IVS-II-16 (G>C) (HBB: c.315+16G>C) or IVS-II-666 (C>T) (HBB: c.316-185C>T) Mutations Trigger an Hb S (HBB: c.20A>T)/ß+-Thalassemia Phenotype in an Hb S Trait Patient.

Sickle cell trait is a medical condition caused by the presence of both mutant Hb S (HBB: c.20A>T) and normal Hb A alleles. Although sickle cell trait is typically considered to be asymptomatic and benign, genetic modifiers and mutations can lead to severe clinical complications. In this study, the possible pathogenicity of the IVS-II-16 (G>C) (HBB: c.315+16G>C) and IVS-II-666 (C>T) (HBB: c.316-185C>T) mutations, which are considered to be neutral polymorphisms, and the association between the Hb S mutation are presented. To the best of our knowledge, these polymorphisms have not been previously reported in any sickle cell trait patient, and no relevant studies have been conducted. We recently studied a 40-year-old woman (proband), diagnosed to be an Hb S/ß-thalassemia (ß-thal) carrier. ß-Globin mutations were analyzed using a DNA sequencer based on the Sanger method. The HbVar and ClinVar databases show IVS-II-16 and IVS-II-666 to be intronic mutations. However, statements in these data banks contradict our findings. In the present study, a transfusion-dependent Hb S patient, behaving as an Hb S/ß-thal case due to these mutations, was reported. These mutations have not been previously reported in an Hb S patient. Although the IVS-II-16 and IVS-II-666 mutations were previously reported as benign, they converted the Hb S phenotype to transfusion-dependent Hb S/ß-thal when combined with Hb S. In this regard, IVS-II-16 and IVS-II-666 mutations may not be innocent, as previously thought.

Secondary antifungal prophylaxis in pediatric hematopoietic stem cell transplants.

Invasive fungal infections (IFIs) constitute a leading cause of morbidity and infection-related mortality among hematopoietic stem cell transplant (HSCT) recipients. With the use of secondary prophylaxis, a history of IFI is not an absolute contraindication to allo-HSCT. However, still, IFI recurrence remains a risk factor for transplant-related mortality. In this study, of the 105 children undergoing HSCT between April 2010 and February 2013, 10 patients who had IFI history before transplantation and had undergone allo-HSCT were evaluated retrospectively to investigate results of secondary prophylaxis. In conclusion, our study shows that amphotericin B and caspofungin was successful as secondary antifungal prophylaxis agents with no relapse of IFI. In addition, after engraftment, secondary prophylaxis was continued with voriconazole orally in 4 patients that yielded good results.

Defective UNC13D gene-associated familial hemophagocytic lymphohistiocytosis triggered by visceral leishmaniasis: a diagnostic challenge.

BACKGROUND: Visceral leishmaniasis (VL) triggered genetic hemophagocytic lymphohistiocytosis (HLH) is clinically challenging. OBSERVATIONS: One-year-old VL-HLH patient improved after liposomal-amphotericin-B therapy, but subsequently deteriorated, although bone marrow amastigotes disappeared. Symptoms resolved after 8 weeks of HLH-2004 therapy but recurred upon cessation. Homozygous UNC13D gene 627delT mutation was identified however stem cell donor was unavailable. The patient died at age 4 years after central nervous system attacks and HLH recurrences. CONCLUSIONS: VL in HLH patients does not exclude a genetic etiology and requires structured clinical management. VL should be excluded in all HLH patients in endemic regions before immunochemotherapy, which is recommended for VL-HLH patients unresponsive to VL treatment and/or reactivated.

Ferritin and hyperactivity ratings in attention deficit hyperactivity disorder.

BACKGROUND: Iron is a co-factor of tyrosine hydroxylase which is a critical enzyme in dopamine synthesis. Dopamine has been implicated in the pathophysiology of attention deficit hyperactivity disorder (ADHD). Our objective was to investigate the association of ferritin level with parent and teacher ratings and cognitive measures after controlling for age, sex, ADHD subtype, comorbid conditions, hemoglobin, mean corpuscular volume and reticulocyte distribution width in a large sample. METHODS: The study included 713 children and adolescents with ADHD (613 boys; age 7-15 years). Conners' Parent Rating Scale (CPRS) and Conners' Teacher Rating Scale (CTRS) were obtained. In a subgroup of patients we conducted Digit Span, Digit Symbol, Trail-making Tests as measures of attention and executive functioning. RESULTS: Multiple regression analysis indicated that CPRS Hyperactivity score was significantly associated with ferritin level (B =-0.12; t =-3.1; P < 0.01). Other CPRS and CTRS scores as well as cognitive measures were not associated with ferritin level. CONCLUSIONS: Although it is not possible to make an inference on causality in cross-sectional studies, the results of this largest-scale cross-sectional field study to date suggest that lower ferritin level might be associated with parent-reported hyperactivity after controlling for important confounding factors.