BackgroundHemophagocytic lymphohistiocytosis (HLH) is a rapid-onset, potentially fatal hyperinflammatory syndrome. A prompt molecular diagnosis is crucial for appropriate clinical management. Here, we validated and prospectively evaluated a targeted high-throughput sequencing approach for HLH diagnostics.MethodsA high-throughput sequencing strategy of 12 genes linked to HLH was validated in 13 patients with previously identified HLH-associated mutations and prospectively evaluated in 58 HLH patients. Moreover, 2504 healthy individuals from the 1000 Genomes project were analyzed in silico for variants in the same genes.ResultsAnalyses revealed a mutation detection sensitivity of 97.3 %, an average coverage per gene of 98.0 %, and adequate coverage over 98.6 % of sites previously reported as mutated in these genes. In the prospective cohort, we achieved a diagnosis in 22 out of 58 patients (38 %). Genetically undiagnosed HLH patients had a later age at onset and manifested higher frequencies of known secondary HLH triggers. Rare, putatively pathogenic monoallelic variants were identified in nine patients. However, such monoallelic variants were not enriched compared with healthy individuals.ConclusionsWe have established a comprehensive high-throughput platform for genetic screening of patients with HLH. Almost all cases with reduced natural killer cell function received a diagnosis, but the majority of the prospective cases remain genetically unexplained, highlighting genetic heterogeneity and environmental impact within HLH. Moreover, in silico analyses of the genetic variation affecting HLH-related genes in the general population suggest caution with respect to interpreting causality between monoallelic mutations and HLH. A complete understanding of the genetic susceptibility to HLH thus requires further in-depth investigations, including genome sequencing and detailed immunological characterization.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-015-0244-1) contains supplementary material, which is available to authorized users.

Megaloblastic anaemia due to vitamin B12 deficiency is rare in childhood. However, as most cases are due to maternal insufficiency, it is mainly seen in breastfed infants especially when the mother's socioeconomic status is low and the nutrition is not adequate. We present case of two Syrian refugee infants with severe vitamin B12 deficiency with pancytopenia, hepatosplenomegaly and leukoerythroblastosis.

The diagnosis of mild bleeding disorders is not easy as most of the "healthy" individuals also report bleeding symptoms. In order to get a precise bleeding history, Pediatric Bleeding Questionnaire (PBQ) has been developed. In our study, Turkish children diagnosed with Von Willebrand disease (VWD), platelet function defect (PFD), and healthy children without any symptoms (control group 1) and healthy children with symptoms but found hemostatically normal (control group 2) were analyzed with PBQ. The cut off level for "positive bleeding score" was found to be ≥2 (area under the curve [AUC]: 0.785, 95% confidence interval [CI]: 0.718-0.852). The sensitivity, specificity, positive predictive value, and negative predictive value of PBQ to define VWD versus control group 1 was 100%, 97.4%, 96.4%, and 100%; VWD versus control group 2 was 100%, 53.1%, 64.3%, and 100%; PFD versus control group 1 was 93.3%, 53.1%, 73.7%, and 85%; and PFD versus control group 2 was 93.3%, 53.1%, 73.7%, and 85%, respectively.

Infantile haemangiomas, benign vascular tumours seen in 4-10% of infants are characterised by their spontaneous remission following a 3-9 month period of dynamic growth. Propranolol has been reported to be used as a successful treatment of severe symptomatic infantile haemangiomas. Hyperkalaemia has not been recognised as a serious effect of propranolol since recently. Here, we would like to portray a 2-year-old male patient with intestinal haemangiomatosis who presented with severe hyperkalaemia and was successfully managed with hydration, loop diuretics, potassium binding granules, inhaler β-2 agonists and insulin. To date, this is the first case of intestinal haemangiomatosis complicated with severe hyperkalaemia. Our case suggested the idea of close monitorisation of potassium levels as well as haemodynamic status at the initialisation of the propranolol treatment.

Little is known about the likelihood of curing children with high-dose chemotherapy regimens for treatment of childhood acute lymphoblastic leukemia (ALL) in Turkey. The authors here report their 13 years' experience with original ALL-BFM (Berlin-Franfurt-Münster) 95 protocol in a cohort of 140 Turkish children with ALL. Complete remission rate was 97.7% with a relapse rate of 12.9% and death rate 17.9% during a median follow-up of 69 months. The event-free survival (EFS), disease-free survival (DFS), and overall survival (OS) in these patients at 12 years were 75.0%, 87.1%, and 80.6%, respectively. These results show that ALL-BFM 95 protocol is equally applicable in the experienced centers, even in developing countries without substantial treatment-related toxicity. High rate of infection deaths are to be reduced with correct policies.