Very few cases of chronic lymphocytic leukemia (CLL) presenting with extreme hyperleukocytosis are reported in the literature. We describe the case of a 66 years old woman, with newly diagnosed CLL presenting with extreme hyperleukocytosis of 774.2 x 109/liter, Rai stage III and Binet stage C. The patient has no comorbidities and the CIRS score (cumulative illness rating scale) is well below 6, with normal creatinine clearance. Some other interesting aspects related with this case are the atypical immunophenotype, the expression of Cyclin D1, and the B hepatitis viral infection, which made her diagnosis and treatment challenging. The patient was tested for NOTCH1 mutation and it was positive. There is important evidence that NOTCH1 mutations are associated with rapidly progressive disease and resistance to treatment. The distinction of CLL from mantle cell lymphoma (MCL) is not always easy because some MCLs may mimic CLL clinically, histologically, and/or phenotypically. The hepatitis B prophylaxis for viral reactivation was not available an in the end the patient was treated only with fludarabine and cyclophosphamide, without rituximab. CD200 should be introduced in the routine panel for flow cytometry to distinguish CLL from mantle cell lymphoma and NOTCH1 mutation is associated with poor prognosis and should be evaluated at diagnosis. CLL with extreme hyperleukocytosis presentation is very rare and sometimes an atypical CLL may represent a diagnostic pitfall.
It is well known that critically ill patients require special attention and additional consideration during their treatment and management. The multiple systems and organ dysfunctions, typical of the critical patient, often results in different patterns of enteral absorption in these patients. Anti-platelet drugs are the cornerstone in treating patients with coronary and cerebrovascular disease. Dual anti-platelet therapy with aspirin and clopidogrel is the treatment of choice in patients undergoing elective percutaneous coronary interventions and is still widely used in patients with acute coronary syndromes. However, despite the use of dual anti-platelet therapy, some patients continue to experience cardiovascular ischemic events. Recurrence of ischemic events is partly attributed to the fact that some patients have poor inhibition of platelet reactivity despite treatment. These patients are considered low- or nonresponders to therapy. The underlying mechanisms leading to resistance are not yet fully elucidated and are probably multifactorial, cellular, genetic and clinical factors being implicated. Several methods have been developed to asses platelet function and can be used to identify patients with persistent platelet reactivity, which have an increased risk of thrombosis. In this paper, the concept of anti-platelet therapy resistance, the underlying mechanisms and the methods used to identify patients with low responsiveness to anti-platelet therapy will be highlighted with a focus on aspirin and clopidogrel therapy and addressing especially critically ill patients.
Molecular genetic testing in craniosynostosis leads to the detection of the mutations in the genes encoding fibroblast growth factor receptors (FGFR), providing information about the etiology of the genetic disorder. Muenke syndrome is produced by p.Pro250Arg mutation in FGFR3 gene with evidence of variable expressivity, representing 8% of the syndromic craniosynostoses.
Here, we present the identification of a p.Pro250Arg pathogenic mutation (c.749C>G) in the FGFR3 gene using Multiplex Ligation-dependent Probes Amplification (MLPA) analysis in conjunction with Sanger sequencing in a patient with craniosynostosis and mild intellectual disability. The MLPA analysis detected a reduced signal of the probe, at the site of the c.749C>G mutation, defined by the presence of one allele of C749>G mutation in the FGFR3 gene, exon 7. Sanger sequencing was performed for confirmation and identified heterozygous p.Pro250Arg pathogenic variant (c.749C>G) in exon 7 of the FGFR3.
In conclusion, we assessed the validity and clinical utility of the combined molecular genetic techniques, MLPA analysis, and Sanger sequencing, for craniosynostosis and intellectual disability, improving not only the diagnostic testing but also the genetic counseling and management of the disorder.
Objectives: The goal of the study was to investigate the correlations between the interleukin-6 IL-6 -174 G/C and IL-6 -572 G/C gene polymorphisms and sepsis risk and severity in adult ICU patients.
Materials and Methods: We prospectively assessed 107 septic patients and divided them into two subgroups: organ dysfunction-free sepsis subgroup S (n=60) and septic shock subgroup SS (n=47). A control group of 96 healthy individuals was included. Both patients and controls underwent IL-6 -174 G/C and -572 G/C genotyping and circulating IL-6 in the study group which were measured from samples taken in the first day of sepsis diagnosis.
Results: No differences in the genotype frequencies of the two polymorphisms between study and control groups were identified. The GC genotype and C allele of IL-6 -572 G/C gene polymorphism was statistically significant more frequent in the organ dysfunction-free subgroup (p=0.01, p=0.004 respectively). No statistically significant differences for the IL-6 -174 G/C gene polymorphism were found between the two sepsis subgroups. Circulating IL-6 levels were significantly higher in the septic shock subgroup and among patients with GG genotypes of both studied polymorphisms.
Conclusion: We underline the possible role of IL-6 -572 G/C as a marker of severe evolution. There is no evidence of a direct role of IL-6 -174 G/C gene polymorphism in sepsis risk and outcome. Il-6 levels are correlated with sepsis severity but not with variant genotype of investigated IL-6 gene polymorphisms.
Background: Conflictual results regarding the relationship between plasmatic level of visfatin and obesity could be explained by the influence of the gene variants involved in the synthesis or action of these hormones.
Objectives: The present study examined the potential implication of single nucleotide polymorphisms (SNPs) of nicotinamide phosphoribosyltransferase (NAMPT) gene that encodes visfatin, in obesity, in a Romanian pediatric population.
Method: A case-control study was conducted on a group of 213 children, divided into two: the case group - 130 overweight and obese children with BMI >1 SD, and the control group - 83 children with normal BMI. The variables analyzed were age, sex, anthropometric parameters, body composition based on bioimpedance analysis, lipid profile, visfatin and insulin plasmatic levels, rs4730153 and rs2302559 visfatin SNPs.
Results: Significant associations were not found between rs4730153 and rs2302559 visfatin SNPs and obesity. Regarding lipid metabolism, there are statistically significant differences between triglyceride levels according to NAMPT rs2302559 genotypes (p=0.045), with heterozygous genotype having the highest level of triglycerides, and also between cholesterol levels according to NAMPT rs4730153 genotypes (p=0.030), with carriers of heterozygote genotype having the highest level of cholesterol. There is a statistically significant difference between the studied parameters in the investigated groups, regarding cholesterol, in carrier of wild-type genotype of NAMPT rs2302559 (p=0.040) and carrier of wild-type genotype of NAMPT rs4730153 (p=0.036). We observed no association of NAMPT rs4730153 and rs2302559 with visfatin levels in the studied groups. Visfatin level was lower in the case group and was correlated with weight (p=0.042), abdominal circumference (p=0.010), waist to height ratio (p=0.040), but not with the elements of the metabolic profile.
Conclusion: NAMPT rs2302559 and rs4730153 polymorphisms do not seem to have a major impact in the development of obesity in children, however there may be an association with lipid profile, but further studies are needed..
Small supernumerary marker chromosome (sSMC) is a rare chromosomal abnormality and is detected in about 0.3% in cases with multiple congenital anomalies (MCA) and/or developmental delay. Different techniques for investigation of cases with MCA and/or developmental delay are available ranging from karyotyping to molecular cytogenetic technique and ultimately multiplex ligation dependent probe amplification (MLPA). Here we present a patient with multiple congenital anomalies for which classical cytogenetic technique was used as a first step in diagnosis and the results being confirmed by MLPA. The karyotype disclosed a sSMC considered to be a fragment of chromosome 22. The MLPA analysis using SALSA MLPA probemix P064-C2 Microdeletion Syndromes-1B confirmed the karyotype results, and according to the manufacturer’s recommendation we performed another confirmation analysis with MLPA probemix P311-B1 Congenital Heart Disease and MLPA probemix P250-B2 DiGeorge. We also suspected an Emanuel syndrome and performed another MLPA analysis with SALSA MLPA probemix P036-E3 Subtelomeres Mix 1 and probemix P070-B3 Subtelomeres Mix 2B for investigation of subtelomeric region that revealed a duplication of 11q25 region and the confirmation was performed using SALSA MLPA probemix P286-B2 Human Telomere-11.
In conclusion, we consider that MLPA is a valuable method for identification of sSMC in children with developmental delay and congenital anomalies. Genetic diagnosis using different molecular techniques, such as MLPA, for increasing accuracy in identification of chromosomal structural aberrations has an important role in clinical diagnosis and in genetic counselling and our case explain the importance of using a specific laboratory technique for each stage of diagnosis.
Background: Pulmonary arterial hypertension (PAH) is an incapacitating disease even in childhood, associated with very poor prognosis. The disease is characterised by endothelial dysfunction. Two of the key endothelial mediators involved in the PAH pathogenesis are nitric oxide (NO) and angiotensinogen (AGT). Purpose of the study: to evaluate the following gene polymorphisms: endothelial nitric oxide synthase (eNOS) G894T, eNOS 4b/4a, and angiotensinogen (AGT) M235T, as well as allele frequency and their association with PAH in children. Material and methods This study included 32 children with pulmonary arterial hypertension secondary to congenital heart disease, 46 children with congenital heart disease without pulmonary arterial hypertension referred to the Pediatric Cardiology Clinic Tg.Mures and 40 healthy controls. All patients underwent a complete physical with NYHA class evaluation, echocardiographic exam and eNOS (G894T, 4b/4a) as well as AGT M235T polymorphisms determination. Results The frequency of eNOS 894T allele (p < 0.0001) was significantly higher in patients with pulmonary arterial hypertension. Conclusions Our results advocate that there is a correlation between eNOS 894T allele and pulmonary arterial hypertension in children