Leri-Weill Dyschondrosteosis Caused by a Leaky Homozygous SHOX Splice-Site Variant.

SHOX deficiency is a common genetic cause of short stature of variable degree. SHOX haploinsufficiency causes Leri-Weill dyschondrosteosis (LWD) as well as nonspecific short stature. SHOX haploinsufficiency is known to result from heterozygous loss-of-function variants with pseudo-autosomal dominant inheritance, while biallelic SHOX loss-of-function variants cause the more severe skeletal dysplasia, Langer mesomelic dyschondrosteosis (LMD). Here we report for the first time the pseudo-autosomal recessive inheritance of LWD in two siblings caused by a novel homozygous non-canonical, leaky splice-site variant in intron 3 of SHOX: c.544+5G>C. Transcript analyses in patient-derived fibroblasts showed homozygous patients to produce approximately equal amounts of normally spliced mRNA and mRNA with the abnormal retention of intron 3 and containing a premature stop codon (p.Val183Glyfs*31). The aberrant transcript was shown to undergo nonsense-mediated mRNA decay, and thus resulting in SHOX haploinsufficiency in the homozygous patient. Six healthy relatives who are of normal height are heterozygous for this variant and fibroblasts from a heterozygote for the c.544+5G>C variant produced wild-type transcript amounts comparable to healthy control. The unique situation reported here highlights the fact that the dosage of SHOX determines the clinical phenotype rather than the Mendelian inheritance pattern of SHOX variants. This study extends the molecular and inheritance spectrum of SHOX deficiency disorder and highlights the importance of functional testing of SHOX variants of unknown significance in order to allow appropriate counseling and precision medicine for each family individual.

Streptococcus pneumoniae colonization in health care professionals at a tertiary university pediatric hospital.

Streptococcus pneumoniae is a commensal of the human upper respiratory tract. In certain cases, it can lead to serious invasive infections peaking in very young children and the elderly. Especially young children are frequent carriers and are thus regarded as the reservoir for horizontal transmission of pneumococci. This is the first study evaluating pneumococcal colonization patterns in healthcare professionals working in a tertiary care pediatric hospital, including carriage prevalence, serotype distribution, and risk factors for carriage. One oropharyngeal and one nasal swab per individual were directly plated onto appropriate agar plates and conventional culture was used for bacterial identification. Pneumococcal isolates underwent serotyping using Neufeld's Quellung reaction with type-specific antisera. Additional nasal and oropharyngeal swabs were taken for qPCR analysis targeting lytA. In total, 437 individuals were enrolled. S. pneumoniae was isolated in 4.8% (21/437) of the study cohort using conventional culture and in 20.1% (88/437) of subjects using qPCR. Independent risk factors for pneumococcal carriage were living in the same household with children under 8 years of age and being aged 36-45 years with a carriage prevalence reaching 11.6% (vs. 2.9%, p = 0.002) and 6.7% (vs. 4.3%, p = 0.029), respectively. The most common serotypes were 6C and 3. A total of 71.4% (15/21) of the detected serotypes are not included in any currently available pneumococcal vaccine; 28.6% (6/21) of the carried serotypes are included in the PCV13 vaccine. We found a relevant amount of pneumococcal carriage bearing the potential risk of horizontal in-hospital transmission.

Hemadsorption as rescue therapy for patients with multisystem organ failure in pediatric intensive care-Report of two cases reports and review of the literature.

Hemadsorption via the cytokine-adsorber CytoSorb (CytoSorbents Europe, Berlin, Germany) has successfully been used as an adjunctive method in adults, mainly for the purpose of immunomodulation under acute inflammatory conditions such as sepsis and cardiac surgery. In recent years, there has been growing interest in its use in pediatric intensive care to improve outcomes in patients with multiple organ failure following an inflammatory illness. Literature on the application of CytoSorb in neonatal and pediatric patients is scarce, though the implication is that it could be an effective last-resort treatment option in critically ill pediatric patients. Herein we present the clinical cases of two pediatric patients successfully treated with a combination of the CytoSorb hemadsorber, continuous renal replacement therapy, and extracorporeal membrane oxygenation due to multiple organ failure following different underlying medical conditions. Patient 1 was a 7-month-old male child with Down's syndrome admitted to the Pediatric Intensive Care Unit (PICU) after congenital heart surgery, who developed antimicrobial-resistant septic shock and severe acute respiratory distress syndrome. Patient 2 was a 2-year-old male child admitted to the PICU with influenza A-associated acute liver failure resulting in hyperammonemia, lactate acidosis, hemodynamic instability, and acute kidney failure. In both patients, hemadsorption with CytoSorb was initiated as an adjunctive rescue therapy to treat refractory multisystem organ failure. Improvement of laboratory and clinical parameters was observed within hours of treatment initiation. The application of the hemadsorber-developed for use in adults-proved simple and safe for use in both of our low-weight pediatric patients.

Pharyngeal carriage rates of Neisseria meningitidis in health care professionals at a tertiary university pediatric hospital.

Pharyngeal carriage is the reservoir for Neisseria meningitidis in the population and the first step in disease transmission. Especially in young infants and adolescents, N. meningitidis can cause serious invasive infection with high fatality rates and high rates of long-term sequelae among survivors. The aim of this study was to determine N. meningitidis colonization rates in asymptomatic health care professionals at a tertiary university pediatric hospital and to identify risk factors for carriage. This cross-sectional meningococcal carriage survey was conducted between April and October 2018 at the Medical University of Vienna. Individuals working as nurses, pediatricians, or medical students were enrolled. Oropharyngeal swabs were directly plated onto selective agar plates and conventional culture was used for bacterial identification. Meningococcal isolates were further characterized using whole-genome sequencing. A total of 437 oropharyngeal specimens were collected. Overall, meningococcal carriage prevalence was 1.14% (5/437), with 0.7% (3/437) for capsular genotype B, and 0.5% (2/437) for capsular genotype W. Mean age of carriers was significantly lower than of non-carriers (24.2 vs. 35.8; p = 0.004). The highest carriage rate of 4.4% (4/91) was found in the age group 18-25. Carriage was negatively associated with age and timespan working in pediatrics. This is the first study evaluating the prevalence of Neisseria meningitidis carriage in health care professionals working in Pediatrics and Adolescent Medicine. Carriage was in general lower than expected for all age groups, implicating a low risk of meningococcal transmission via this population.