Increased referrals for congenital hyperinsulinism genetic testing in children with trisomy 21 reflects the high burden of non-genetic risk factors in this group.

BACKGROUND: Hyperinsulinism results from inappropriate insulin secretion during hypoglycaemia. Down syndrome is causally linked to a number of endocrine disorders including Type 1 diabetes and neonatal diabetes. We noted a high number of individuals with Down syndrome referred for hyperinsulinism genetic testing, and therefore aimed to investigate whether the prevalence of Down syndrome was increased in our hyperinsulinism cohort compared to the population. METHODS: We identified individuals with Down syndrome referred for hyperinsulinism genetic testing to the Exeter Genomics Laboratory between 2008 and 2020. We sequenced the known hyperinsulinism genes in all individuals and investigated their clinical features. RESULTS: We identified 11 individuals with Down syndrome in a cohort of 2011 patients referred for genetic testing for hyperinsulinism. This represents an increased prevalence compared to the population (2.5/2011 expected vs. 11/2011 observed, p = 6.8 × 10-5 ). A pathogenic ABCC8 mutation was identified in one of the 11 individuals. Of the remaining 10 individuals, five had non-genetic risk factors for hyperinsulinism resulting from the Down syndrome phenotype: intrauterine growth restriction, prematurity, gastric/oesophageal surgery, and asparaginase treatment for leukaemia. For five individuals no risk factors for hypoglycaemia were reported although two of these individuals had transient hyperinsulinism and one was lost to follow-up. CONCLUSIONS: Down syndrome is more common in patients with hyperinsulinism than in the population. This is likely due to an increased burden of non-genetic risk factors resulting from the Down syndrome phenotype. Down syndrome should not preclude genetic testing as coincidental monogenic hyperinsulinism and Down syndrome is possible.

Respiratory syncytial virus binds and undergoes transcription in neutrophils from the blood and airways of infants with severe bronchiolitis.

BACKGROUND: Neutrophils are the predominant cell in the lung inflammatory infiltrate of infants with respiratory syncytial virus (RSV) bronchiolitis. Although it has previously been shown that neutrophils from both blood and bronchoalveolar lavage (BAL) are activated, little is understood about their role in response to RSV infection. This study investigated whether RSV proteins and mRNA are present in neutrophils from blood and BAL of infected infants. METHODS: We obtained blood and BAL samples from 20 infants with severe RSV bronchiolitis and 8 healthy control infants. Neutrophil RSV F, G, and N proteins, RSV N genomic RNA, and messenger RNA (mRNA) were quantified. RESULTS: RSV proteins were found in BAL and blood neutrophils in infants with RSV disease but not in neutrophils from healthy infants. BAL and blood neutrophils from infants with RSV disease, but not those from healthy infants, expressed RSV N genomic RNA, indicating uptake of whole virus; 17 of 20 BAL and 8 of 9 blood neutrophils from patients expressed RSV N mRNA. CONCLUSIONS: This work shows, for the first time, the presence of RSV proteins and mRNA transcripts within BAL and blood neutrophils from infants with severe RSV bronchiolitis.

Self-assessment of acute mountain sickness in adolescents: a pilot study.

OBJECTIVE: To perform a pilot study exploring the prevalence of acute mountain sickness (AMS) in adolescents on ascent to altitude and evaluating whether this age group is capable of self-assessment of AMS using the Lake Louise scoring system. METHODS: Twelve teenagers aged 15 to 18 years old (5 girls) traveled for 21 days between 2400 and 5500 m. Each member of the expedition completed a Lake Louise self-assessment questionnaire on a daily basis. Group leaders (nonmedical) were informed about any subject with a score of 3 or more. Appropriate treatments were then initiated. Detailed analysis of data was undertaken on return to the UK. RESULTS: There was 100% completion of 252 questionnaires. Eleven of the 12 subjects (91.7%) had symptom scores greater than or equal to 3, consistent with a diagnosis of AMS, on at least one day (range, 0-8). Symptoms of AMS were more common in the female group members (P = .041). CONCLUSIONS: AMS is a common problem among adolescents. There are increasing numbers of adolescents traveling to high altitudes, and there appears to be a lack of information about the prevalence of AMS in this age group. Motivated adolescents seemed capable of self-monitoring for AMS using the Lake Louise questionnaire. Combined with an appropriate ascent profile and support, we feel this approach may contribute to safety in the mountains and merits further study.