Abstract
Objectives
Hemoglobin disorders are quite heterogeneous in the Turkish population. Up to now, more than forty different beta thalassemia mutations and 60 hemoglobin variants have been ...characterized in the country. The aim of this study was to investigate genetic heterogeneity of HBB gene mutations in patients and their parents at Southeastern Anatolia in Turkey.
Methods
Genomic DNA was isolated from 145 thalassemic patients’ blood samples and their parents in this study. Ten different HBB gene mutations HBB:c.-80T>A, HBB:c.17_18delCT, HBB:c.25_26delAA, HBB:c.92+1G>A, HBB:c.92+5G>C, HBB:c.92+6T>C, HBB:c.93-21G>A, HBB:c.135delC, HBB:c.315+1G>A, HBB:c.316-106C>G were screened by amplification refractory mutation system. Four Hb variants and some rare beta thalassemia mutation were characterized by DNA sequencing.
Results
In this study, 97 homozygous and 48 compound heterozygous thalassemic patients were diagnosed by molecular genetic analyses. As a results, 18 β-thalassemia mutations and four abnormal hemoglobins; HBB:c.20A>T, HBB:c.364G>C, HBB:c.34G>A and HBB:c.208G>A were detected at Dicle University Hospital.
Conclusions
In the results, HBB:c.93-21G>A is the most common mutation in the region. Three mutations (HBB:c.93-21G>A), (HBB:c.25_26delAA) and (HBB:c.135delC) account for about 58 per cent of all the point mutations. Except HBB:c.20A>T and HBB:c.364G>C, two silent Hb variants (HBB:c.34G>A and HBB:c.208G>A) were detected in this study. Hb Hamilton β11 (GTT>ATT) Val>Ile was seen first time in Turkey.
The aim of this study is to examine the thickness of choroidal, macular and peripapillary retinal nerve fiber layer by spectral-domain optical coherence tomography (SD-OCT) in pediatric patients with ...sickle cell anemia (SCA) without retinopathy.
A total of 75 children (30 SCA patients (Group 1) and 45 healthy individuals (Group 2) were included in the study. Macular (central, superior, inferior, nasal, temporal), choroidal (subfoveal, at nasal distances from the central fovea of 1000 μm N1, 2000 μm N2, 3000 μm N3, at temporal distances from the central fovea of 1000 μm T1, 2000 μm T2, 3000 μm T3) and RNFL (average, temporal, superotemporal, inferotemporal, nasal, inferonasal and superonasal) measurements were performed by SD-OCT. These parameters were compared with healthy children with similar demographic characteristics.
The mean age was 14.11±3.86 (11-18) in sickle cell anemia patients and 13.15± 2.69 (10-18) in the healthy control group. Of the patients, 56.6% (n=17) of Group 1 and 44.4% (n=20) of Group 2 were male. Choroidal measurements made in the subfoveal, N1, N2, N3, T1, T2 and T3 quadrants showed that the choroid was thinner in 6 quadrants in SCA patients compared to the healthy group (p = 0.003, p = 0.039, p = 0.035, p = 0.595, p = 0.006, p = 0.005, p = 0.047, respectively). In RNFL measurements, there was significant thinning in the temporal, inferotemporal, and nasal quadrants of SCA patients compared to the healthy group. Changes in other quadrants were not significant.
SD-OCT is a useful imaging method in the diagnosis and screening in patients with SCA without retinopathy. Early diagnosis of retinopathy during subclinical disease will prevent visual loss in these patients.
Splenic iron overload is the most common clinical condition in patients with thalassemia. However, few studies of the effects of splenectomy have been published.
To evaluate the relationship between ...splenic iron overload and liver, heart and muscle features visible in T2*-weighted magnetic resonance imaging, and to investigate the effects of splenectomy on these tissues in patients with beta-thalassemia major (TM).
We retrospectively included 131 patients (76 male and 55 female) diagnosed with TM. All radiological assessments were performed with the aid of a Philips Achieva 1.5T scanner running a multiecho gradient-echo sequence. Hepatic and splenic T2* values were assessed in the same gradient multiecho series. Muscle T2* values were assessed in the shoulder girdle muscles adjacent to the heart area. The relationships among splenic T2*, hepatic T2*, cardiac T2* and muscle T2* parameters, serum ferritin levels, age and other parameters were evaluated.
The splenic T2* value correlated with serum ferritin level and the hepatic T2* value (p < 0.001 and p < 0.001, respectively). The splenic T2* value did not correlate with age, cardiac or muscle T2* values, or with spleen size (p = 0.27, 0.21, 0.99, and 0.39, respectively). The muscle T2* value correlated weakly with the serum ferritin level (p = 0.022). The cardiac T2* value was lower and the liver size greater in patients who had undergone splenectomy compared with those who had not (p < 0.001 and 0.001, respectively).
Splenic iron overload correlated with hepatic overload and the serum ferritin level. Splenectomy increased cardiac iron overload and triggered liver enlargement. However, the muscle iron overload was low and the muscles were therefore unaffected by splenectomy.
Background
Severe congenital neutropenia is a rare disease, and autosomal dominantly inherited ELANE mutation is the most frequently observed genetic defect in the registries from North America and ...Western Europe. However, in eastern countries where consanguineous marriages are common, autosomal recessive forms might be more frequent.
Method
Two hundred and sixteen patients with severe congenital neutropenia from 28 different pediatric centers in Turkey were registered.
Results
The most frequently observed mutation was HAX1 mutation (n = 78, 36.1%). A heterozygous ELANE mutation was detected in 29 patients (13.4%) in our cohort. Biallelic mutations of G6PC3 (n = 9, 4.3%), CSF3R (n = 6, 2.9%), and JAGN1 (n = 2, 1%) were also observed. Granulocyte colony‐stimulating factor treatment was given to 174 patients (80.6%). Two patients died with infectious complications, and five patients developed myelodysplastic syndrome/acute myeloblastic leukemia. The mean (± mean standard error) follow‐up period was 129.7 ± 76.3 months, and overall survival was 96.8% (CI, 94.4–99.1%) at the age of 15 years. In Turkey, severe congenital neutropenia mostly resulted from the p W44X mutation in the HAX1 gene.
Conclusion
In Turkey, mutation analysis should be started with HAX1, and if this is negative, ELANE and G6PC3 should be checked. Because of the very high percentage of consanguineous marriage, rare mutations should be tested in patients with a negative mutation screen.
Abstract Bone mineral status has extensively been investigated in adult thalassemics but less in thalassemic children. This study involves measurements of the bone mineral density (BMD), various ...demographic and biochemical parameters in 47 thalassemic children and 50 healthy controls with comparable age, sex, socioeconomic and regional distribution. Patients have significantly higher aspartate aminotransferase, alanine aminotransferase, phosphorous, osteocalcin, serum carboxy terminal teleopeptide fragment of type I collagen, intact parathyroid hormone (iPTH) and ferritin levels while they have significantly lower 25-hydroxy vitamin D (25OH-D), alkaline phosphatase and z-scores both at lumbar and femur compared to controls. Patients with high iPTH (30%) had significantly lower z-scores and 25OH-D while larger osteocalcin. We conclude that a significantly lower BMD in beta-thalassemic children compared with their healthy counterparts is a complex process and may partially attributed to their slower physical development, caused by iron overload and chelation therapy which may influence the liver as well as the endocrine tissues.
Although many pediatric studies on children infected with coronavirus disease 2019 (COVID-19) have been published, the diagnosis, clinical symptoms, laboratory findings, and treatment of COVID-19 in ...children are still unclear.
This study was conducted with an aim to examine the hematological findings of symptomatic pediatric patients diagnosed with COVID-19 in May 2020 at the Pandemic Hospital in Dicle University. Patient records were evaluated retrospectively. This study involved 59 symptomatic pediatric patients with a definite diagnosis of COVID-19 who had positive SARS-CoV-2 RT-PCR test results on nasopharyngeal swab between March 15, 2020 and May 31, 2020.
The records of a total of 10 (16.9%) patients under the age of 1; 21 (35.6%) patients aged 1-10 years, and, 28 (47.5%) patients aged 10-18 years, who had been diagnosed with COVID-19 were evaluated. Based on severity, 35 (59.3%) patients were in the mild group (group 1) and 24 (40.7%) patients were in the moderate-severe group (group 2). The blood parameters of WBC, neutrophil, lymphocyte, monocyte, and thrombocyte counts, the hemoglobin (Hgb) level, and NLR, PLR, MPV, fibrinogen, ferritin, and D-dimer levels were compared between groups, the difference was not statistically significant (P > .05). LDH was higher in group 2 (P = .014).
Since children infected with COVID-19 show mild clinical symptoms or are asymptomatic, fewer pediatric patients may be detected than adults. Therefore, it should be known that the laboratory findings typical for adults may not accompany the disease in pediatric cases. More studies are needed to determine the most appropriate COVID-19 treatment approach for children, as hospitalization history and testing rates are less reported among children.
To study the clinical, laboratory, and treatment features observed in pediatric patients with tuberculous meningitis in Turkey. Study Design. Retrospective case review study.
Review of medical ...records for demographic data, medical history, clinical manifestations, auxiliary test results, complications, and treatment of 214 children with central nervous system tuberculosis (TB) admitted to Dicle University's hospital between August 1988 and February 1996.
Of the 214 patients with tuberculous meningitis, 112 (52%) were male. The mean age at presentation was 4. 1 years, with 165 patients (77%) younger than 5 years. Twenty-two patients (10%) were in the first stage of the disease, 120 (56%) in the second, and 72 (34%) in the third. Our epidemiologic data showed that 141 (66%) of the patients had a family history of TB, and 64 (30%) had a Mantoux skin test result of >10 mm of induration. Radiographic studies demonstrated abnormal chest findings in 187 patients (87%) (hilar adenopathy, 33%; infiltrates, 33%; miliary pattern, 20%; and pleural effusions, 1%, and 172 (80%) cases with hydrocephalus, 26% with parenchymal disease, 15% with basilar meningitis, and 2% with tuberculomas. Only 22 (13%) of 164 children had a positive acid-fast bacilli smear in cerebrospinal fluid, and Mycobacterium tuberculosis was isolated in 49 patients (30%). All the patients were treated with Isoniazid, rifampin, and streptomycin or pyrazinamide for 2 months, followed by 10 months of Isoniazid and rifampin alone. Also, all the patients received adjuvant treatment with steroids early in the course of treatment, and 140 of 172 cases with hydrocephalus had surgical intervention. The overall mortality rate was 23%.
One or more of these findings: a family history of TB, positive tuberculin skin test results, abnormal cranial computed tomography, and/or cerebrospinal fluid analysis compatible with TBM were found in all but 3 children in our study. central nervous system, tuberculous meningitis, diagnosis, hydrocephalus, children.
Abstract
Background: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-β-d-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury ...molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in children with β-thalassemia major (β-TM). Materials and methods: Totally, 52 patients (29 boys, 23 girls) with β-TM and 29 healthy controls (3-17 years) were included. Various demographic characteristics and blood transfusions/year, disease duration, and chelation therapy were recorded. Serum urea, creatinine, electrolytes, and ferritin and urinary creatinine, protein, calcium, phosphorus, sodium, potassium, and uric acid in first morning urine samples were measured and estimated glomerular filtration rate (eGFR) was calculated. Routine serum and urinary biochemical variables, urinary NAG to Creatinine (UNAG/Cr), UNGAL/Cr, UKIM-1/Cr, and UL-FABP/Cr ratios were determined. Results: Patients had similar mean serum urea, creatinine and eGFR levels compared with controls (p > 0.05 for all). The mean urinary protein to creatinine (UProtein/Cr) ratio was significantly higher in patients compared to the healthy subjects (0.13 ± 0.09 mg/mg and 0.07 ± 0.04 mg/mg, respectively; p < 0.001). Significantly increased UNAG/Cr (0.48 ± 0.58 vs. 0.23 ± 0.16, p = 0.026) and UNGAL/Cr (22.1 ± 18.5 vs. 11.5 ± 6.17, p = 0.01) ratios were found in β-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or UKIM-1/Cr and UL-FABP/Cr ratios between patients and controls (p > 0.05). Significant correlations were found between urinary biomarkers and urinary electrolytes (p < 0.05). Conclusions: Our results suggest that urinary NAG and NGAL may be considered to be reliable markers to monitor renal injury in β-TM patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Objectives
To evaluate the long‐term efficacy and safety of deferasirox therapy in a large observational cohort of children with transfusion‐dependent thalassemia (TDT) and sickle cell anemia (SCA) ...in Turkey.
Methods
This was a multicenter, prospective cohort study including TDT and SCA patients aged 2‐18 years with iron overload (≥100 mL/kg of pRBC or a serum ferritin SF level >1000 μg/L) receiving deferasirox. Patients were followed for up to 3 years according to standard practice.
Results
A total of 439 patients were evaluated (415 94.5% TDT, 143 32.6% between 2 and 6 years). Serum ferritin levels consistently and significantly decreased across 3 years of deferasirox therapy from a median of 1775.5 to 1250.5 μg/L (P < 0.001). Serum ferritin decreases were noted in TDT (1804.9 to 1241 μg/L), SCA (1655.5 to 1260 μg/L), and across age groups of 2‐6 years (1971.5 to 1499 μg/L), 7‐12 years (1688.5 to 1159.8 μg/L), and 13‐18 years (1496.5 to 1107 μg/L). Serum ferritin decreases were also noted for all deferasirox dose groups but only significant in patients with doses ≥30 mg/kg/d (n = 120, −579.6 median reduction, P < 0.001). Only 9 (2%) patients had adverse events suspected to be related to deferasirox. Serum creatinine slightly increased but remained within the normal range.
Conclusions
Deferasirox has long‐term efficacy and safety in children with TDT and SCA, although higher doses (≥30 mg/kg/d) may be required to achieve iron balance.
The aim of this study was to investigate the urine levels of human kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-β-D-glucosaminidase (NAG), and ...liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA).
Thirty-five children with IDA and 32 matched healthy controls were recruited. We assessed complete blood count, serum iron, iron-binding capacity, ferritin, serum levels of urea, creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), and glucose levels. Estimated glomerular filtration rate (eGFR) was calculated. Urinary NAG, NGAL, KIM-1, and L-FABP were measured and divided by urine creatinine for comparisons.
There were no significant differences in serum urea, Cr, or eGFR between the IDA group and the control group (p>0.05, for all). IDA patients had significantly higher urine NGAL/Cr, L-FABP/Cr, KIM-1/Cr, and NAG/Cr compared with the control group (p<0.05). There were significant negative correlations between hemoglobin, hematocrit, red blood cell count, and urine NGAL/Cr, NAG/Cr, L-FABP/Cr, KIM-1/Cr levels (p<0.05).
Higher urinary kidney injury molecule levels in IDA patients suggest a possible subclinical renal injury in pediatric IDA patients whose renal functions and serum electrolytes were normal.
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