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Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.
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Anemia Hemolítica Congénita no Esferocítica , Intrones , Piruvato Quinasa , Errores Innatos del Metabolismo del Piruvato , Humanos , Piruvato Quinasa/deficiencia , Piruvato Quinasa/genética , Masculino , Femenino , Errores Innatos del Metabolismo del Piruvato/genética , Niño , Preescolar , Anemia Hemolítica Congénita no Esferocítica/genética , Turquía , Lactante , Adolescente , MutaciónRESUMEN
Intellectual disability is characterized by impairment in at least two of the following areas: social skills, communication skills, self-care tasks, and academic skills. These impairments are evaluated in relation to the expected standards based on the individual's age and cultural levels. Additionally, intellectual disability is typically defined by a measurable level of intellectual functioning, represented by an intelligence quotients core of 70 or below. Autism spectrum disorder is a developmental disability resulting from differences in the brain, often characterized by problems in social communication and interaction, and limited or repetitive behaviors or interests. Hereditary spherocytosis is a disease characterized by anemia, jaundice, and splenomegaly as a result of increased tendency to hemolysis with morphological transformation of erythrocytes from biconcave disc-shaped cells with central pallor to spherocytes lacking central pallor due to hereditary injury of cellular membrane proteins. An 11-year-old female patient was referred to Pediatric Genetics Subdivision due to the presence of growth retardation and a diagnosis of hereditary spherocytosis. Since she also had dysmorphic facial features, such as frontal bossing, broad and prominent forehead, tubular nasal structure, and thin vermillion, genetic tests were performed. Chromosomal microarray analysis revealed a 2.5â Mb deletion in the 14q23.2q23.3 region. Deletion was also identified in the same region in her father, who had the same phenotypic characteristics, including hereditary spherocytosis and learning difficulties. We propose that the PLEKHG3 and AKAP5 genes, which are located in this region, may contribute to the development of intellectual disability.
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Deleción Cromosómica , Haploinsuficiencia , Discapacidad Intelectual , Humanos , Discapacidad Intelectual/genética , Femenino , Niño , Haploinsuficiencia/genética , Proteínas de Anclaje a la Quinasa A/genética , Esferocitosis Hereditaria/genéticaRESUMEN
Severe combined immunodeficiency (SCID) is an inborn errors of immunity (IEI) disorder characterized by impairment in the development and function of lymphocytes and could be fatal if not treated with hematopoietic stem cell transplant in the first 2 years of life. There are various diagnostic criteria for SCID among different primary immunodeficiency societies. We retrospectively evaluated clinical and laboratory findings of 59 patients followed up with the diagnosis of SCID at our clinic over the past 20 years in order to develop an algorithm that would help diagnosis of SCID for the countries where a high ratio of consanguineous marriage is present because these countries have not launched TREC assay in their newborn screening programs. The mean age at diagnosis was 5.80 ± 4.90 months, and the delay was 3.29 ± 3.99 months. The most common complaint and physical examination findings were cough (29.05%), eczematous rash (63%) and organomegaly (61%). ADA (17%), Artemis (14%), RAG1/2 (15%), MHC Class II (12%) and IL-2R (12%) deficiencies were the most common genetic defects. Lymphopenia (87.5%) was the most frequent abnormal laboratory finding and below 3000/mm3 in 95% of the patients. The CD3+ T cell count was 300/mm3 and below in 83% of the patients. As a result, a combination of low lymphocyte count and CD3 lymphopenia for SCID diagnosis would be more reliable for countries with high rate of consanguineous marriage. Physicians should consider diagnosis of SCID in a patient presenting with severe infections and lymphocyte counts below 3000/mm3 under 2 years of age.
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Linfopenia , Inmunodeficiencia Combinada Grave , Recién Nacido , Humanos , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/genética , Estudios Retrospectivos , Linfopenia/diagnóstico , Linfopenia/genética , Linfocitos , Genes MHC Clase IIRESUMEN
BACKGROUND: In patients with acute lymphoblastic leukemia (ALL), the risk of thromboembolism increases due to hemostatic changes secondary to the primary disease and due to treatment-related factors. In this multicenter study, we aimed to research the frequency of central nervous system (CNS) thrombosis occurring during treatment, hereditary and acquired risk factors, clinical and laboratory features of patients with thrombosis, treatment approaches, and thrombosis-related mortality and morbidity rates in pediatric ALL patients. PROCEDURE: Pediatric patients who developed CNS thrombosis during ALL treatment from 2010 to 2021 were analyzed retrospectively in 25 different Pediatric Hematology Oncology centers in Türkiye. The demographic characteristics of the patients, symptoms associated with thrombosis, the stage of the leukemia treatment during thrombosis, the anticoagulant therapy applied for thrombosis, and the final status of the patients recorded through electronic medical records were determined. RESULTS: Data from 70 patients with CNS thrombosis during treatment, out of 3968 pediatric patients with ALL, were reviewed. The incidence of CNS thrombosis was 1.8% (venous: 1.5 %; arterial: 0.03%). Among patients with CNS thrombosis, 47 had the event in the first 2 months. Low molecular weight heparin (LMWH) was the most commonly used treatment with a median of 6 months (min-max: 3-28 months). No treatment-related complications occurred. Chronic thrombosis findings occurred in four patients (6%). In five (7%) patients who developed cerebral vein thrombosis, neurological sequelae (epilepsy and neurological deficit) remained. One patient died related to thrombosis, and the mortality rate was 1.4%. CONCLUSION: Cerebral venous thrombosis and, less frequently, cerebral arterial thrombosis may develop in patients with ALL. The incidence of CNS thrombosis is higher during induction therapy than during other courses of treatment. Therefore, patients receiving induction therapy should be monitored carefully for clinical findings suggestive of CNS thrombosis.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Trombosis , Humanos , Niño , Heparina de Bajo-Peso-Molecular/uso terapéutico , Estudios Retrospectivos , Turquía/epidemiología , Trombosis/epidemiología , Trombosis/etiología , Leucemia-Linfoma Linfoblástico de Células Precursoras/complicaciones , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamiento farmacológico , Sistema Nervioso CentralRESUMEN
Inborn errors of IFN-γ immunity can underlie tuberculosis (TB). We report three patients from two kindreds without EBV viremia or disease but with severe TB and inherited complete ITK deficiency, a condition associated with severe EBV disease that renders immunological studies challenging. They have CD4+ αß T lymphocytopenia with a concomitant expansion of CD4-CD8- double-negative (DN) αß and Vδ2- γδ T lymphocytes, both displaying a unique CD38+CD45RA+T-bet+EOMES- phenotype. Itk-deficient mice recapitulated an expansion of the γδ T and DN αß T lymphocyte populations in the thymus and spleen, respectively. Moreover, the patients' T lymphocytes secrete small amounts of IFN-γ in response to TCR crosslinking, mitogens, or forced synapse formation with autologous B lymphocytes. Finally, the patients' total lymphocytes secrete small amounts of IFN-γ, and CD4+, CD8+, DN αß T, Vδ2+ γδ T, and MAIT cells display impaired IFN-γ production in response to BCG. Inherited ITK deficiency undermines the development and function of various IFN-γ-producing T cell subsets, thereby underlying TB.
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Receptores de Antígenos de Linfocitos T gamma-delta , Tuberculosis , Animales , Humanos , Ratones , Interferón gamma , Receptores de Antígenos de Linfocitos T alfa-beta/genética , Receptores de Antígenos de Linfocitos T gamma-delta/genética , Subgrupos de Linfocitos T , TimoRESUMEN
BACKGROUND: Cystic fibrosis (CF) is a multisystemic, autosomal recessive disease, which is caused by a mutation in the transmembrane conduction regulator protein (CFTR) gene. We present a patient who was diagnosed with CF and later diagnosed with Niemann-Pick type-A (NPA) disease, which is an autosomal recessive lysosomal lipid storage disease. CASE: A 2-month-old Syrian refugee patient was diagnosed with CF due to a high sweat test and two homozygous CFTR-related pathogenic gene mutations in our pediatric pulmonology clinic, where she was referred due to a high immunoreactive trypsinogen (IRT) value as a result of newborn screening. As the patient had neurological symptoms and hepatosplenomegaly that could not be explained by CF in the clinical follow-up, the patient was diagnosed with NPA was made with a cherry red spot on eye examination, foam cells in the bone marrow, and low sphingomyelinase activity, in addition to CF. CONCLUSIONS: Although CF and NP have common systems of involvement in both diseases, pathological symptoms have different origins. If a patient with CF has simultaneous neuromotor delay, other autosomal recessive diseases that may accompany it should be suspected. In studies, similar pathological pathways related to abnormal cholesterol accumulation in the cell were detected between NP type C and CF. But our case was NPA. As case reports on the coexistence of the two diseases increase, we believe that a better understanding of similar pathological pathways may lead to new therapeutic targets for both diseases.
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Fibrosis Quística , Enfermedades de Niemann-Pick , Recién Nacido , Niño , Femenino , Humanos , Lactante , Fibrosis Quística/complicaciones , Fibrosis Quística/diagnóstico , Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Pruebas Genéticas , Enfermedades Raras/genética , Tamizaje Neonatal , Mutación , Enfermedades de Niemann-Pick/genéticaRESUMEN
Background: Pulmonary embolism is a clinical condition caused by the obstruction of the pulmonary artery and its branches with endogenous, exogenous embolism, or local thrombus formation. It is a rare but potentially life-threatening event in the pediatric population. Pediatric pulmonary embolism has many unknown characteristics. Aims: To evaluate clinical features, genetic and acquired risk factors, diagnostic imaging, and treatment strategies with long-term results in children with pulmonary embolism. Study Design: A retrospective multicenter clinical trial. Methods: Patients aged 0-18 years who were diagnosed with pulmonary embolism with computed tomography pulmonary angiography (CTPA) findings (intraluminal filling defect in the lobar or main pulmonary artery) in 3 university hospitals between 2006 and 2021 were included in the study. A form was created for data standardization, and variables were collected retrospectively through medical record review. In addition to the features given above, we also evaluated in situ pulmonary artery thrombosis (ISPAT) and patients' Wells scores. Follow-up CTPA results were evaluated for patient response to treatment. Complete recovery means that there were no lesions, incomplete recovery if there was still embolism, and no response if there was no change. Results: Twenty-four patients (female:13, male:11) were included in the study. The mean age was 13.5 years. All patients but one had at least one or more genetic or acquired risk factors. Factor V Leiden mutation (16.6%) was the most common genetic risk factor. Six of 16 patients with Doppler ultrasonography were diagnosed with ISPAT because there was no sign of thromboembolic thrombosis. Nine (41.6%) patients had a Wells score of >4 (pulmonary embolism clinically strong), and 15 (58.4%) patients scored <4 (pulmonary embolism clinically likely weak), indicating that an alternative diagnosis was more likely than pulmonary embolism (sensitivity %37.5). The mean follow-up period was 23 (±17) months. Complete and incomplete recovery was observed in 15 (62.5%) and 7 (29.1%) patients, respectively, among the patients who underwent follow-up evaluation. No response was obtained in 2 patients (8.3%) who died. Conclusion: The Wells scoring system seems insufficient to diagnose pulmonary embolism in children and should be improved by adding new parameters. ISPAT may be more common in children with congenital heart disease and systemic disease.
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Embolia Pulmonar , Adolescente , Angiografía/métodos , Niño , Angiografía por Tomografía Computarizada , Femenino , Humanos , Masculino , Embolia Pulmonar/diagnóstico , Embolia Pulmonar/etiología , Estudios Retrospectivos , Turquía/epidemiologíaRESUMEN
BACKGROUND: Central nervous system fungal infections (CNSFI) are seen in patients with hematologic malignancies and have high morbidity and mortality. Because of their rarity, there is limited data on CNSFI in children with no established treatment protocols or guidelines. MATERIALS AND METHODS: In this multicenter retrospective study, 51 pediatric patients with leukemia, 6 of whom had undergone bone marrow transplantation, with proven or probable CNSFI were evaluated. Fungal infections were defined as proven or probable based on European Organisation for Research and Treatment of Cancer criteria. Proven CNSFI was diagnosed by appropriate central nervous system (CNS) imaging or tissue sample findings in combination with positive microbiological results of cerebrospinal fluid. A positive culture, microscopic evidence of hyphae, a positive result of the galactomannan assays are defined as positive microbiological evidence. Probable CNSFI was defined as appropriate CNS imaging findings together with proven or probable invasive fungal infections at another focus without CNS when there is no other explanatory condition. Data was collected by using the questionnaire form (Supplemental Digital Content 1, http://links.lww.com/JPHO/A541 ). RESULTS: Seventeen patients had proven, 34 patients had probable CNSFI. Headaches and seizures were the most common clinical findings. The median time between the onset of fever and diagnosis was 5 days. The most common fungal agent identified was Aspergillus . Sixteen patients received single-agent, 35 received combination antifungal therapy. Surgery was performed in 23 patients. Twenty-two patients (43%) died, 29 of the CNSFI episodes recovered with a 20% neurological sequelae. CONCLUSION: CNSFIs should be considered in the differential diagnosis in patients with leukemia and refractory/recurrent fever, headache, neurologicalocular symptoms, and a radiologic-serological evaluation should be performed immediately. Early diagnosis and prompt management, both medical and surgical, are essential for improving clinical outcomes.
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Infecciones Fúngicas del Sistema Nervioso Central , Trasplante de Células Madre Hematopoyéticas , Infecciones Fúngicas Invasoras , Leucemia , Niño , Humanos , Estudios Retrospectivos , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Infecciones Fúngicas Invasoras/diagnóstico , Infecciones Fúngicas Invasoras/tratamiento farmacológico , Infecciones Fúngicas Invasoras/etiología , Infecciones Fúngicas del Sistema Nervioso Central/diagnóstico , Infecciones Fúngicas del Sistema Nervioso Central/terapia , Antifúngicos/uso terapéutico , Leucemia/tratamiento farmacológicoRESUMEN
BACKGROUND: With more than 3.6 million Syrian refugees Turkey hosts the world's largest number of Syrians. Considering the morbidity, mortality, and healthcare spending, cancer is one of the leading health and economic burden for patients and healthcare systems. However, very limited information available in the scientific literature to understand the burden and characteristics of cancer in countries hosting Syrian refugees. The aim of the present study is to evaluate the demographic and clinical characteristics, treatment outcome of Syrian cancer patients living in Konya, Turkey. METHODS: We retrospectively reviewed medical records of Syrian cancer patients at three major institutions from 2005 to 2020. The information regarding demographic and clinical characteristics of patients were identified. The number of days between the first symptom and diagnosis was considered as the "diagnostic interval". Patients who failed to attend clinics within four weeks of appointment were assumed abandoned treatment. Survival curves were estimated using the Kaplan-Meier method. RESULTS: We identified 230 adult and 38 children refugee diagnosed with cancer during the study period. With regards to adult patients, there were 114 (49.6%) male and 116 (50.4%) female. The median age at diagnosis was 52.4, 47.3 years for male, female respectively. The five most common cancer by site among all were; breast (24.8%), colorectal (10.9%), lung (7.4%), central nervous system (CNS) (7.0%), and stomach (5.2%). 93 (40.4%) had metastatic disease at diagnosis. The overall survival probability was 37.5% at five years for the adult population. Data were extracted for 20 boys and 18 girls with childhood cancer. Their median age at diagnosis was 5.8 and 6.0 years respectively. The three most common childhood cancer were; leukemias (21.1%), lymphomas (21.1%), and CNS (13.2%). Excluding leukemia, 13 (43.3%) of childhood cancer cases had the advanced disease at diagnosis. Three year survival probality was 69.5%. The median diagnostic interval for adult and childhood cancer was 96.5 (IQR = 53-165) and 23 (IQR = 13.5-59) days respectively. Twenty-one adults and four children had treatment abandonment. CONCLUSION: This study contributes to understanding the burden of cancer among Syrian refugees living in Konya, growing health issue for refugees. Larger and prospective studies will help to measure the real burden and compare the difference in cancer risk factors, care, and outcomes among the refugee and host populations.
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Objective: This study aimed to observe the preventive effect of prophylactic treatment on joint health in people with hemophilia (PwH) and to investigate the importance of integration of ultrasonographic examination into clinical and radiological evaluation of the joints. Materials and Methods: This national, multicenter, prospective, observational study included male patients aged ≥6 years with the diagnosis of moderate or severe hemophilia A or B from 8 centers across Turkey between January 2017 and March 2019. Patients were followed for 1 year with 5 visits (baseline and 3th, 6th, 9th, and 12th month visits). The Hemophilia Joint Health Score (HJHS) was used for physical examination of joints, the Pettersson scoring system was used for radiological assessment, point-of-care (POC) ultrasonography was used for bilateral examinations of joints, and the Hemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score was used for evaluation of ultrasonography results. Results: Seventy-three PwH, of whom 62 had hemophilia A and 11 had hemophilia B, were included and 24.7% had target joints at baseline. The HJHS and HEAD-US scores were significantly increased at the 12th month in all patients. These scores were also higher in the hemophilia A subgroup than the hemophilia B subgroup. However, in the childhood group, the increment of scores was not significant. The HEAD-US total score was significantly correlated with both the HJHS total score and Pettersson total score at baseline and at the 12th month. Conclusion: The HEAD-US and HJHS scoring systems are valuable tools during follow-up examinations of PwH and they complement each other. We suggest that POC ultrasonographic evaluation and the HEAD-US scoring system may be integrated into differential diagnosis of bleeding and long-term monitoring for joint health as a routine procedure.
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Hemofilia A/prevención & control , Artropatías/diagnóstico , Proyectos de Investigación/estadística & datos numéricos , Ultrasonografía/métodos , Adolescente , Adulto , Anciano , Niño , Diagnóstico Diferencial , Diagnóstico Precoz , Estudios de Seguimiento , Hemofilia A/diagnóstico , Hemofilia A/terapia , Hemorragia/diagnóstico , Hemorragia/etiología , Humanos , Artropatías/prevención & control , Articulaciones/diagnóstico por imagen , Articulaciones/patología , Masculino , Persona de Mediana Edad , Pruebas en el Punto de Atención , Estudios Prospectivos , Factores Protectores , Proyectos de Investigación/tendencias , Índice de Severidad de la Enfermedad , Turquía/epidemiologíaRESUMEN
In this study, the clinical and laboratory findings, management and follow-up of 32 children with paediatric systemic lupus erythematosus (pSLE) were evaluated to determine the prognostic factors in pSLE. Of the 32 patients, 25 (78.1%) were females. Age at onset of symptoms and diagnosis in the patients were 147.6 ± 49 months and 154.3 ± 48 months, respectively. The most common symptom on admission were joint problems, seen in 25 (78.1%) patients. Haematological alterations were seen in 25 (78.1%) cases during follow-up. Lupus nephritis was diagnosed in 10 (31.2%) patients. Malar rash was seen in a total of 12 (37.5%) patients during follow up, however it had been noted in five (15.6%) patients on admission. Antinuclear antibody and anti-dsDNA were positive in all patients and 31 (96.8%) patients, respectively. Decreased complement 3 and 4 levels were noted in 23 (71.8%) patients. Antiphospholipid antibody was studied in 27 patients and it was found to be positive in 13 (48.1%) patients. In conclusion, based on our findings, we would like to emphasize that pSLE has a large and remarkable clinical and laboratory findings.
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Lupus Eritematoso Sistémico , Nefritis Lúpica , Edad de Inicio , Anticuerpos Antinucleares , Niño , Femenino , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Lupus Eritematoso Sistémico/epidemiología , Masculino , Derivación y ConsultaRESUMEN
PURPOSE: To describe a case of traumatic hyphema in a patient with severe hemophilia A. CASE: We present a case of a 16-year-old boy with severe hemophilia A who presented to our ophthalmology department with total hyphema and elevated intraocular pressure 3 days after a history of blunt ocular trauma on his right eye. Due to the persistent intraocular pressure elevation and total hyphema despite medical intervention, an early anterior chamber washout was performed with the replacement of factor VIII preoperatively and postoperatively. Re-bleeding or any other complications were not experienced during surgery or postoperatively. At the first postoperative week, 20/20 visual acuity and a normal intraocular pressure without antiglaucoma medication was retained and remained stable during the 6-month follow-up. CONCLUSION: In such cases with hemophilia A, traumatic hyphema, and intraocular pressure elevation despite medical intervention, an early surgical clot removal under intense factor VIII replacement could be performed. In the early postoperative period, factor replacement should be resumed in order to avoid re-bleeding.
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Lesiones Oculares/diagnóstico , Hemofilia A/complicaciones , Hipema/diagnóstico , Hipema/tratamiento farmacológico , Heridas no Penetrantes/diagnóstico , Adolescente , Cámara Anterior/efectos de los fármacos , Coagulantes/uso terapéutico , Lesiones Oculares/tratamiento farmacológico , Lesiones Oculares/etiología , Factor VIII/uso terapéutico , Hemofilia A/tratamiento farmacológico , Humanos , Hipema/etiología , Presión Intraocular , Masculino , Agudeza Visual , Heridas no Penetrantes/tratamiento farmacológico , Heridas no Penetrantes/etiologíaRESUMEN
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.
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Anemia Ferropénica/tratamiento farmacológico , Benzoatos/uso terapéutico , Hidrazinas/uso terapéutico , Púrpura Trombocitopénica Idiopática/tratamiento farmacológico , Pirazoles/uso terapéutico , Administración Oral , Adolescente , Anemia Ferropénica/diagnóstico , Benzoatos/administración & dosificación , Benzoatos/efectos adversos , Niño , Preescolar , Femenino , Humanos , Hidrazinas/administración & dosificación , Hidrazinas/efectos adversos , Lactante , Masculino , Púrpura Trombocitopénica Idiopática/diagnóstico , Pirazoles/administración & dosificación , Pirazoles/efectos adversos , Estudios Retrospectivos , Resultado del Tratamiento , TurquíaRESUMEN
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.
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Proteínas Adaptadoras Transductoras de Señales/genética , Síndromes Congénitos de Insuficiencia de la Médula Ósea/genética , Neutropenia/genética , Adolescente , Adulto , Niño , Preescolar , Consanguinidad , Análisis Mutacional de ADN , Femenino , Homocigoto , Humanos , Lactante , Masculino , Mutación , Sistema de Registros , Turquía , Adulto JovenRESUMEN
INTRODUCTION: Glanzmann thrombasthenia is a rare congenital platelet dysfunction. CASE CHARACTERISTICS: A 2-day-old male neonate delivered at 35 weeks' gestation was referred with extensive bruising and jaundice. His elder sibling had Glanzmann thrombasthenia, and his mother had thrombophilic risk factors. Flow cytometric analysis revealed absent CD41/CD61. A molecular thrombophilia panel revealed the presence of heterozygous factor V Leiden G1691A and methylenetetrahydrofolate reductase C677T gene mutations. OUTCOME: General precautions to avoid injuries and spontaneous bleeding were advised. MESSAGE: Life-threatening bleeding may not be the first finding in cases of thrombasthenia accompanied by thrombophilic risk factors.
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Trombastenia , Adulto , Factor V/genética , Femenino , Humanos , Recién Nacido , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Embarazo , Trombastenia/diagnóstico , Trombastenia/genéticaRESUMEN
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.
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Talasemia/epidemiología , Distribución por Edad , Alelos , Demografía , Femenino , Humanos , Masculino , Tamizaje Masivo , Mutación , Fenotipo , Vigilancia de la Población , Sistema de Registros , Talasemia/diagnóstico , Talasemia/prevención & control , Talasemia/terapia , Turquía/epidemiologíaRESUMEN
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.
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Leucemia Mielomonocítica Juvenil/epidemiología , Biopsia , Preescolar , Terapia Combinada , Femenino , Pruebas Genéticas , Humanos , Lactante , Leucemia Mielomonocítica Juvenil/diagnóstico , Leucemia Mielomonocítica Juvenil/etiología , Leucemia Mielomonocítica Juvenil/terapia , Masculino , Vigilancia en Salud Pública , Estudios Retrospectivos , Análisis de Supervivencia , Evaluación de Síntomas , Turquía/epidemiologíaRESUMEN
Chediak-Higashi syndrome (CHS) is caused by autosomal recessive mutations in LYST, resulting in enlarged lysosomal compartments in multiple cell types. CHS patients display oculocutaneous albinism and may develop life-threatening hemophagocytic lymphohistiocytosis (HLH). While NK cell-mediated cytotoxicity has been reported to be uniformly defective, variable defects in T cell-mediated cytotoxicity has been observed. The latter has been linked to the degree of HLH susceptibility. Since the discrepancies in NK cell- and T cell-mediated cellular cytotoxicity might result from differences in regulation of cytotoxic granule release, we here evaluated perforin-containing secretory lysosome size and number in freshly isolated lymphocytes from CHS patients and furthermore compared their exocytic capacities. Whereas NK cells from CHS patients generally contained a single, gigantic perforin-containing granule, cytotoxic T cells predominantly contained several smaller granules. Nonetheless, in a cohort of 21 CHS patients, cytotoxic T cell and NK cell granule exocytosis were similarly impaired upon activating receptor stimulation. Mechanistically, polarization of cytotoxic granules was defective in cytotoxic lymphocytes from CHS patients, with EEA1, a marker of early endosomes, mislocalizing to lysosomal structures. The results leads to the conclusion that lysosome enlargement corresponds to loss of distinct organelle identity in the endocytic pathway, which on a subcellular level more adversely affects NK cells than T cells. Hence, vesicular size or numbers do not per se dictate the impairment of lysosomal exocytosis in the two cell types studied.
RESUMEN
PURPOSE: To determine the prevalence and the pattern of ocular involvement in children with leukemia at the time of diagnosis. METHODS: The data of patients with leukemia who underwent complete ophthalmic examination at the time of diagnosis between January 2005 and December 2014 were retrospectively reviewed. Demographic data, type of leukemia, ocular findings, blood parameters, and duration of follow-up were analyzed. RESULTS: A total of 185 patients (111 male and 74 female) were included in the study, with a median age of 6.0 years (range 0.5-18.0 years) and a median follow-up time of 36.0 months (range 0.5-108.0 months). Ocular signs were present in 24.3% of the patients at the time of diagnosis and 37.8% of them were symptomatic. The prevalence of ocular involvement was 20.4% in patients with acute lymphocytic leukemia (ALL) and 36.4% in patients with acute myelocytic leukemia (AML) (p = 0.051). Fatality rate was significantly higher in subjects with AML compared with ALL (p = 0.019), but was not significantly different between patients with and without ocular involvement (p = 0.166). There were no significant differences in hemoglobin levels, white blood cell counts, or platelet counts between patients with ALL and AML. Platelet counts were significantly lower in patients with ocular signs compared with subjects without ocular involvement (p = 0.012), while hemoglobin levels and white blood cell counts did not differ significantly. CONCLUSIONS: Various ocular signs may be present at the time of diagnosis in childhood leukemia, even in patients without any symptoms. Routine ophthalmic examination should be performed in recently diagnosed children with leukemia.