Homozygous missense VPS16 variant is associated with a novel disease, resembling mucopolysaccharidosis-plus syndrome in two siblings.

Disorders of intracellular trafficking are a group of inherited disorders, which often display multisystem phenotypes. Vacuolar protein sorting (VPS) subunit C, composed of VPS11, VPS18, VPS16, and VPS33A proteins, is involved in tethering of endosomes, lysosomes, and autophagosomes. Our group and others have previously described patients with a specific homozygous missense VPS33A variant, exhibiting a storage disease phenotype resembling mucopolysaccharidosis (MPS), termed "MPS-plus syndrome." Here, we report two siblings from a consanguineous Turkish-Arabic family, who have overlapping features of MPS and intracellular trafficking disorders, including short stature, coarse facies, developmental delay, peripheral neuropathy, splenomegaly, spondylar dysplasia, congenital neutropenia, and high-normal glycosaminoglycan excretion. Whole exome sequencing and familial segregation analyses led to the homozygous NM_022575.3:c.540G>T; p.Trp180Cys variant in VPS16 in both siblings. Multiple bioinformatic methods supported the pathogenicity of this variant. Different monoallelic null VPS16 variants and a homozygous missense VPS16 variant had been previously associated with dystonia. A biallelic intronic, probably splice-altering variant in VPS16, causing an MPS-plus syndrome-like disease has been very recently reported in two individuals. The siblings presented herein display no dystonia, but have features of a multisystem storage disorder, representing a novel MPS-plus syndrome-like disease, associated for the first time with VPS16 missense variants.

Secondary hemophagocytic lymphohistiocytosis in pediatric patients: a single center experience and factors that influenced patient prognosis.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome of excessive immune activation. Secondary HLH syndrome develops as a complication of infection, drugs, rheumatologic conditions, or malignancy. The main objectives of this work were to identify the etiology of secondary HLH and prognostic factors associated with mortality. Patients diagnosed with secondary HLH, between January 2011 and December 2016, were retrospectively included in this study. We analyzed clinical and laboratory findings as well as prognostic factors from 24 pediatric patients diagnosed with secondary HLH. The mean age of patients at the time of diagnosis was 79.9 ± 68.7 months (range: 2-202) and 54.2% of the patients were male. The most frequent HLH-2004 criterion was fever (100%). Underlying triggers of HLH were as follows: 13 (54.1%) infections, juvenile idiopathic arthritis in 5 patients (20.8%), drugs in 3 patients (12.5%), malignancies in 2 (0.8%), Kawasaki disease in 1 (0.4%) patient, and 1 (0.4%) with unknown triggers. The median time of diagnosis was 3 days (1-67 days). Overall, the mortality rate was 20.8%. In our logistic regression model, factors associated with mortality were decreased albumin levels (OR1 = 2.3[1.48-3.43]) and etoposide usage (OR2 = 1.22 [1.14-1.89]). The patient's 30-day survival was inferior among patients whose albumin level was 2 g/dL or less compared to those over 2 g/dL. Increased awareness of the underlying condition is critical in HLH patients. Our study emphasizes the prognostic significance of albumin level.

Analysis of Refugee Children Hospitalized in a Tertiary Pediatric Hospital.

Refugee children are defined as an at-risk population as they have a high risk of physical and mental health conditions. While data exist regarding the mental health of refugee children, there are limited data about their medical health issues and mortality. Therefore, this study aimed to analyze the demographic data, clinical results, treatment/management data, and mortality data of hospitalized refugee children. This is a descriptive study that analyzed the demographic data, clinical findings, treatment/management data, and mortality data of 728 refugee children aged between 1 month and 18 years who were hospitalized in a tertiary pediatric hospital between 2013 and 2018. During the 5 year duration of this study (2013-2018), there were 12,031 patients hospitalized in the department of general pediatrics. Of these patients, 728 (6%) were refugee children [median age 1.2 (IQR 4.4) years]. The most frequent ethnic origin was Syrian, followed by Iraqi and Afghan [465 (63.87%); 174 (23.9%), and 39 (5.3%), respectively]. The median duration of hospitalization was 6 (IQR 6) days. Those refugee patients who were hospitalized in the pediatric intensive care unit were significantly younger [median age 3.7 (IQR 9.4) years]. The mortality rate in the department of general pediatrics was 16.4% for refugee patients and 8.6% for non-refugee patients (p = 0.001). A logistic regression model revealed that factors associated with mortality included younger age (OR 1.6; CI 1.2-2.1) and being a refugee (OR 2.1; CI 1.3-3.2). Our study revealed detailed knowledge about demographic, clinical, and mortality data, with the largest known series about refugee children in the literature. The results show that mortality rates are significantly higher in refugee pediatric patients who are hospitalized in Turkey than in non-refugee patients.

Acute haemorrhagic pericarditis: an unusual presentation of Chlamydophila pneumoniae pneumonia infection.

CHLAMYDOPHILA PNEUMONIAE: , a common cause of respiratory tract infections, rarely leads to serious conditions. A 13-year-old boy with serologically confirmed C. pneumoniae infection presented with pneumonia complicated by pericardial and bilateral pleural effusions. He had a large haemorrhagic pericardial effusion from which 1000 ml of fluid was aspirated over 10 days and a right haemorrhagic pleural effusion which required a chest drain and the removal of 700 ml over 5 days. The addition of clarithromycin to ceftriaxone appeared to enhance recovery. As far as we are aware, this is the first report in the English literature of massive haemorrhagic pericardial and pleural effusions in children owing to C. pneumoniae infection.

High Rate of Living Kidney Donation to Immigrant Children Despite Disparities-An Epidemiological Paradox?

Background: Kidney transplantation is the preferred treatment modality for children with end-stage renal disease. In the adult population, migration-related modifiable factors were associated with low living donation rates; no such data are available on the pediatric population. This pilot study therefore compares donation modality, communication, knowledge, and attitudes/beliefs between families of immigrant and non-immigrant descent. Methods: Demographic and clinical characteristics of a cohort of children from 77 families of immigrant (32; 42%) and non-immigrant (45; 58%) descent who had undergone renal transplantation were assessed and related to donation modality at the Medical University of Vienna. In a representative subset, modifiable migration-related factors were assessed in a questionnaire-based study. Results: In immigrant families, information delay, limited communication, low knowledge levels, and self-reported conflicting beliefs were significantly more prevalent than in non-immigrants. The living kidney donation rate to children was high in both populations (immigrants: 63%, non-immigrants: 44%; p = 0.12). Living donation to children on dialysis was even significantly higher in immigrant families (immigrants: 13 out of 20; 57%, non-immigrants: 9 out of 33; 27%; p = 0.03). Conclusion: Contrary to expectations, migration-related disparities did not translate into decreased living donation rates in immigrant families, in particular to children on dialysis. Certain factors might therefore be less important for the living donation process in pediatric care structures and/or might be overcome by yet undefined protective factors. Larger pediatric studies including qualitative and quantitative methods are required to validate and refine current conceptual frameworks integrating the perspective of affected families.

Dynamic Thiol/Disulphide Homeostasis in Children with Nephrotic Syndrome.

BACKGROUND: There is a growing body of evidence showing that there is an association between oxidative damage and kidney injury in patients with nephrotic syndrome (NS). Dynamic thiol/disulphide homeostasis (DTDH) is an important antioxidant system. The aim of this study was to determine if DTDH could be used as a biomarker of antioxidant status in pediatric NS patients using a novel automated method. METHODS: The study included 39 patients with NS and 40 healthy controls. The DTDH level was measured using a calorimetric and automated method developed by Erel and Neselioglu. In the NS group, DTDH was measured during first-attack episode, relapse, and remission. RESULTS: The native thiol, total thiol, and disulphide levels were significantly lower, the native thiol/total thiol ratio was significantly lower, and the disulphide/native thiol and disulphide/total thiol ratios were significantly higher in the NS patients during relapse and first-attack episode than during remission and in the controls. In addition, the native thiol and total thiol levels, and the native thiol/total thiol ratio were significantly lower, and the disulphide/native thiol and disulphide/total thiol ratios were significantly higher in the NS group during remission than those in the control group. CONCLUSIONS: The present findings show that DTDH shifted toward disulphide formation in the NS patients, even during remission. A clearer understanding of the mechanism of this disruption to homeostasis in NS patients might lead to the development of novel therapeutic strategies.

Brucellar terminal ileitis and epididymo-orchitis in an adolescent; case report and review of the literature.

Although brucellosis is a multi-systemic illness, terminal ileitis or colitis due to brucellosis is reported anecdotal in literature. Genitourinary manifestations of Brucella, namely epididymo-orchitis is very rare in childhood brucellosis. Herein, we present a case of brucellosis in a child with a rare combination of terminal ileitis and epididymo-orchitis not reported previously in the literature.