Deferasirox in children with transfusion-dependent thalassemia or sickle cell anemia: A large cohort real-life experience from Turkey (REACH-THEM).

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.

Homozygous c.130-131 ins A (pW44X) mutation in the HAX1 gene as the most common cause of congenital neutropenia in Turkey: Report from the Turkish Severe Congenital Neutropenia Registry.

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.

MRI-based evaluation of the factors leading to pituitary iron overload in patients with thalassemia major.

AIM: Given the lack of studies evaluating pituitary iron overload in patients with thalassemia major, we used magnetic resonance imaging (MRI) to evaluate these patients and the factors affecting the disease process. MATERIALS AND METHODS: The 84 patients with ß-thalassemia major who were included in this study were referred to our clinic for cardiac and hepatic T2(*) MRI. T2(*)-weighted images of the pituitary gland, heart, and liver were obtained using a 1.5-tesla MRI unit and a multi-echo gradient-echo sequence. Associations between pituitary T2(*), cardiac T2(*), hepatic T2(*), pituitary height, serum ferritin (SF) level, patient age, and other demographic findings were assessed. RESULTS: Pituitary T2(*) values correlated with hepatic T2(*) values, cardiac T2(*) values, SF level, and patient age (P≤0.001, 0.001, 0.001, 0.01, respectively) but not with pituitary height (P=0.76). Pituitary and cardiac T2(*) values were lower in the subset of patients who underwent splenectomy (P=0.046 and P=0.002, respectively). CONCLUSION: Pituitary iron overload rapidly increases during puberty and in this study correlated with cardiac and hepatic T2(*) values, patient age, SF level, and liver size, but not with the height of the pituitary. Pituitary iron overload also increases following splenectomy. Together, these findings indicate that numerous factors contribute to pituitary iron overload.

Urinary Kidney Injury Molecules in Children with Iron-Deficiency Anemia.

BACKGROUND: 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-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA). MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Urinary early kidney injury molecules in children with beta-thalassemia major.

BACKGROUND: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-ß-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 ß-thalassemia major (ß-TM). MATERIALS AND METHODS: Totally, 52 patients (29 boys, 23 girls) with ß-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 (U(NAG/Cr)), U(NGAL/Cr), U(KIM-1/Cr), and U(L-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 (U(Protein/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 U(NAG/Cr) (0.48 ± 0.58 vs. 0.23 ± 0.16, p = 0.026) and U(NGAL/Cr) (22.1 ± 18.5 vs. 11.5 ± 6.17, p = 0.01) ratios were found in ß-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or U(KIM-1/Cr) and U(L-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 ß-TM patients.

The effects of pomegranate and carvacrol on methotrexate-induced bone marrow toxicity in rats.

PURPOSE: The aim of this study was to evaluate the effects of pomegranate (PMG) extract and carvacrol (CARV) on methotrexate (MTX)-induced oxidative stress and bone marrow toxicity. METHODS: Wistar albino rats (32 rats) were divided into four groups (n=8): Group 1 was control; Group 2 was given a single intraperitoneal injection of methotrexate (20 mg/kg); Group 3 was treated with carvacrol (73 mg/kg i.p.) one day before MTX (20 mg/kg i.p.) injection; and, Group 4 received a single dose of MTX (20 mg/kg i.p) while PMG was administered orally for seven days at 225 mg/kg. After animals were euthanized, blood samples were taken to evaluate hematological parameters and oxidative stress. In addition, the femur was cropped and bone marrow was extracted for examination. RESULTS: White blood cell count, hemoglobin, hematocrit and platelet count were found to be decreased in the MTX group, but these changes were prevented in the groups that received CARV and PMG. Furthermore, decreased bone marrow cellularity was found in the groups treated with MTX, whereas the PMG and CARV groups had cellularity similar to controls. Strikingly, oxidative stress increased in the MTX group, but was ultimately decreased in the rats that received the antioxidants PMG and CARV. CONCLUSION: Carvacrol and PMG were found to be protective against methotrexate-induced oxidative bone marrow damage. Use of these antioxidants, in combination with chemotherapeutics, may help to reduce some adverse effects of methotrexate.

Outcome of modified St Jude total therapy 13A for childhood acute lymphoblastic leukemia in the southeast region of Turkey.

OBJECTIVE: To fill the gap in the current data on childhood acute lymphoblastic leukemia (ALL) in low-income and middle-income countries. METHODS: This study included 106 children between the ages of 1 and 17 years with newly diagnosed ALL monitored between 1999 and 2010. All the patients were treated with the modified St Jude Total 13A treatment plan at the Pediatric Hematology Clinic at Harran University. RESULTS: Sixty-eight (64.2%) patients were boys and 38 (35.8%) were girls. The median age at diagnosis was 5.9 ± 3.7 years. Thirty-eight (35.8%) children were classified as standard risk, 53 (39.3%) were intermediate risk, and 15 (14.2%) were high risk. Thirteen (12.3%) children died in induction before the remission date (43 d of remission induction). Of all the 93 (100%) patients who completed remission induction therapy and whose bone marrow were in remission, 5 (4.7%) had a bone marrow relapse, 1 (0.9%) had a retinal relapse, and 5 (4.7%) had secondary acute myeloid leukemia. At a median follow-up of 44 months (range, 0.36 to 135.5 mo), the estimated 5-year overall survival and event-free survival were 77.4 ± 5% and 68.9 ± 6.5%, respectively. The estimated 5-year overall survival for boys and girls was 76.5 ± 6% and 65.8 ± 8%, respectively (P = 0.182). CONCLUSIONS: St Jude Total 13A treatment protocols to treat childhood ALL can be successfully adapted, which suggests that such an approach may be useful in low socioeconomic regions; however, it should be noted that secondary leukemia can occur at a high rate.

The clinical findings and prophylactic treatment in children with factor X deficiency.

Factor X (FX) is the component of both extrinsic and intrinsic coagulation cascade and is the first enzyme of the common pathway which results in thrombus. Congenital FX deficiency (FXD) is an extremely rare coagulation defect. In this study, we aimed to investigate the clinical and laboratory data of the patients diagnosed with FXD. The files of the 15 patients (7 female, 8 male) diagnosed and followed up for FXD within the last 4 years were evaluated retrospectively. The mean age of the patients was 29 months (min-max:1-144 months). The most presenting complaints were easy bruisability (n = 8; 53%) and epistaxis (n = 8; 53%). FX levels were <1% in six patients, 1-5% in four patients, and >5% in five patients. Heparin added-Protrombin Complex was used for prophlaxy (n = 11; 73%). Any treatment-related complication was not observed. Heparin-added PCC can be used safely for effective prophlaxy. We suggest that family history is important when considering prophlaxy and in patients with life-threatening bleeding or with FXD sibling the prophlaxy should be introduced in the early course.

Clinical Characteristics and Outcomes of Cancer Cases Among Syrian Refugees From Southern Turkey.

Importance: Cancer was a common noncommunicable disease in Syria before the present conflict and is now a major disease burden among 3.6 million Syrian refugees in Turkey. Data to inform health care practice are needed. Objective: To explore sociodemographic characteristics, clinical characteristics, and treatment outcomes of Syrian patients with cancer residing in the southern border provinces of Turkey hosting more than 50% of refugees. Design, Setting, and Participants: This was a retrospective hospital-based cross-sectional study. The study sample consisted of all adult and children Syrian refugees diagnosed and/or treated for cancer between January 1, 2011, and December 31, 2020, in hematology-oncology departments of 8 university hospitals in the Southern province of Turkey. Data were analyzed from May 1, 2022, to September 30, 2022. Main Outcomes and Measures: Demographic characteristics (date of birth, sex, and residence), date of first cancer-related symptom, date and place of diagnosis, disease status at first presentation, treatment modalities, date and status at last hospital visit, and date of death. The International Statistical Classification of Diseases and Related Health Problems, Tenth Revision and International Classification of Childhood Cancers, Third Edition, were used for the classification of cancer. The Surveillance, Epidemiology, and End Results system was applied for staging. The diagnostic interval was defined as the number of days from first symptoms until the diagnosis. Treatment abandonment was documented if the patient did not attend the clinic within 4 weeks of a prescribed appointment throughout the treatment. Results: A total of 1114 Syrian adult and 421 Syrian children with cancer were included. The median age at diagnosis was 48.2 (IQR, 34.2-59.4) years for adults and 5.7 (IQR, 3.1-10.7) years for children. The median diagnostic interval was 66 (IQR, 26.5-114.3) days for adults and 28 (IQR, 14.0-69.0) days for children. Breast cancer (154 [13.8%]), leukemia and multiple myeloma (147 [13.2%]), and lymphoma (141 [12.7%]) were common among adults, and leukemias (180 [42.8%]), lymphomas (66 [15.7%]), and central nervous system neoplasms (40 [9.5%]) were common among children. The median follow-up time was 37.5 (IQR, 32.6-42.3) months for adults and 25.4 (IQR, 20.9-29.9) months for children. The 5-year survival rate was 17.5% in adults and 29.7% in children. Conclusions and Relevance: Despite universal health coverage and investment in the health care system, low survival rates were reported in this study for both adults and children with cancer. These findings suggest that cancer care in refugees requires novel planning within national cancer control programs with global cooperation.

Evaluation of retinal nerve fiber layer and choroidal thickness with spectral domain optical coherence tomography in children with sickle cell anemia.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Evaluation of Hematological Parameters of Children Diagnosed with COVID-19: Single-Center Experience.

OBJECTIVE: 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. MATERIALS AND METHODS: 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. RESULTS: 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). CONCLUSION: 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.

Prolidase activity and oxidative status in patients with thalassemia major.

AIM: Prolidase is a specific imidodipeptidase involved in collagen degradation. The increase in the enzyme activity is believed to be correlated with the increased intensity of collagen degradation. The study aimed to evaluate the relationship between prolidase activity and oxidative status in patients with thalassemia major. METHODS: Comparison was made between 87 patients diagnosed with thalassemia major and 33 healthy children of similar age and gender. Mean age of the subjects was 7.5+/-4.3 years in the group of patients with thalassemia major and 8.9+/-3.1 years in the control group. Serum prolidase activity was measured spectrophotometrically. Oxidative status was determined using total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) measurement. RESULTS: Prolidase activity was significantly increased in patients with thalassemia major (53.7+/-8.7 U/l) compared to the control group (49.2+/-7.2 U/l, P<0.001). TOS was significantly increased in the patient group (5.31+/-3.14 mmol H2O2 equiv./l) compared to the control group (3.49+/-2.98 mumol H2O2 equiv./l) and the OSI was also significantly increased in the patient group (3.86+/-3.28 arbitrary unit) compared to the control group (2.53+/-2.70 arbitrary unit) (P<0.0001 and P<0.001, respectively), while there were no significant differences between the patient (1.61+/-0.30 mumol Trolox equiv./l) and control (1.64+/-0.33 mumol Trolox equiv./l) groups with respect to TAC. CONCLUSION: Significant increases in prolidase activity in patients with thalassemia major may constitute a key parameter in demonstrating a disorder of the collagen metabolism.

Evaluation of the relationship between splenic iron overload and liver, heart and muscle features evident on T2*-weighted magnetic resonance imaging.

BACKGROUND: Splenic iron overload is the most common clinical condition in patients with thalassemia. However, few studies of the effects of splenectomy have been published. OBJECTIVES: 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). MATERIAL AND METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Outcomes of Eltrombopag Treatment and Development of Iron Deficiency in Children with Immune Thrombocytopenia in Turkey

Objective: Immune thrombocytopenia (ITP) is a rare autoimmune disease and hematologic disorder characterized by reduced platelet counts that can result in significant symptoms, such as bleeding, bruising, epistaxis, or petechiae. The thrombopoietin receptor agonist eltrombopag (EPAG) is a second-line agent used to treat chronic ITP purpura in adults and children. Materials and Methods: The present retrospective study evaluated the efficacy, safety, and side effects of EPAG treatment in pediatric patients with acute refractory and chronic immune thrombocytopenia, particularly focusing on iron-deficiency anemia. Results: The diagnosis was chronic ITP in 89 patients and acute refractory ITP in 16 patients. The mean age of patients was 9.5±4.5 years (minimum-maximum: 1.2-18 years) at the beginning of EPAG treatment. The overall response rate was 74.3% (n=78). The mean time for platelet count of ≥50x109/L was 11.6±8 weeks (range: 1-34 weeks). The treatment was stopped for 27 patients (25.7%) at an average of 6.8±9 months (range: 1-38 months). The reason for discontinuation was lack of response in 18 patients, nonadherence in 4 patients, and hepatotoxicity in 2 patients. Response to treatment continued for an average of 4 months after cessation of EPAG in 3 patients. Conclusion: Results of the current study imply that EPAG is an effective therapeutic option in pediatric patients with acute refractory and chronic ITP. However, patients must be closely monitored for response and side effects during treatment, and especially for iron deficiency.

Paraoxonase and arylesterase activity with oxidative status in children with thalassemia major.

PURPOSE: The aim of this study was to study paraoxonase and arylesterase activities along with oxidative status parameters, and to find out whether there is any increased susceptibility to atherogenesis, which might be reflected with increased oxidative stress and decreased serum paraoxonase/arylesterase activity in beta-thalassemia major (BTM) patients. PATIENTS AND METHODS: Eighty-seven patients with BTM and 33 healthy individuals were enrolled in the study. RESULTS: Paraoxonase and arylesterase activities were significantly lower in BTM patients than controls (for all P<0.0001), whereas total oxidant status, total peroxide concentration levels, and oxidative stress index were significantly higher (P<0.0001, <0.0001, and <0.001, respectively). Correlations were found between serum iron and ferritin and levels of total oxidant status in BTM patients. Significant correlation was found with serum total peroxide concentration levels and paraoxonase and arylesterase activities in patients with BTM. CONCLUSIONS: It was seen that oxidative stress increases, while serum paraoxonase activity is decreased in BTM patients. Decrease in paraoxonase activity seems to be associated with both the degree of oxidative stress and anemia. BTM patients may be more prone to development of atherogenesis because of low serum paraoxonase/arylesterase activity.

Severe osteoporosis and high level TSH in a child before the diagnosis of acute lymphoblastic leukemia.

Osteoporosis in children is rare and mostly secondary to such conditions as prolonged immobilization, malabsorption syndromes, corticosteroid excess, osteogenesis imperfecta, celiac disease, Turner syndrome, and malignancy. Idiopathic juvenile osteoporosis (IJO) is a very rare condition of primary bone demineralization that presents in childhood. IJO, a disease of unknown etiology, manifests typically by pain, bone deformities, and fractures. Diagnosis of IJO was made by excluding other common causes of osteoporosis in this age. Bisphosphonates, calcitriol, fluoride, and calcitonin have been administered therapeutically, but the results were equivocal. Usually the disease remits by itself. Patient that has serious osteoporosis and high thyroid stimulating hormone level was diagnosed as IJO by eliminating secondary reasons. We report this case, whose symptoms were disappeared after parenteral pamidronat treatment, and he was reexamined owing to anemia and trombositopenia, and diagnosed as B-cell acute lymphoblastic leukemia, just to emphasis the importance of close follow-ups of IJO patients.

A National Registry of Thalassemia in Turkey: Demographic and Disease Characteristics of Patients, Achievements, and Challenges in Prevention.

OBJECTIVE: The Turkish Society of Pediatric Hematology set up a National Hemoglobinopathy Registry to demonstrate the demographic and disease characteristics of patients and assess the efficacy of a hemoglobinopathy control program (HCP) over 10 years in Turkey. MATERIALS AND METHODS: A total of 2046 patients from 27 thalassemia centers were registered, of which 1988 were eligible for analysis. This cohort mainly comprised patients with ß-thalassemia major (n=1658, 83.4%) and intermedia (n=215, 10.8%). RESULTS: The majority of patients were from the coastal areas of Turkey. The high number of patients in Southeastern Anatolia was due to that area having the highest rates of consanguineous marriage and fertility. The most common 11 mutations represented 90% of all ß-thalassemia alleles and 47% of those were IVS1-110(G->A) mutations. The probability of undergoing splenectomy within the first 10 years of life was 20%, a rate unchanged since the 1980s. Iron chelators were administered as monotherapy regimens in 95% of patients and deferasirox was prescribed in 81.3% of those cases. Deferasirox administration was the highest (93.6%) in patients aged <10 years. Of the thalassemia major patients, 5.8% had match-related hemopoietic stem cell transplantation with a success rate of 77%. Cardiac disease was detected as a major cause of death and did not show a decreasing trend in 5-year cohorts since 1999. CONCLUSION: While the HCP has been implemented since 2003, the affected births have shown a consistent decrease only after 2009, being at lowest 34 cases per year. This program failure resulted from a lack of premarital screening in the majority of cases. Additional problems were unawareness of the risk and misinformation of the at-risk couples. In addition, prenatal diagnosis was either not offered to or was not accepted by the at-risk families. This study indicated that a continuous effort is needed for optimizing the management of thalassemia and the development of strategies is essential for further achievements in the HCP in Turkey.

Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency. / Niveles de moléculas de detección temprana de daño renal en la orina en niños con deficiencia de vitamina B12.

The aim of this study was to investigate urine early kidney injury molecules, including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency (CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes, B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR) was calculated. Urine protein, electrolytes, andurinary early markers were measured. Patients with CD had significantly higher urine electrolyte/Cr ratios (p <0.05). Significantly higher urinary KIM-1/Cr, L-FABP/Cr, NAG/Cr and NGAL/Cr were found in CD group (p <0.05). Significant negative correlations were found between levels of serum B12 and urinary markers in the patients (p <0.05). Increased urinary kidney injury molecules and electrolytes in children with B12 deficiency suggest a possible subclinical renal dysfunction, which cannot be determined by conventional kidney function tests.

El objetivo de este estudio fue investigar los niveles de moléculas de detección temprana de daño renal en la orina, que incluyen la molécula 1 de lesión renal en humanos (KIM-1), la proteína hepática transportadora de ácidos grasos (L-FABP), el N-acetil-b-D-glucosaminidasa A (NAG) y la lipocalina asociada con la gelatinasa de neutrófilos (NGAL), en niños con deficiencia de vitamina B12 (cobalamina).Seincluyeron 12 niños condeficiencia de vitamina B12 y 20 niños sanos en el grupo de referencia emparejado. Se registraron los parámetros hematológicos, la urea en suero, la creatinina (Cr), los electrolitos, y los niveles de vitamina B12 y folato. Se calculó la tasa de filtración glomerular estimada (TFGe). Se midieronlosnivelesdeproteínas, electrolitos y marcadoresde deteccióntemprana en laorina. Lospacientescon deficiencia de cobalamina tenían un cociente significativamente superior de electrolitos/Cr en la orina (p < 0,05). Se hallaron niveles significativamente superiores de KIM-1/Cr, L-FABP/ Cr, NAG/Cr y N GAL / Cr en la orina en el grupo con deficiencia de cobalamina (p < 0,05). En estos pacientes, también se hallaron correlaciones negativas significativas entre los niveles de vitamina B12 en suero y los marcadores en la orina (p < 0,05). El aumento de los electrolitos y de las moléculas marcadoras de lesión renal en la orina en los niños con deficiencia de vitamina B12 sugiere una posible disfunción renal subclínica, que no puede determinarse mediante las pruebas funcionales renales convencionales.