Objectives: Posterior reversible encephalopathy syndrome (PRES) is one of the most common neurological complications in hematology-oncology pediatric patients.Despite an increasingly recognized occurrence, no clear consensus exists regarding how best to manage the syndrome, because most cases of PRES have reported in single-case reports or small series. Aim of this paper is to identify incidence, clinical features, management, and outcome of PRES in a large series of hematology-oncology pediatric patients. Methods: The cases of PRES occurred in twelve centers of the Italian Association ofPediatric Hematology and Oncology were reported. Results:One hundred and twenty-four cases of PRES in 112 pediatric patients were recorded with an incidence of 2.1% and 4.7%, respectively, in acute lymphoblastic leukemia in first complete remission and hematopoietic stem cell transplantation (HSCT). The majority of cases occurred after a cycle of chemotherapy rather than after

. The local Ethics Committee approved the protocol. We analyzed data from all the 159 patients admitted in the study period with suspected iron overload based on high TS (above 55% in men and 45% in women) and/or SF (> 322 ng/mL), who had undergone MRI-T2* for heart, liver, spleen, and/or pancreas iron overload and had been screened for the presence of HFE mutations by allele-specific PCR (polymerase chain reaction). The calculations of liver iron concentration (LIC) values were based on liver MRI-T2* measurements, using the Thalassemia-Tools software (Cardiovascular Imaging Solutions, London, UK).Mutations in the HFE gene were identified in 109/159 (68.6%) patients. The most common mutation in our sample was H63D, present in 91 patients (57.2%): 14 (8.8%) were homozygous, 69 (43.4%) heterozygous, and 8 (5%) compound heterozygous for C282Y/H63D. For the C282Y mutation, in contrast, only 5 patients (3.1%) were homozygous and 11 (6.9%) were heterozygous. The S65C mutation was detected in heterozygous state in 2 (2.5%) cases.All 159 patients underwent abdominal MRI-T2* and 126 underwent cardiac MRI-T2* too. Only 3 out of 126 cardiac MRIs had a positive T2* result, mild cardiac overload (T2*: 18.98, 19.14, and 19.8 ms). Of these, two patients had the H63D mutation (1 homozygous and 1 heterozygous) and one patient did not have any of the mutations studied. In the liver, 61 (38.4%) patients had iron overload (T2*: < 11.4 ms and LIC > 2.0 mg/g) of which 57 (35.8%) were light (T2*: 3.83-11.4 ms and LIC: 2.01-6.86 mg/g), and four (2.5%) moderate (T2*: 2.0-3.8 ms and LIC: 7.06-13.56 mg/g). Of these patients with liver overload, 27.9% were C282Y carriers (8.2% homozygous, 11.5% heterozygous, and 8.2% compound heterozygous C282Y/H63D), and 50.8% carried the H63D mutation (14.8% in homozygosis and 36.1% in heterozygosis). Only 12 (19.7%) patients with liver overload did not have the HFE mutation.The presence of C282Y mutation (in either homo or heterozygosis), compound heterozygous (C282/H63D), and H63D in homozygosis was significantly associated with a higher frequency of iron overload in the liver as measured by T2* (P 5 0.001). However, this was not true in patients with H63D in heterozygosis or absence of mutation (P 5 0.42), in which overload frequency was 68.4% and 29.1%, respectively.Pancreatic overload was diagnosed in 33 patients (21%), and 56 patients (35.7%) had splenic overload (Table I). The presence of the C282Y was associated with an overall higher frequency of iron overload. There was also a relatively high frequency (37.3%) of abnormal T2* values in H63D mutants both in the liver and in the spleen, and the frequency of splenic iron overload in H63D mutants was similar to that associated with the C282Y mutation.SF results were available for 152 patients. Median SF was 647 ng/mL (72-13,625), and in 138 patients (90.8%) SF was abnormally high. Overall, in 28 patients (18.2%) serum levels were higher than 1,000 ng/mL, in 80 patients (54%) they varied from 501 to 1,000 ng/mL and in 30 (20.3%) they ranged from 324...

Background-Mutations of UNC13D are causative for familial haemophagocytic lymphohistiocytosis type 3 (FHL3; OMIM 608898).

No abstract

Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated cellular cytotoxicity in humans.