Defects in lipid homeostasis reflect the function of TANGO2 in phospholipid and neutral lipid metabolism.

We show that TANGO2 in mammalian cells localizes predominantly to mitochondria and partially at mitochondria sites juxtaposed to lipid droplets (LDs) and the endoplasmic reticulum. HepG2 cells and fibroblasts of patients lacking TANGO2 exhibit enlarged LDs. Quantitative lipidomics revealed a marked increase in lysophosphatidic acid (LPA) and a concomitant decrease in its biosynthetic precursor phosphatidic acid (PA). These changes were exacerbated in nutrient-starved cells. Based on our data, we suggest that TANGO2 function is linked to acyl-CoA metabolism, which is necessary for the acylation of LPA to generate PA. The defect in acyl-CoA availability impacts the metabolism of many other fatty acids, generates high levels of reactive oxygen species, and promotes lipid peroxidation. We suggest that the increased size of LDs is a combination of enrichment in peroxidized lipids and a defect in their catabolism. Our findings help explain the physiological consequence of mutations in TANGO2 that induce acute metabolic crises, including rhabdomyolysis, cardiomyopathy, and cardiac arrhythmias, often leading to fatality upon starvation and stress.

Clinical Practice Guideline recommendations on examination of the upper airway for adults with suspected obstructive sleep apnoea-hypopnoea syndrome. / Recomendaciones de la Guía de Práctica Clínica de la exploración de la vía aérea superior para pacientes adultos con sospecha de síndrome de apnea-hipoapnea obstructiva del sueño (versión reducida).

In November 2014 the Spanish Society of Otolaryngology, the Spanish Sleep Society and the Spanish Society of Maxillofacial Surgery proposed and endorsed the development of a Clinical Practice Guideline on the physical examination of the upper airway in patients with obstructive sleep apnoea. The Guideline strictly followed the recommendations of the manual for the preparation of clinical practice guidelines of the National Health System 2007 and 2009 and the manual of the Scottish Intercollegiate Guidelines Network (SIGN) 2015. The final document could be highly useful for the purposes that were originally proposed: to act as a reference to unify the regions that should be explored in patients with obstructive sleep apnoea-hypopnoea syndrome, the type of examination and how to grade it, and specific to all the care areas to which these patients have access. The conclusions and recommendations are based on a thorough and up-to-date review of the literature with a high level of evidence, as well as the experience and knowledge demonstrated by all the members of the drafting group. This group was formed bearing in mind at all times the transversality of the project, and, therefore, specialists from all the involved areas participated (maxillofacial surgery, family medicine, pneumology, clinical neurophysiology, odontology and otolaryngology). The external reviewers of the final text were selected along the same lines.