Aicardi–Goutières syndrome is an inflammatory disease occurring due to mutations in any of TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, ADAR or IFIH1. We report on 374 patients from 299 families with mutations in these seven genes. Most patients conformed to one of two fairly stereotyped clinical profiles; either exhibiting an in utero disease-onset (74 patients; 22.8% of all patients where data were available), or a post-natal presentation, usually within the first year of life (223 patients; 68.6%), characterized by a sub-acute encephalopathy and a loss of previously acquired skills. Other clinically distinct phenotypes were also observed; particularly, bilateral striatal necrosis (13 patients; 3.6%) and non-syndromic spastic paraparesis (12 patients; 3.4%). We recorded 69 deaths (19.3% of patients with follow-up data). Of 285 patients for whom data were available, 210 (73.7%) were profoundly disabled, with no useful motor, speech and intellectual function. Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, bowel inflammation and systemic lupus erythematosus were seen frequently enough to be confirmed as real associations with the Aicardi-Goutieres syndrome phenotype. We observed a robust relationship between mutations in all seven genes with increased type I interferon activity in cerebrospinal fluid and serum, and the increased expression of interferon-stimulated gene transcripts in peripheral blood. We recorded a positive correlation between the level of cerebrospinal fluid interferon activity assayed within one year of disease presentation and the degree of subsequent disability. Interferon-stimulated gene transcripts remained high in most patients, indicating an ongoing disease process. On the basis of substantial morbidity and mortality, our data highlight the urgent need to define coherent treatment strategies for the phenotypes associated with mutations in the Aicardi–Goutières syndrome-related genes. Our findings also make it clear that a window of therapeutic opportunity exists relevant to the majority of affected patients and indicate that the assessment of type I interferon activity might serve as a useful biomarker in future clinical trials.

Exome sequencing enhances the ability to identify potential nuclear gene mutations in patients with biochemically defined defects affecting multiple mitochondrial respiratory chain complexes. Additional study is required in independent patient populations to determine the utility of this approach in comparison with traditional diagnostic methods.

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The All India Difficult Airway Association (AIDAA) guidelines for management of the unanticipated difficult airway in adults provide a structured, stepwise approach to manage unanticipated difficulty during tracheal intubation in adults. They have been developed based on the available evidence; wherever robust evidence was lacking, or to suit the needs and situation in India, recommendations were arrived at by consensus opinion of airway experts, incorporating the responses to a questionnaire sent to members of the AIDAA and the Indian Society of Anaesthesiologists. We recommend optimum pre-oxygenation and nasal insufflation of 15 L/min oxygen during apnoea in all patients, and calling for help if the initial attempt at intubation is unsuccessful. Transnasal humidified rapid insufflations of oxygen at 70 L/min (transnasal humidified rapid insufflation ventilatory exchange) should be used when available. We recommend no more than three attempts at tracheal intubation and two attempts at supraglottic airway device (SAD) insertion if intubation fails, provided oxygen saturation remains ≥ 95%. Intubation should be confirmed by capnography. Blind tracheal intubation through the SAD is not recommended. If SAD insertion fails, one final attempt at mask ventilation should be tried after ensuring neuromuscular blockade using the optimal technique for mask ventilation. Failure to intubate the trachea as well as an inability to ventilate the lungs by face mask and SAD constitutes ‘complete ventilation failure’, and emergency cricothyroidotomy should be performed. Patient counselling, documentation and standard reporting of the airway difficulty using a ‘difficult airway alert form’ must be done. In addition, the AIDAA provides suggestions for the contents of a difficult airway cart.