COVID-19 disease in children and adolescents following allogeneic hematopoietic stem cell transplantation: A report from the Turkish pediatric bone marrow transplantation study group.

BACKGROUND: Data on the risk factors and outcomes for pediatric patients with SARS-CoV-2 infection (COVID-19) following hematopoietic stem cell transplantation (HSCT) are limited. OBJECTIVES: The study aimed to analyze the clinical signs, risk factors, and outcomes for ICU admission and mortality in a large pediatric cohort who underwent allogeneic HSCT prior to COVID-19 infection. METHOD: In this nationwide study, we retrospectively reviewed the data of 184 pediatric HSCT recipients who had COVID-19 between March 2020 and August 2022. RESULTS: The median time from HSCT to COVID-19 infection was 209.0 days (IQR, 111.7-340.8; range, 0-3845 days). The most common clinical manifestation was fever (58.7%). While most patients (78.8%) had asymptomatic/mild disease, the disease severity was moderate in 9.2% and severe and critical in 4.4% and 7.6%, respectively. The overall mortality was 10.9% (n: 20). Deaths were attributable to COVID-19 in nine (4.9%) patients. Multivariate analysis revealed that lower respiratory tract disease (LRTD) (OR, 23.20, p: .001) and lymphopenia at diagnosis (OR, 5.21, p: .006) were risk factors for ICU admission and that HSCT from a mismatched donor (OR, 54.04, p: .028), multisystem inflammatory syndrome in children (MIS-C) (OR, 31.07, p: .003), and LRTD (OR, 10.11, p: .035) were associated with a higher risk for COVID-19-related mortality. CONCLUSION: While COVID-19 is mostly asymptomatic or mild in pediatric transplant recipients, it can cause ICU admission in those with LRTD or lymphopenia at diagnosis and may be more fatal in those who are transplanted from a mismatched donor and those who develop MIS-C or LRTD.

Identification of the molecular etiology in rare congenital hemolytic anemias using next-generation sequencing with exome-based copy number variant analysis.

OBJECTIVES: In congenital hemolytic anemias (CHA), it is not always possible to determine the specific diagnosis by evaluating clinical findings and conventional laboratory tests. The aim of this study is to evaluate the utility of next-generation sequencing (NGS) and clinical-exome-based copy number variant (CNV) analysis in patients with CHA. METHODS: One hundred and forty-three CHA cases from 115 unrelated families referred for molecular analysis were enrolled in the study. Molecular analysis was performed using two different clinical exome panels in 130 patients, and whole-exome sequencing in nine patients. Exome-based CNV calling was incorporated into the traditional single-nucleotide variant and small insertion/deletion analysis pipeline for NGS data in 92 cases. In four patients from the same family, the PK Gypsy variant was investigated using long-range polymerase chain reaction. RESULTS: Molecular diagnosis was established in 86% of the study group. The most frequently mutated genes were SPTB (31.7%) and PKLR (28.5%). CNV analysis of 92 cases revealed that three patients had different sizes of large deletions in the SPTB and six patients had a deletion in the PKLR. CONCLUSIONS: In this study, NGS provided a high molecular diagnostic rate in cases with rare CHA. Analysis of the CNVs contributed to the diagnostic success.

Clinical features and risk factors of hepatic sinusoidal obstruction syndrome in children after hematopoietic stem cell transplantation: A single-center experience.

Hepatic sinusoidal obstruction syndrome (SOS) is an illness with serious life effects that develops after hematopoietic stem cell transplantation (HSCT). We investigated the risk factors and clinical features of hepatic SOS in children following HSCT in 210 children who underwent allogeneic or autologous HSCT between 2009 and 2021 were analyzed in the context of SOS. The syndrome developed in 22 (10.4%) patients:frequently in neuroblastoma [24% (5/21)], hemophagocytic lymphohistiocytosis [57% (4/7)], and thalassemia major [22% (7/31)]. The median time from HSCT to diagnosis was 16 (6-38) days. Severe disease occurred in 8 (36%) patients, and mild/moderate in 14 (64%) and 4 patients died (18%). In univariate analyses, patient's age ≤ 2 years [odds ratio (OR)= 3.043, P = 0.028], pretransplant AST and ALT levels > 100 U/L (OR=3.576, P = 0.045), and chemotherapy/radiotherapy to abdomen before transplantation (OR = 3.162, P = 0.044) were determined as risk factors. In multivariate analysis, pre-transplant AST and ALT levels > 100 U/L (OR = 16.04, P = 0.010) and ferritin levels over 1000 mg/dl (OR=5.15, P = 0.047) were significant. The only independent risk factor on mortality was the age ≤ 2 years (P = 0.001). Although our study confirmed several risk factors for SOS, we failed to achieve some well-known risk factors. Precautions should be taken considering the factors affecting liver function before transplantation and the risk of SOS in infants receiving chemotherapy and radiotherapy before transplantation, such as neuroblastoma in which comparable results in respect to the chemotherapy only. The risk factors should be fully elucidated in multicenter studies to improve preventive and therapeutic strategies.

Expanding the clinical and immunological phenotypes of PAX1-deficient SCID and CID patients.

Paired box 1 (PAX1) deficiency has been reported in a small number of patients diagnosed with otofaciocervical syndrome type 2 (OFCS2). We described six new patients who demonstrated variable clinical penetrance. Reduced transcriptional activity of pathogenic variants confirmed partial or complete PAX1 deficiency. Thymic aplasia and hypoplasia were associated with impaired T cell immunity. Corrective treatment was required in 4/6 patients. Hematopoietic stem cell transplantation resulted in poor immune reconstitution with absent naïve T cells, contrasting with the superior recovery of T cell immunity after thymus transplantation. Normal ex vivo differentiation of PAX1-deficient CD34+ cells into mature T cells demonstrated the absence of a hematopoietic cell-intrinsic defect. New overlapping features with DiGeorge syndrome included primary hypoparathyroidism (n = 5) and congenital heart defects (n = 2), in line with PAX1 expression during early embryogenesis. Our results highlight new features of PAX1 deficiency, which are relevant to improving early diagnosis and identifying patients requiring corrective treatment.

Thalassemia-free and graft-versus-host-free survival: outcomes of hematopoietic stem cell transplantation for thalassemia major, Turkish experience.

We report the national data on the outcomes of hematopoietic stem cell transplantation (HSCT) for thalassemia major (TM) patients in Turkey on behalf of the Turkish Pediatric Stem Cell Transplantation Group. We retrospectively enrolled 1469 patients with TM who underwent their first HSCT between 1988 and 2020 in 25 pediatric centers in Turkey. The median follow-up duration and transplant ages were 62 months and 7 years, respectively; 113 patients had chronic graft versus host disease (cGVHD) and the cGVHD rate was 8.3% in surviving patients. Upon the last visit, 30 patients still had cGvHD (2.2%). The 5-year overall survival (OS), thalassemia-free survival (TFS) and thalassemia-GVHD-free survival (TGFS) rates were 92.3%, 82.1%, and 80.8%, respectively. cGVHD incidence was significantly lower in the mixed chimerism (MC) group compared to the complete chimerism (CC) group (p < 0.001). In survival analysis, OS, TFS, and TGFS rates were significantly higher for transplants after 2010. TFS and TGFS rates were better for patients under 7 years and at centers that had performed over 100 thalassemia transplants. Transplants from matched unrelated donors had significantly higher TFS rates. We recommend HSCT before 7 years old in thalassemia patients who have a matched donor for improved outcomes.

Different Kinetics and Risk Factors for Isolated Extramedullary Relapse after Allogeneic Hematopoietic Stem Cell Transplantation in Children with Acute Leukemia.

Relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains the most frequent cause of post-transplantation mortality. Isolated extramedullary (EM) relapse (iEMR) after HSCT is relatively rare and not well characterized, particularly in pediatric patients. We retrospectively analyzed 1527 consecutive pediatric patients with acute leukemia after allo-HSCT to study the incidence, risk factors, and outcome of iEMR compared with systemic relapse. The 5-year cumulative incidence of systemic relapse (either bone marrow [BM] only or BM combined with EMR) was 24.8%, and that of iEMR was 5.5%. The onset of relapse after allo-HSCT was significantly longer in EM sites than in BM sites (7.19 and 5.58 months, respectively; P = .013). Complete response (CR) 2+/active disease at transplantation (hazard ratio [HR], 3.1; P < .001) and prior EM disease (HR, 2.3; P = .007) were independent risk factors for iEMR. Chronic graft-versus-host disease reduced the risk of systemic relapse (HR, 0.5; P = .043) but did not protect against iEMR. The prognosis of patients who developed iEMR remained poor but was slightly better than that of patients who developed systemic relapse (3-year overall survival, 16.5% versus 15.3%; P = .089). Patients experiencing their first systemic relapse continued to have further systemic relapse, but only a minority progressed to iEMR, whereas those experiencing their iEMR at first relapse developed further systemic relapse and iEMR at approximately similar frequencies. A second iEMR was more common after a first iEMR than after a first systemic relapse (58.8% versus 13.0%; P = .001) and was associated with poor outcome. iEMR has a poor prognosis, particularly after a second relapse, and effective strategies are needed to improve outcomes.

Flow cytometric analysis of platelet surface glycoproteins in the diagnosis of thirty-two Turkish patients with Glanzmann thrombasthenia: a multicenter experience

Background/aim: Glanzmann thrombasthenia (GT) is a rare autosomal recessively inherited bleeding disorder characterized by the quantitative (type 1 and type 2) or qualitative (type 3) deficiency in platelet membrane glycoprotein (GP) IIb/IIIa (CD41a/CD61) fibrinogen receptors. In type 1, 2, and 3, CD41a/CD61 expression is 5%, 5%­20% and above 20%, respectively. In this study, diagnosis of GT was confirmed and subgroups were identified in 32 Turkish patients by flow cytometry analysis. Materials and methods: CD41a/CD61 expression levels in platelet-rich plasma (PRP) obtained from peripheral venous EDTA blood samples were analyzed with a BD FACSCanto II flow cytometer (Becton Dickinson, Franklin Lakes, NJ, USA). GT subgroup analysis was performed by counting 50,000 events in the BD FACSDiva Software v6.1.3 program of the instrument. Results: In the present study, in blood samples of 32 patients from 23 families with GT and 22 healthy controls, co-expression levels of CD41a and CD61 in PRP was analyzed. 12 out of 23 families were consistent with type 1 GT (52.2%), 4 were consistent with type 2 GT (17.4%), and 7 were consistent with type 3 GT (30.4%). Conclusion: Especially due to consanguineous marriages, GT with various glycoprotein levels may be detected. As a result of the flow cytometry analysis of the present study with the highest GT patient population in Turkey, type 1 GT patients were the most common subgroup. In the determination of the GT subgroups; especially in the detection of type 3 GT, flow cytometry is the most sensitive glycoprotein analysis method. In addition to light transmission aggregometry, CD41a/CD61 study by flow cytometer confirms diagnosis when mutation analysis cannot be performed.

Clinical follow-up of children with high vitamin B12 values: should we worry?

BACKGROUND: Requests of Vitamin B12 test increased with the widespread use of autoanalysers. Although the cause of requests was deficiency suspicions, an important ratio of high levels of Vitamin B12 were reported to physicians by laboratory. Ratios of values of high Vitamin B12 among test request in adults are reported as 14- 20% in present three monocentre studies and one multicentre study. There is no report on children with high vitamin B12 for both ratio in lab requests or clinical follow up. METHODS: We evaluated the records of 40 children (23 male /17 female) with high B12 values ( > 1000 pg/ ml) retrospectively. Children were otherwise healthy children and were seen at outpatient pediatric clinics. Additionally, vitamin B12 values of 13 acute lymphoblastic leukemia patients at diagnosis time were retrieved to enlighten possible role of lymphocytes. RESULT: Children did not have any malign or chronic diseases causing the high Vitamin B12 values. Holotranscobalamin levels were normal or slightly above. Two patients did develop leukemia later. Our follow up showed that high vitamin B12 values slightly decreased at 3 months and then remained unchanged later. The high numbers of T and B cells are not the source of vitamin B12 elevation. CONCLUSIONS: Our study suggests that high-vitamin B12 values are usually benign in children but some patients may develop leukemia later. We suggest that patients should be followed up for some time after testing for severe hematological diseases.

Neonates born to mothers with immune thrombocytopenia: 11 years experience of a single academic center.

: A major problem associated with immune thrombocytopenic purpura (ITP) in pregnancy is neonatal thrombocytopenia. We analyzed newborns born to mothers with ITP and examined predictive factors for thrombocytopenia. This retrospective study was performed in a single academic center from January 2007 to January 2018. Pregnant women with ITP and their babies are included. All neonates had a complete blood count and cranial ultrasound (USG) performed. Twenty seven neonates of 22 mothers were evaluated. A total of 23 (85%) of neonates were thrombocytopenic (<150 × 10/l) and in 20 (74%) platelet count was below 50 × 10/l. Median platelet count was 30 (4-300) × 10/l. One baby experienced intracranial hemorrhage, eight (29.6%) had minor bleeding. When babies with and without minor bleeding were compared; no significant difference was found regarding maternal age, duration of ITP, lowest and 'before delivery' platelet count, treatment during pregnancy and splenectomy. Cutoff value of platelet count for bleeding was calculated as 27 × 10/l with a sensitivity of 0.88 and specifity of 0.79. Strong correlation for postnatal thrombocytopenia was detected among siblings. Although the incidence of neonatal thrombocytopenia might be high, the incidence of poor neonatal outcomes is extremely low. Neonatal thrombocytopenia does not rely on maternal profile. The occurrence of neonatal thrombocytopenia and bleeding may be a risk factor for subsequent pregnancies. We suggest that the cutoff value for neonatal platelet count for bleeding can be used for management and treatment of neonates born to mothers with ITP.

Juvenile Myelomonocytic Leukemia in Turkey: A Retrospective Analysis of Sixty-five Patients.

OBJECTIVE: This study aimed to define the status of juvenile myelomonocytic leukemia (JMML) patients in Turkey in terms of time of diagnosis, clinical characteristics, mutational studies, clinical course, and treatment strategies. MATERIALS AND METHODS: Data including clinical and laboratory characteristics and treatment strategies of JMML patients were collected retrospectively from pediatric hematology-oncology centers in Turkey. RESULTS: Sixty-five children with JMML diagnosed between 2002 and 2016 in 18 institutions throughout Turkey were enrolled in the study. The median age at diagnosis was 17 months (min-max: 2-117 months). Splenomegaly was present in 92% of patients at the time of diagnosis. The median white blood cell, monocyte, and platelet counts were 32.9x109/L, 5.4x109/L, and 58.3x109/L, respectively. Monosomy 7 was present in 18% of patients. JMML mutational analysis was performed in 32 of 65 patients (49%) and PTPN11 was the most common mutation. Hematopoietic stem cell transplantation (HSCT) could only be performed in 28 patients (44%), the majority being after the year 2012. The most frequent reason for not performing HSCT was the inability to find a suitable donor. The median time from diagnosis to HSCT was 9 months (min-max: 2-63 months). The 5-year cumulative survival rate was 33% and median estimated survival time was 30±17.4 months (95% CI: 0-64.1) for all patients. Survival time was significantly better in the HSCT group (log-rank p=0.019). Older age at diagnosis (>2 years), platelet count of less than 40x109/L, and PTPN11 mutation were the factors significantly associated with shorter survival time. CONCLUSION: Although there has recently been improvement in terms of definitive diagnosis and HSCT in JMML patients, the overall results are not satisfactory and it is necessary to put more effort into this issue in Turkey.

Autosomal recessive osteopetrosis with a unique imaging finding: multiple encephaloceles.

Osteopetrosis is a hereditary form of sclerosing bone dysplasia with various radiological and clinical presentations. The autosomal recessive type, also known as malignant osteopetrosis, is the most severe type, with the early onset of manifestations. A 5-month-old infant was admitted to our hospital with recurrent respiratory tract infections. Chest X-ray and skeletal survey revealed the classic findings of osteopetrosis, including diffuse osteosclerosis and bone within a bone appearance. At follow-up, the patient presented with, thickened calvarium, multiple prominent encephaloceles, and dural calcifications leading to the intracranial clinical manifestations with bilateral hearing and sight loss. Autosomal recessive osteopetrosis is one of the causes of encephaloceles and this finding may become dramatic if untreated.

Marked overlap of four genetic syndromes with dyskeratosis congenita confounds clinical diagnosis.

Dyskeratosis congenita is a highly pleotropic genetic disorder. This heterogeneity can lead to difficulties in making an accurate diagnosis and delays in appropriate management. The aim of this study was to determine the underlying genetic basis in patients presenting with features of dyskeratosis congenita and who were negative for mutations in the classical dyskeratosis congenita genes. By whole exome and targeted sequencing, we identified biallelic variants in genes that are not associated with dyskeratosis congenita in 17 individuals from 12 families. Specifically, these were homozygous variants in USB1 (8 families), homozygous missense variants in GRHL2 (2 families) and identical compound heterozygous variants in LIG4 (2 families). All patients had multiple somatic features of dyskeratosis congenita but not the characteristic short telomeres. Our case series shows that biallelic variants in USB1, LIG4 and GRHL2, the genes mutated in poikiloderma with neutropenia, LIG4/Dubowitz syndrome and the recently recognized ectodermal dysplasia/short stature syndrome, respectively, cause features that overlap with dyskeratosis congenita. Strikingly, these genes also overlap in their biological function with the known dyskeratosis congenita genes that are implicated in telomere maintenance and DNA repair pathways. Collectively, these observations demonstrate the marked overlap of dyskeratosis congenita with four other genetic syndromes, confounding accurate diagnosis and subsequent management. This has important implications for establishing a genetic diagnosis when a new patient presents in the clinic. Patients with clinical features of dyskeratosis congenita need to have genetic analysis of USB1, LIG4 and GRHL2 in addition to the classical dyskeratosis congenita genes and telomere length measurements.

Positive correlation between insulin resistance and iron overload-induced oxidative stress in patients with fanconi anemia (FA)- and non-FA-related bone marrow failure: The results of a multicenter study.

This study investigated the relationship between DNA, protein, and lipid oxidations and insulin resistance in patients with Fanconi anemia (FA)- and non-FA-related bone marrow failure. Sixteen patients with FA, 7 non-FA-related aplastic anemia, and 10 controls were included in the study. Fasting blood glucose, simultaneous insulin, hepcidin, ferritin, 8-hydroxy deoxyguanosine (8-OHdG), protein carbonyls, malondialdehyde (MDA), and homeostatic model assessment-insulin resistance (HOMA-IR) were investigated in the patients and controls. Diepoxybutane test-positive (DEB+) patients were diagnosed with FA, whereas DEB-patients were diagnosed as non-FA. 8-OHdG levels in both FA and non-FA patients were significantly higher than those in the controls (P = .001 and P = .005, respectively). Serum ferritin levels were also higher in FA and non-FA patients than in the controls (P = .0001 and P = .005, respectively). Insulin resistance (IR) was significantly higher in FA patients than in non-FA patients and controls (P = .005 and P = .015, respectively). Significant differences were observed between 8-OHdG, ferritin, and MDA levels in patients with or without IR (P = .009, P = .001, and P = .013, respectively). Moderate and strong relations of 44% and 85% were determined between IR and ferritin levels in patients with FA or non-FA (P = .08 and P = .014, respectively). FA and non-FA patients exhibited a tendency to IR. IR was related to ferritin levels, and ferritin levels were also correlated with oxidative stress. These findings suggest that the increased rate of IR in patients with FA and non-FA may derive from increased oxidative stress, which may in turn be due to elevated serum ferritin levels.

Pancytopenia As the Initial Manifestation of Brucellosis in Children.

Presenting with severe thrombocytopenia and pancytopenia is rare in children with brucellosis, and at the beginning it can be misdiagnosed as a hematological or a viral hemorrhagic disease. The follow-ups of 52 patients diagnosed with brucellosis from January, 2008, to December, 2013, in our clinic have shown the following results. Eleven out of these 52 patients revealed the fact that they had pancytopenia at the admission phase. Anemia and leukopenia were defined as hemoglobin levels and leukocyte counts below the standard values in terms of ages, thrombocytopenia as thrombocyte counts below 150,000/mm(3), and severe thrombocytopenia as thrombocyte counts below 20,000/mm(3). The most frequent admission symptoms and findings of the patients with pancytopenia were fever (75%), fatigue (50%), splenomegaly (75%), and hepatomegaly (41%). Laboratory results were hemoglobin 9.3±0.96 gram/dL, white blood cell count 2226±735.9/mm(3), and thrombocyte count 70,090±47,961/mm(3). The standard tube agglutination test was positive for all patients, and Brucellosis spp. were isolated in the blood cultures of six (54%) patients. Three of the 11 patients had severe thrombocytopenia, and they were admitted with complaints of epistaxis, gingival bleeding, petechiae, and purpura. At the beginning, two of three cases were misdiagnosed as Crimean-Congo hemorrhagic fever (CCHF), another zoonotic endemic disease in Turkey. Pancytopenia improved with treatment of brucellosis on all patients. In conclusion, brucellosis can show great similarity with hematologic and zoonotic diseases like CCHF. Brucellosis should be considered in the differential diagnosis of pancytopenia, treatment-resistant immune thrombocytopenia, and viral hemorrhagic disease, especially in countries where brucellosis is endemic.

Platelet collection efficiencies of three different platelet-rich plasma preparation systems.

BACKGROUND: Different systems have been used for the preparation of platelet-rich plasma (PRP), but platelet collection efficiencies of these systems are not clear. OBJECTIVE: To evaluate the platelet collection efficiencies of three different PRP preparation systems. MATERIALS AND METHODS: Blood samples were obtained from the same 16 volunteers for each system. The samples were centrifuged and PRP was prepared by three systems. The ratio of the total number of platelets in PRP to the total number of platelets of the venous blood sample of the patient expressed in percentage was named as platelet collection efficiency and calculated for each system. RESULTS: Mean platelet collection efficiencies were 66.6 (min: 56.9, max: 76.9), 58.3 (min: 27.3, max: 102.8), 50.8 (min: 27.2, max: 73) for top and bottom bag system, system using citrated tube, and the system using tube with Ficoll and cell extraction kit, respectively. Statistically significant difference was found only between the platelet collection efficiencies of systems using the tube with ficoll and cell extraction kit and the top and bottom bag system (p = 0.002). CONCLUSIONS: All three systems could be used for PRP preparation, but top and bottom bag system offers a slight advantage over the system using Ficoll and cell extraction kit regarding the platelet collection efficiency.

Invasive fungal infections in children with hematologic and malignant diseases.

BACKGROUND: To evaluate the clinical feature and outcome of invasive fungal infections (IFI) in children with hematologic and malign diseases. PATIENTS AND METHODS: The medical records of children with hematologic and malignant diseases, who were hospitalized at our hospital between January 2010 and December 2011, were reviewed. Proven, probable, and possible IFIs were diagnosed according to the revised definitions of the European Organization for Research and Treatment of Cancer/Mycosis Study Group. The demographic, clinical, and laboratory characteristics of the patients who met the study criteria were evaluated. RESULTS: IFI was diagnosed in 67 (7.2%) febrile episodes of 56 patients, of which 10 (1.2%) were proven, 20 (2%) probable, and 37 (4%) possible IFI. Blood culture of 10 cases with proven IFI yielded yeast and the most common isolated agent was Candida parapsilosis. Seventy percent of cases with fungemia had central venous catheter (CVC). Twenty cases with probable IFI had invasive mold infection. The cases with mold infection had higher median C-reactive protein values, lower neutrophil counts, and longer duration of neutropenia compared with the cases with yeast infection. A total of 14 patients (20.9%) died. Presence of CVC, bone marrow transplantation, total parenteral nutrition, prolonged fever, and proven/probable IFI were detected more often in patients who died, compared with patients who survived. CONCLUSIONS: IFIs are important causes of death in children with hematologic and malignant diseases. Mold infections are seen more frequently in cases with prolonged and profound neutropenia, and invasive yeast infections, especially with non-albicans Candida species, in cases with CVC. Early and effective treatment considering these findings will help to decrease the mortality.

Red cell glucose 6-phosphate dehydrogenase deficiency in the northern region of Turkey: is G6PD deficiency exclusively a male disease?

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked recessive genetic defect that can cause hemolytic crisis. However, this disease affects both males and females. In Turkey, the frequency of this enzyme deficiency was reported to vary, from 0.25 to 18%, by the geographical area. Its prevalence in the northern Black Sea region of Turkey is unknown. The aims of this study were to assess the prevalence of G6PD deficiency in the northern region Turkey in children and adults with hyperbilirubinemia and hemolytic anemia. This report included a total of 976 G6PD enzyme results that were analyzed between May 2005 and January 2014. G6PD deficiency was detected in 5.0% of all patients. G6PD deficiency was significantly less frequent in females (1.9%, 6/323) than in males (6.6%, 43/653). G6PD deficiency was detected in 3.7% of infants with hyperbilirubinemia, 9.2% of children, and 4.5% of adults with hemolytic anemia. In both the newborn group and the group of children, G6PD deficiency was significantly more frequent in males. In the combined group of children (groups I and II), the proportion of males was 74% and 67% in all groups (P = .0008). In conclusion, in northern region of Turkey, G6PD deficiency is an important cause of neonatal hyperbilirubinemia and hemolytic crisis in children and adults. This study suggests that most pediatricians thought that G6PD deficiency is exclusively a male disease. For this reason, some female patients may have been undiagnosed.

Vitamin D levels in children with severe hemophilia A: an underappreciated deficiency.

Osteoporosis in hemophilic patients is a significant problem. The causes of osteoporosis in hemophilic patients are lack of adequate exercise, multiple hemorrhage and inflammation, and low vitamin D levels. The aim of this study was to retrospectively determine the frequency of vitamin D deficiency and insufficiency in children with severe hemophilia A. Forty-seven children with severe hemophilia were included in the study. None of the patients had previously received vitamin D supplementation. No patient had clinical or radiologic findings of rickets or seropositivity of hepatitis C virus or HIV. The mean age of the patients was 11.64 ±â€Š5.70 (range, 2-18) years. The mean vitamin D level was 16.35 ±â€Š7.49 ng/ml (range, 3.25-33.80). Vitamin D levels were below 10 ng/ml (severe vitamin D deficiency) in 9 cases (19%), between 10 and 19.99 ng/ml (vitamin D deficiency) in 23 cases (49%), between 20 and 29.99 ng/ml (vitamin D insufficiency) in 13 cases (28%), and above 30 ng/ml (normal vitamin D level) in 2 cases (4%). The mean serum levels of 25-hydroxy vitamin D in the children with hemophilia during winter and autumn were significantly lower than that during summer (P = 0.0028 and P = 0.0091, respectively). A majority of our hemophilic patients (96%) had low vitamin D levels. The study showed that the risk of vitamin D deficiency is the most highest during winter and autumn. Normal lifelong vitamin D levels are especially important in hemophilia because of the possible synergistic effect of vitamin D levels on periarticular and general osteoporosis, which is intrinsic to hemophilic conditions. We advise routine checking of vitamin D levels twice a year and vitamin D supplementation to maintain its level between 30 and 100 ng/ml.