BackgroundInfluenza surveillance data from Africa indicate a substantial disease burden with high mortality. However, local influenza data from district hospitals with limited laboratory facilities are still scarce.ObjectivesTo identify the frequency and seasonal distribution of influenza among hospitalized febrile children in a rural hospital in Ghana and to describe differential diagnoses to other severe febrile infections.MethodsBetween January 2014 and April 2015, all children with a temperature of ≥38°C admitted to a district hospital in Ghana were screened for influenza A and B by RT‐PCR and differentiated to subtypes A(H1N1)pdm09 and A(H3N2). Malaria microscopy and blood cultures were performed for each patient.ResultsA total of 1063 children with a median age of 2 years (IQR: 1‐4 years) were recruited. Of those, 271 (21%) were classified as severe acute respiratory infection (SARI) and 47 (4%) were positive for influenza, namely 26 (55%) influenza B, 15 (32%) A(H1N1)pdm09, and 6 (13%) A(H3N2) cases. Influenza predominantly occurred in children aged 3‐5 years and was more frequently detected in the major rainy season (OR = 2.9; 95% CI: 1.47‐6.19) during the first half of the year. Two (4%) and seven (15%) influenza‐positive children were co‐diagnosed with an invasive bloodstream infection or malaria, respectively.ConclusionInfluenza contributes substantially to the burden of hospitalized febrile children in Ghana being strongly dependent on age and corresponds with the major rainy season during the first half‐year.

Mucolipidosis type II (MLII) is a rare lysosomal storage disorder caused by defective trafficking of lysosomal enzymes. Severe skeletal manifestations are a hallmark of the disease including hip dysplasia. This study aims to describe hip morphology and the natural course of hip pathologies in MLII by systematic evaluation of plain radiographs, ultrasounds and magnetic resonance imaging (MRI). An international two-centered study was performed by retrospective chart review. All MLII patients with at least one pelvic radiograph were included. A total of 16 patients were followed over a mean of 3.5 years (range 0.2-10.7 years). Typical age-dependent radiographic signs identified were femoral cloaking (7/16), rickets/hyperparathyroidism-like changes (6/16) and constrictions of the supra-acetabular part of the os ilium (16/16) and the femoral neck (7/16). The course of acetabular and migration indexes (AI, MI) significantly increased in female patients. However, in the overall group, there was no relevant progression of acetabular dysplasia with a mean AI of 23.0 (range 5 • -41 • ) and 23.7 • (range 5 • -40 • ) at the first and last assessments, respectively. Better knowledge on hip morphology in MLII could lead to earlier diagnosis, improved clinical management and enables assessment of effects of upcoming therapies on the skeletal system.

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Patients with mucopolysaccharidoses (MPS) frequently require anaesthesia for diagnostic or surgical interventions and thereby experience high morbidity. This study aimed to develop a multivariable prediction model for anaesthesia-related complications in MPS. This two-centred study was performed by retrospective chart review of children and adults with MPS undergoing anaesthesia from 2002 until 2018. We retrieved the patients’ demographics, medical history, clinical manifestations, and indication by each anaesthesia. Multivariable mixed-effects logistic regression was calculated for a clinical model based on preoperative predictors preselected by lasso regression and another model based on disease subtypes only. Of the 484 anaesthesia cases in 99 patients, 22.7% experienced at least one adverse event. The clinical model resulted in a better forecast performance than the subtype-model (AICc 460.4 vs. 467.7). The most relevant predictors were hepatosplenomegaly (OR 3.10, CI 1.54–6.26), immobility (OR 3.80, CI 0.98–14.73), and planned major surgery (OR 6.64, CI 2.25–19.55), while disease-specific therapies, i.e., haematopoietic stem cell transplantation (OR 0.45, CI 0.20–1.03), produced a protective effect. Anaesthetic complications can best be predicted by surrogates for advanced disease stages and protective therapeutic factors. Further model validation in different cohorts is needed.

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Purpose Pathogenic variants in GNPTAB and GNPTG, encoding different subunits of GlcNAc-1-phosphotransferase, cause mucolipidosis (ML) II, MLIII alpha/beta, and MLIII gamma. This study aimed to investigate the cellular and molecular bases underlying skeletal abnormalities in patients with MLII and MLIII. Methods We analyzed bone biopsies from patients with MLIII alpha/beta or MLIII gamma by undecalcified histology and histomorphometry. The skeletal status of Gnptgkoand Gnptab-deficient mice was determined and complemented by biochemical analysis of primary Gnptgko bone cells. The clinical relevance of the mouse data was underscored by systematic urinary collagen crosslinks quantification in patients with MLII, MLIII alpha/beta, and MLIII gamma. Results The analysis of iliac crest biopsies revealed that bone remodeling is impaired in patients with GNPTAB-associated MLIII alpha/beta but not with GNPTG-associated MLIII gamma. Opposed to Gnptab-deficient mice, skeletal remodeling is not affected in Gnptgko mice. Most importantly, patients with variants in GNPTAB but not in GNPTG exhibited increased bone resorption. Conclusion The gene-specific impact on bone remodeling in human individuals and in mice proposes distinct molecular functions of the GlcNAc-1-phosphotransferase subunits in bone cells. We therefore appeal for the necessity to classify MLIII based on genetic in addition to clinical criteria to ensure appropriate therapy.

Introduction The pathophysiological significance of the Fabry‐related, non‐classical variant p.D313Y still remains to be solved. This study assesses the involvement of the peripheral nervous system with respect to small fiber neuropathy and neuropathic pain in female patients carrying p.D313Y. Methods This study examined nine females carrying the Fabry‐related p.D313Y variant by obtaining skin punch biopsies above the right lateral malleolus. Intraepidermal nerve fiber density was determined for each patient and compared to reference values matched for the patientʼs decade of life and sex. Moreover, each patient was characterized by a detailed neurological examination and by pain assessment via questionnaire. Results Compared to sex‐matched lower fifth percentile reference values per decade, intraepidermal nerve fiber density was decreased in seven out of nine patients. Four patients reported acral paresthesias and neuropathic pain with an average visual analogue scale score of 7 out of 10 points. Two patients experienced acute pain crises. Six out of seven patients diagnosed with small fiber neuropathy had a their medical history of hypo‐ and/or hyperhidrosis. Discussion The diagnosis of small fiber neuropathy was made in seven out of nine females carrying the non‐classical variant p.D313Y. Moreover, neuropathic pain and symptoms indicative of autonomic nervous system dysfunction seem to be common findings that may be of clinical significance and may warrant therapeutic intervention.