Targeted high-throughput sequencing for genetic diagnostics of hemophagocytic lymphohistiocytosis

Background: Hemophagocytic 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. Methods: A 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. Results: Analyses 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. Conclusions: We 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.Peer reviewe

Management of peripheral facial nerve palsy

Peripheral facial nerve palsy (FNP) may (secondary FNP) or may not have a detectable cause (Bell’s palsy). Three quarters of peripheral FNP are primary and one quarter secondary. The most prevalent causes of secondary FNP are systemic viral infections, trauma, surgery, diabetes, local infections, tumor, immunological disorders, or drugs. The diagnosis of FNP relies upon the presence of typical symptoms and signs, blood chemical investigations, cerebro-spinal-fluid-investigations, X-ray of the scull and mastoid, cerebral MRI, or nerve conduction studies. Bell’s palsy may be diagnosed after exclusion of all secondary causes, but causes of secondary FNP and Bell’s palsy may coexist. Treatment of secondary FNP is based on the therapy of the underlying disorder. Treatment of Bell’s palsy is controversial due to the lack of large, randomized, controlled, prospective studies. There are indications that steroids or antiviral agents are beneficial but also studies, which show no beneficial effect. Additional measures include eye protection, physiotherapy, acupuncture, botulinum toxin, or possibly surgery. Prognosis of Bell’s palsy is fair with complete recovery in about 80% of the cases, 15% experience some kind of permanent nerve damage and 5% remain with severe sequelae

Turkish pup registry and national data for inhibitor rates; rodin and sippet effects on hemophilia care

WOS: 000423774100167PfizerPfizer; BayerBayer AG; Shire; Novo NordiskNovo NordiskK. Kavakli Grant/Research support from: Pfizer, Bayer, Shire, Novo Nordisk, Consultant for: Novo Nordisk, Bayer, Shire, Pfizer, LFB, Speaker Bureau of: Novo Nordisk, Shire, Bayer, Pfizer, A. Unuvar: None declared, C. Balkan Consultant for: Novo Nordisk, Bayer, Shire, Pfizer, Speaker Bureau of: Novo Nordisk, Bayer, Shire, Pfizer

Parvovirus B19 in the acute arthropathies and juvenile rheumatoid arthritis

Objective: To evaluate the prevalence of recent parvovirus B19 infection in a cohort of children presenting with acute arthropathy and to determine the prevalence of a subsequent diagnosis of juvenile rheumatoid arthritis in this cohort

A rare case of unilateral linear lichen planus pigmentosus

Lichen planus pigmentosus (LPP) is a rare clinical variant of the lichen planus. It presents with pigmented, dark brown macular lesions on the flexural or sun exposed regions. Linear LPP is presented with hyperpigmented lesions along the lines of Blaschko. To the best of our knowledge, there are a few cases of linear LPP which have been reported in the literature. In our case report, we present a female Turkish patient with unilateral linear LPP that manifested as asymptomatic brown macular lesions, distributed along the lines of Blaschko between the middle part of the left gluteal region and the left calf

Age-specific seroepidemiology of hepatitis A, B, and E infections among children in Istanbul, Turkey

This study was performed for evaluation of seroprevalence of hepatitis A, B, and E among children in Istanbul, Turkey. The study group included 909 children who were 6 months-15 years of age. The children were separated to three age groups: Group 1 (6 months-4.9 years; n = 321), Group 2 (5.0-9.9 years; n = 318), and Group 3 (10.0-15.0 years; n = 270). Group 1 was divided to two subgroups for evaluation of the maternal antibody sera (6 months-2 years and over 2 years). Serum IgG anti-HAV, anti-HBc, and anti-HEV were tested by commercial ELISA kits. The data were studied by multivariant analysis. In all subjects, seroprevalence of hepatitis A, B, and E were determined as 29, 15.9, and 2.1% respectively. The prevalence of hepatitis A increased with age (p 0.05). The seroprevalence of hepatitis E virus infection was higher in Group 1 (3.7%) than Group 3 (0.3%; p < 0.05). In Group 1 first subgroup, between 6 month and 2 year, antibody levels were 12.2, 17.3, and 4.8% respectively, for anti-HAV IgG, anti-HBc IgG and anti-HEV IgG. Hepatitis A and B infection is a community health problem, but hepatitis E infection is low in children in Istanbul, Turkey. The high positive rate in Group 1 for IgG anti-HEV may be due to maternal antibodies