Predominance of null mutations in ataxia-telangiectasia

Ataxia-telangiectasia (A-T) is an autosomal recessive disorder involving cerebellar degeneration, immunodeficiency, chromosomal instability, radiosensitivity and cancer predisposition. The responsible gene, ATM, was recently identified by positional cloning and found to encode a putative 350 kDa protein with a PI 3-kinase-like domain, presumably involved in mediating cell cycle arrest in response to radiation-induced DNA damage. The nature and location of A-T mutations should provide insight into the function of the ATM protein and the molecular basis of this pleiotropic disease. Of 44 A-T mutations identified by us to date, 39 (89%) are expected to inactivate the ATM protein by truncating it, by abolishing correct initiation or termination of translation, or by deleting large segments. Additional mutations are four smaller in-frame deletions and insertions, and one substitution of a highly conserved amino acid at the PI 3-kinase domain. The emerging profile of mutations causing A-T is thus dominated by those expected to completely inactivate the ATM protein. ATM mutations with milder effects may result in phenotypes related, but not identical, to A-T

Clinical heterogeneity can hamper the diagnosis of patients with ZAP70 deficiency

One of the severe combined immunodeficiencies (SCIDs), which is caused by a genetic defect in the signal transduction pathways involved in T-cell activation, is the ZAP70 deficiency. Mutations in ZAP70 lead to both abnormal thymic development and defective T-cell receptor (TCR) signaling of peripheral T-cells. In contrast to the lymphopenia in most SCID patients, ZAP70-deficient patients have lymphocytosis, despite the selective absence of CD8+ T-cells. The clinical presentation is usually before 2 years of age with typical findings of SCID. Here, we present three new ZAP70-deficient patients who vary in their clinical presentation. One of the ZAP70-deficient patients presented as a classical SCID, the second patient presented as a healthy looking wheezy infant, whereas the third patient came to clinical attention for the eczematous skin lesions simulating atopic dermatitis with eosinophilia and elevated immunoglobulin E (IgE), similar to the Omenn syndrome. This study illustrates that awareness of the clinical heterogeneity of ZAP70 deficiency is of utmost importance for making a fast and accurate diagnosis, which will contribute to the improvement of the adequate treatment of this severe immunodeficiency

A view on pediatric airway management: a cross sectional survey study

BACKGROUND: This survey aimed to investigate routine practices and approaches of clinicians on pediatric airway in anesthesia and intensive care medicine. METHODS: A 20-question multiple-choice questionnaire with the possibility to provide open text answers was developed and sent. The survey was sent to the members of European Airway Management Society via a web-based platform. Responses were analyzed thematically. Only the answers from one representative of the pediatric service of each hospital was included into the analysis. RESULTS: Among the members, 143 physicians responded the survey, being anesthesiologists (83.2%), intensivists (11.9%), emergency medicine physicians (2.1%), and (2.8%) pain medicine practitioners. Astraight blade was preferred by 115 participants (80.4%) in newborns, whereas in infants 86 (60.1%) indicated a curved blade and 55 (38.5%) a straight blade. Uncuffed tracheal tube were preferred by 115 participants (80.4%) in newborns, whereas 24 (16.8%) used cuffed tubes. Approximately 2/3 of the participants (89, 62.2%) reported not to use routinely a cuff manometer in their clinical practice, whereas 54 participants (37.8%) use it routinely in pediatric patients. Direct laryngoscopy for routine pediatric tracheal intubation was reported by 127 participants (88.8%), while 16 (11.2%) reported using videolaryngoscopes routinely. Interestingly, 39 (27.3%) had never performed neither videolaryngoscopy nor flexible bronchoscopy in children. These results were significantly less in hospitals with a dedicated pediatric anesthesiologist. CONCLUSIONS: This survey on airway management in pediatric anesthesia revealed that the use of cuffed tubes and the routine monitoring of cuff pressure are rare. In addition, the rate of videolaryngoscopy or flexible optical intubation was low for expected difficult intubation. Our survey highlights the need for properly trained pediatric anesthesiologists working in-line with updated scientific evidence. © 2022 Edizioni Minerva Medica. All rights reserved