterial hypertension and/or diabetesDesign and method:A systematic review of the literature, in eight electronic and bibliographic databases, was conducted from July 8 to 21, 2020. Different combinations of the terms DECS and MESH were used as: (‘SARS-CoV-2’ OR ‘COVID-19’) AND (‘diabetes’ OR ‘arterial hypertension’) AND (‘Survival rate’ OR ‘Prevalence rates’). The selected articles are retrospective, single-center or multi-center, observational cohort studies of patients with COVID-19 disease who had diabetes and/or arterial hypertension. These were subjected to risk of bias assessment, with the help of critical and methodological guidelines (STROBE) and level of evidence (CEBM).Results:326 articles were analyzed by title and type of study, of which 20 were considered relevant. Finally, five retrospective cohort studies that met the inclusion criteria, made in Wuhan, China, were included in this review. All the selected studies affirm that diabetes and hypertension are related to a decrease in the survival rate in patients with COVID-19. Three studies with evidence level 2b and grade of recommendation B, mention factors related to an increase in the survival rate, these are: well-controlled blood glucose, which maintains glycemic variability within 70.26 to 180.16 mg/dL (3.9 to 10.0 mmol/L), patients on pre-admission antihypertensive therapy for SARS-CoV-2 and diabetic patients who do not require insulin may have a lower risk of disease progression and a better prognosis. Additionally, two articles with evidence level 2b and grade of recommendation B, mention the survival rates of 10.6 and 13.9% for diabetics, while 18.8 and 23.4% for hypertensive patients.Conclusions:Based on the evidence included in this review, until now, having comorbidities predisposes patients with COVID-19 to a lower probability of survival. It is recommended to consider that adequate glycemic control and blood pressure are guidelines that benefit the recovery of these patients. However, more studies are needed to identify possible preventive and therapeutic strategies for a more comprehensive management of these patients.