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.

Low Density Granulocytes and Dysregulated Neutrophils Driving Autoinflammatory Manifestations in NEMO Deficiency.

NF-κB essential modulator (NEMO, IKK-γ) deficiency is a rare combined immunodeficiency caused by mutations in the IKBKG gene. Conventionally, patients are afflicted with life threatening recurrent microbial infections. Paradoxically, the spectrum of clinical manifestations includes severe inflammatory disorders. The mechanisms leading to autoinflammation in NEMO deficiency are currently unknown. Herein, we sought to investigate the underlying mechanisms of clinical autoinflammatory manifestations in a 12-years old male NEMO deficiency (EDA-ID, OMIM #300,291) patient by comparing the immune profile of the patient before and after hematopoietic stem cell transplantation (HSCT). Response to NF-kB activators were measured by cytokine ELISA. Neutrophil and low-density granulocyte (LDG) populations were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMC) transcriptome before and after HSCT and transcriptome of sorted normal-density neutrophils and LDGs were determined using the NanoString nCounter gene expression panels. ISG15 expression and protein ISGylation was based on Immunoblotting. Consistent with the immune deficiency, PBMCs of the patient were unresponsive to toll-like and T cell receptor-activators. Paradoxically, LDGs comprised 35% of patient PBMCs and elevated expression of genes such as MMP9, LTF, and LCN2 in the granulocytic lineage, high levels of IP-10 in the patient's plasma, spontaneous ISG15 expression and protein ISGylation indicative of a spontaneous type I interferon (IFN) signature were observed, all of which normalized after HSCT. Collectively, our results suggest that type I IFN signature observed in the patient, dysregulated LDGs and spontaneously activated neutrophils, potentially contribute to tissue damage in NEMO deficiency.

Knowing the ABCs: teaching the principles of radiology to medical students in Turkey.

BACKGROUND: Radiology education in Turkey is mainly taught during clinical years of medical school and often lacks main principles. Exposure to the fundamentals of radiology at an early stage of medical education may drastically help students generate a better understanding of radiology and expand their interest in the specialty. With the Principles of Radiology Course that we provided, pre- and post-session tests, and assessment survey at the end of the course, we aimed to evaluate the effectiveness of such an online course among Turkish medical students. METHODS: A total of nine online sessions on imaging modalities principles was developed by radiology professors. Each session was given through Zoom by radiologists from different U.S.-institutions to Turkish medical students from state (n = 33) and private (n = 8) universities. Pretests and post-tests were given to participants via Qualtrics before and after each session, respectively. Paired two-sample t-tests were conducted to detect the variance and p=-.05 was used as the significance level. An evaluation survey was distributed at the end of the course to collect their feedback through SurveyMonkey. RESULTS: A total of 1,438 predominantly Turkish (99.32%) medical students engaged with this course. An average of 506 students completed both pre-test and post-test. There was a statistically significant (p < .001) increase in the scores in post-test (mean[range]:7.58[5.21-8.53]) relative to pre-test (mean[range]:5.10[3.52-8.53]). Four hundred and thirty-nine participants (F/M:63.33%/35.54%) completed the end-of-course survey. A total of 71% and 69.70% of the participants strongly agreed that the course would be useful in their clinical practice and had increased their understanding of radiology. They also reported that their level of confidence in the subjects had increased 68% and reached a weighted average of 3.09/4. The survey revealed that 396 (90.21%) of the participants strongly or somewhat agree that introductory principles and concepts should be presented in earlier years of medical education. Compared to in-person education, 358 (81.55%) found the course extremely or very convenient. CONCLUSION: Online lecture series consisting of the principles of the radiological imaging modalities can be offered to Turkish medical students to enhance their grasp of the various imaging modalities and their correct clinical application.

Malignancy and lymphoid proliferation in primary immune deficiencies; hard to define, hard to treat.

BACKGROUND: Regarding the difficulties in recognition and management of the malignancies in primary immune deficiencies (PIDs), we aimed to present the types, risk factors, treatment options, and prognosis of the cancers in this specific group. METHODS: Seventeen patients with PID who developed malignancies or malignant-like diseases were evaluated for demographics, clinical features, treatment, toxicity, and prognosis. RESULTS: The median age of malignancy was 12.2 years (range, 2.2-26). Lymphoma was the most frequent malignancy (n = 7), followed by adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), cholangiocarcinoma (n = 1), Wilms tumor (n = 1), and acute myeloid leukemia (n = 1). Nonneoplastic lymphoproliferation mimicking lymphoma was observed in five patients. The total overall survival (OS) was 62.5% ± 12.1%. The OS for lymphoma was 62.2% ± 17.1% and found to be inferior to non-PID patients with lymphoma (P = 0.001). CONCLUSION: In patients with PIDs, malignancy may occur and negatively affect the OS. The diagnosis can be challenging in the presence of nonneoplastic lymphoproliferative disease or bone marrow abnormalities. Awareness of susceptibility to malignant transformation and early diagnosis with multidisciplinary approach can save the patients' lives.

Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.

The effect of phototherapy on fecal calprotectin levels.

OBJECTIVE: Fetal calprotectin levels increase in the early stages of necrotizing enterocolitis. Although the effects of several factors on fetal calprotectin have been studied, the effect of phototherapy is not known. In this study, we analyzed the effect of phototherapy on fetal calprotectin levels. METHODS: Ninety breast-fed newborns (46 male, 44 female) who were hospitalized for indirect hyperbilirubinemia and treated with phototherapy were included to the study. Forty-two of them were term and 44 of them were preterm. Newborns treated with phototherapy (n = 53) constituted the phototherapy group (29 preterm, 24 term) and 37 newborns who did not receive phototherapy (19 preterm, 18 term) constituted the control group. Fecal samples were collected 24 hours after phototherapy had been started. Fecal samples (100 mg) were weighed with sensitive scales and preserved at -80°C after buffering with a special solution. All samples were studied at the same time with a fecal calprotectin kit by using enzyme-linked immunosorbent assay. RESULTS: There were no statistically significant difference between fecal calprotectin levels of term and preterm babies who received phototherapy and babies who did not receive phototherapy. CONCLUSION: There was no effect of 24-hour phototherapy on fecal calprotectin levels in preterm and term newborns.

A pediatric renal lymphoma case presenting with central nervous system findings.

UNLABELLED: In pediatric patients renal lymphoma frequently presents in the form of multiple, bilateral mass lesions, infrequently as a single or retroperitoneal mass, and rarely as diffuse infiltrative lesions. In patients with apparent central nervous system involvement close attention to other physical and laboratory findings are essential for preventing a delay in the final diagnosis. Herein we present a pediatric patient with renal lymphoma that presented with central nervous system findings that caused a delay in diagnosis. CONFLICT OF INTEREST: None declared.

The results of the modified St Jude Total Therapy XV Protocol in the treatment of low- and middle-income children with acute lymphoblastic leukemia.

The St Jude Total Therapy Study XV was the first clinical trial to prospectively use minimal residual disease levels during and after remission induction therapy to guide risk-directed treatment. We used the Total Therapy XV protocol with minimal modification in treating 115 newly diagnosed pediatric acute lymphoblastic leukemia patients from low- and middle-income groups from January 2011 to December 2017. The mean age at diagnosis was 5.97 ± 3.96 years. The median follow-up period was 88 months. Three (2.6%) patients had bone marrow relapse, and one (0.87%) had an isolated central nervous system relapse. Nineteen of the patients (16.52%) died due to infection-related complications, three (2.61%) died due to progressive disease, and one (0.87%) died due to hematopoietic stem cell transplant complications. Five-year overall survival was 80%, and event-free survival was 78.3%. Our results showed that the Total XV treatment protocol could be used successfully in patients with ALL from low- and middle-income populations. However, infection-related deaths remain a significant problem.

The utility of risk assessment tools for acute pulmonary embolism in children.

BACKGROUND AND AIM: Pulmonary embolism (PE) is a potentially life-threatening disease in children. The objective of the study is to evaluate the utility of adult-based pulmonary embolism rule-out criteria (PERC), Pediatric PE Model, and D-dimer in the diagnosis of PE in children. MATERIAL AND METHODS: The study consisted of patients under 18 years of age who were consulted to the Pediatric Pulmonology Clinic for the evaluation of PE. Patients were divided into two groups based on the confirmation of PE. The group with the presence of PE (n = 20) consisted of children who were diagnosed with PE. The group with the absence of PE (n = 28) consisted of children with clinically suspected PE but negative diagnostic imaging. Adult validated clinical decision PERC rule and Pediatric PE Model were retrospectively applied to the patients. RESULTS: In the study, PERC demonstrated a sensitivity of 60% and a specificity of 46% for the diagnosis of PE in children. When PE Model was evaluated for the children, it was found a 50% sensitivity and 75% specificity. Combining PE Model and PERC rule with D-dimer did not increase the specificity and sensitivity. Smoking was found to be relevant for PE in the childhood. Twenty-five percent of the patients had a genetic tendency for PE. All of the patients had an underlying disease as well. CONCLUSION: None of the current risk assessment tools (PE Model, PERC, D-dimer) were found to be accurate in predicting PE. Further larger population studies are still required to develop a better diagnostic approach.

Seeing Radiology Curricula Through Turkish Medical Students' Eyes: A Survey of Turkish Medical Schools' Radiology Education.

INTRODUCTION: Radiology education is essential for nonradiologist specialists and practitioners as well as for radiologists. We conducted a survey to gather the opinions of Turkish medical students from first to sixth grade regarding their radiology curricula, radiology education content, and perceptions of various imaging modalities and to assess the amount, adequacy, and homogeneity of radiology education in various schools. METHODS: Turkish medical students were reached by student ambassadors from 10 different schools of medicine via social media and email. They were provided with a 20-question survey-via the SurveyMonkey platform-related to their radiology curriculum and their perceptions of the radiology education at their schools and of different imaging modalities. Subjective parameters were scaled by a 4-point Likert scale and the results are reported by percentages of students. RESULTS: A total of 988 medical students (F/M: 61%/39%) from 41 different medical schools participated in this survey. Of those, 57% were preclinical students (≤ third year of medical school), while 43% were clinical students (> third year). More than half of the students (51%) stated that the amount of radiology education included in their curriculum was too little, while 44% of them stated it was just right and only 5% stated it was too much. Only 31% of the participants stated that they were able to review radiology images on their own. When asked about their level of confidence in identifying the position of lines and tubes, pneumonia, pneumothorax, and pleural effusion on chest radiographs, 41%, 39%, 41%, and 41% of the participants, respectively, stated that they were not confident. Thirty-five percent of the participants had not received any training in comparing normal to abnormal imaging of bone fractures, pneumonia, pleural effusion, subdural hemorrhage, or pneumothorax. The majority of the Turkish medical students in this survey had never heard (57%) nor used (64%) the American College of Radiology Appropriateness Criteria. CONCLUSIONS: The radiology curriculum in Turkey differs among various schools and most students stated that preclinical radiology course content was inadequate. Further studies and improvements must be conducted to provide high-quality, equitable radiology education that begins during preclinical training with respect to the students' opinions.

Venous thrombosis in a pseudohypoparathyroidism patient with a novel GNAS frameshift mutation and complete resolution of vascular calcifications with acetazolamide treatment.

Introduction Pseudohypoparathyroidism type IA (PHP1A) is characterized by end-organ resistance to multiple hormones and Albright's hereditary osteodystrophy (AHO). PHP1A is caused by inactivating mutations of the GNAS gene encoding the α-subunit of the stimulatory G protein (Gsα). In line with the underlying genetic defect, impaired inhibition of platelet aggregation has been demonstrated in some patients. However, no PHP1A case with thrombotic events has been described. Also, PHP1A cases typically have subcutaneous ossifications, but soft tissue calcifications are another common finding. Treatment options for those and other non-hormonal features of PHP1A are limited. Case Presentation A female patient presented with short stature, fatigue, and exercise-induced carpopedal spasms at age 117/12 years. Diagnosis of PHP1A was made based on hypocalcemia, hyperphosphatemia, elevated serum PTH, and AHO features, including short stature and brachydactyly. A novel frameshift variant was detected in the last exon of GNAS (c.1065_1068delGCGT, p.R356Tfs*47), showing complete loss of baseline and receptor-stimulated activity in transfected cells. The patient developed venous thrombosis and vascular and subcutaneous calcifications on both forearms after venous puncture on the right and extravasation of calcium gluconate during treatment on the left. The thrombosis and calcifications completely resolved following treatment with low molecular weight heparin and acetazolamide for 5 and 8 months, respectively. Conclusions This case represents the first PHP1A patient displaying thrombosis and the first successful use of acetazolamide for PHP1A-associated soft tissue calcifications, thus providing new insights into the treatment of non-endocrinological features in this disease.

Diabetic ketoasidosis is associated with prothrombotic tendency in children.

Children and adolescents with type I diabetes mellitus (DM) may present with diabetic ketoacidosis (DKA), which is associated with significant morbidity and mortality. This study aimed to evaluate the hematological parameters at diagnosis (0th hour) and 96th hour after the initiation of treatment in children with DKA. Twenty-six children with DKA treated in Dicle University Faculty of Medicine between September 2002 and August 2003 were included in this study. General characteristics of the patients and hematological parameters (platelet count, white blood cell count, prothrombin time, partial thromboplastin time (PTT), bleeding time, coagulation time, protein C, protein S, antithrombin III, fibrinogen, D-dimer, factor VIII, factor IX, and factor X levels) at diagnosis (0th hour) and 96th hour after the initiation of treatment were determined. The mean age of the children (10 girls and 16 boys) was 9.15 ± 3.85 years (range: 4-15 years). DKA developed for the first time in 58.3% of these children and they had recently been diagnosed as DM. After hematological parameters at 0th hour were evaluated, increased platelet count, decreased PTT, low protein C, and high factor VIII levels were determined at diagnosis, indicating prothrombotic tendency. If the hematological parameters at 0th hour were compared with those at 96th hour; platelet count decreased, PTT increased, protein C and factor VIII levels turned to be normal at 96th hour. When all the results are considered together, children with DKA appeared to have a prothrombotic tendency. Although this tendency was not reflected in clinical findings in this study, it should be kept in mind that children with DKA are prone to the development of thrombosis and they need to be investigated for the possibility of thrombosis.

Prognostic evidence of LEF1 isoforms in childhood acute lymphoblastic leukemia.

INTRODUCTION: The lymphoid enhancer factor 1 (LEF1) is a DNA-binding transcription factor that functions in the Wnt signaling pathway. Increased LEF1 activity is associated with progression of several types of cancer including leukemia. Here, we investigated LEF1 isoform expression and genomic variations in acute lymphoblastic leukemia (ALL). METHODS: LEF1 isoform expression was evaluated by quantitative real-time PCR in 87 newly diagnosed childhood ALL patients and controls. Moreover, Western blot analysis was performed for detection of LEF1 expression and the hotspot region of LEF1 was screened by deep sequencing. RESULTS: The LEF1 mRNA expression of B cell ALL patients was higher than the controls (LEF1-total P = .011, LEF1-long P = .026). Moreover, B-ALL samples showing higher total LEF1 expression had significantly shorter relapse-free survival (P = .008) and overall survival (P = .011). Although full-length LEF1 expression was similar to the controls in T-ALL, 50% (n = 15) of the ALL patients had increased full-length LEF1 protein expression. Imbalance between short- and full-length LEF1 isoforms may lead to cell survival in ALL. Beside the LEF1 activation, LEF1 gene variations were rarely observed in our cohort. CONCLUSION: The results indicate that the Wnt pathway may have a pathogenic function in a group of ALL patients and high LEF1-total expression might be a marker for shorter relapse-free survival time in B cell ALL.

Acute promyelocytic leukemia treated with idarubicin complicated by focal segmental glomerulosclerosis.

The authors report a 9-year-old boy presenting with a left cerebral ischemic infarction as the first manifestation of acute promyelocytic leukemia. During consolidation chemotherapy, the patient developed nephrotic syndrome and a renal biopsy revealed focal segmental glomerulosclerosis (FSGS). Remission in bone marrow was achieved with chemotherapy, however, new intracranial ischemic areas developed on follow-up. Acute promyelocytic leukemia complicated by FSGS has not been previously reported in children. There may be a relationship between anthracycline treatment and FSGS. Thrombosis could be related with both leukemia and nephrotic syndrome, here thrombosis was the initial symptom, before FSGS was diagnosed.

Treatment of pediatric Burkitt lymphoma in Turkey.

This study aimed to assess the demographic data and treatment results of children who were diagnosed with Burkitt lymphoma and treated according to the Berlin-Frankfurt-Münster-95 (BFM) protocol in a single institution. A total of 48 patients (37 boys, 77%) with a median age of 8 years (range 2 to 16 years) at diagnosis, were evaluated. Primary tumor sites were abdomen (70.8%), head and neck (22.9%), peripheral lymph node (2%), bone (2%), and testis (2%). The 5-year overall survival (OS) and event-free survival (EFS) were 78.1±4% and 76.6±6%, respectively. In univariate analysis, hemoglobin level less than 10 g/dL, cerebrospinal fluid (CSF) positivity and dialysis requirement at diagnosis were found to be important reverse predictor factors for EFS (P; 0.001, 0.001, 0.004, respectively). In multivariate analysis, hemoglobin level less than 10 g/dL and dialysis at diagnosis were found to be important reverse predictor factors for EFS (P; 0.0001). The EFS of our patients was lower than the values achieved with BFM-95 protocol in other centers. This study provides evidence that low hemoglobin level, CSF positivity and dialysis at diagnosis were important predictor factors for EFS in children with Burkitt lymphoma.

Preoperative sonography of nonreducible inguinal masses in girls.

PURPOSE: Inguinal hernia is one of the most common surgical pathologies in childhood. Any of the abdominal organs can slide into the hernial sac and become incarcerated there. In girls, the fallopian tubes, ovaries, uterus, and-rarely-ovarian cysts can form the sliding component of an inguinal hernia. The aim of this study was to investigate the diagnostic value of preoperative sonographic examination in girls with nonreducible inguinal masses. METHODS: Nine girls ranging in age from 2 months to 8 years who were admitted to our clinic with nonreducible inguinal masses were included in the study. All patients underwent sonographic examination followed by surgery on the day of admission. RESULTS: A definitive diagnosis was obtained in 6 patients on preoperative sonographic evaluation, whereas 3 patients were misdiagnosed. One patient was diagnosed sonographically as having lymphadenopathy, but surgery revealed an ovarian cyst sliding into the hernial sac. A second patient was found to have an infected lymph node at surgery instead of a strangulated bowel loop as diagnosed on sonographic examination. In the third patient, the preoperative sonographic diagnosis was an ovarian cyst in the hernia sac, but surgery revealed a cyst of the canal of Nuck. CONCLUSION: Inguinal masses in young girls must be carefully evaluated, because the sonographic preoperative diagnosis may be misleading.

The factors affecting persistent pneumothorax and mortality in neonatal pneumothorax.

The aim of this study was to present our experience in management of neonatal pneumothorax and factors contributing to persistent pneumothorax and mortality. Forty-two newborns were analyzed according to gestational age, birth weight, Apgar score, age of admittance, type of delivery, mother's age, side of pneumothorax, causes of pneumothorax, accompanying disorders, tube thoracostomy and mechanical ventilation durations, mean hospital stay, and deaths. Sixteen patients (38%) weighed less than 2500 g and 28 (66%) were preterm. The mean Apgar score at 5th minute was 6.2 (2-10). The pneumothorax was bilateral in 9 patients (21%). There was a defined underlying lung pathology in 26 (61%) patients and accompanying disorder in 14 (33%). Mean tube thoracostomy duration was 5 days (2-12). Twenty-five patients (59%) needed mechanical ventilation. Overall 10 babies died. Our findings indicated that underlying primary lung pathology, need for mechanical ventilation, and bilateral pneumothorax were major determinants of persistent pneumothorax and mortality in newborns.

Hematological and biochemical changes in volatile substance abusing street children in Istanbul.

The aim of the study is to assess the hematological and biochemical changes of inhalant abusing adolescences in Istanbul, Turkey. The study subjects comprised 24 street children. Demographic characteristics, hematological markers, complete blood count tests and white blood cell differential and liver function tests (alanine transaminase, aspartate transaminase, alkaline phosphatase) were evaluated. The blood cell counts and studied biochemical parameters were within normal range for age and sex matched adolescences. Anemia was observed in only one girl who had hypermenorea. The duration and the amount of substance abuse were investigated for a correlation with the blood parameters, only the amount showed the possibility of a trend associated with Hb and Hct (p<0.05). There was no significant relationship between the parameters except for the age. Although volatile abuse has been supposed to be related with anemia or other hematological abnormalities, we found no significant relation between volatile abuse and hematological or studied biochemical parameters. Alkaline phosphatase was the parameter found to be most affected, though being in normal range.

Relationship of Tel Hashomer criteria and Mediterranean fever gene mutations in a cohort of Turkish familial Mediterranean fever patients.

OBJECTIVE: To evaluate the frequency of 5 mutations and their relationship with the Tel Hashomer criteria in 85 FMF patients. METHODS: We looked for mutations in the Mediterranean fever (MEFV) gene in 84 consecutive patients who admitted to the Department of Medical Genetics of Afyon Kocatepe University, with a variable (from high to low) clinical suspicion of FMF. By using polymerase chain reaction and Hybridization-ELISA methods, 5 mutations (M694V, M694I, V726A, M680I and E148Q) have been studied between December 2002 and January 2005. RESULTS: We detected homozygote mutations in 12 patients (25.3%) and heterozygote mutations in 23 patients (48.9%) out of 47 patients with high clinical suspicion of FMF using Tel Hashomer criteria. In 12 patients (25.3%), no mutation was detected despite the clinical diagnosis of FMF was likely according to the Tel Hashomer clinical criteria. On the other hand, we detected homozygote mutations in 2 patients (5.4%) and heterozygote mutations in 17 patients (45.9%) out of 37 patients with low clinical suspicion of FMF using Tel Hashomer criteria. In 18 out of 37 patients (48.6%) in this group no mutation was detected. CONCLUSION: In patients with high or low clinical suspicion of diagnosis of FMF according to Tel Hashomer criteria, the frequency of homozygote patients was significantly higher than the frequency of patients with no mutation, but it was not higher than the frequency of heterozygote patients.