Urinary kidney injury molecules in children with febrile seizures.

OBJECTIVE: Hypoxia occurs following convulsions, and hypoxia is one of the most common causes of acute renal damage. The aim of this study was to investigate urinary levels of kidney injury molecules, including neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with febrile seizures (FS) for the first time. METHODS: The study included 28 children with FS and 34 age and gender matched healthy children. Serum biochemistry and blood gases were measured in the serum samples. Estimated glomerular filtration rate (eGFR) was calculated. NGAL, NAG, L-FABP, and creatinine (Cr) were measured in the urine samples. The ratios of kidney injury markers to urinary Cr were used for comparisons. RESULTS: There were no significant differences in eGFR and serum chemistry values between the FS and the control group (p > 0.05). Hypoxia was detected in 67.9% of the FS patients. The FS group had significantly higher urinary kidney injury molecules to Cr ratios compared to the controls, including NGAL/Cr (17.9 ± 9.8; 6.7 ± 4.0, respectively; p < 0.001), NAG/Cr (0.55 ± 0.29; 0.21 ± 0.16, p < 0.001), and L-FABP/Cr (4.85 ± 2.93; 1.74 ± 1.16, p < 0.001). CONCLUSION: Increased urinary NGAL/Cr, NAG/Cr, and L-FABP/Cr values, in patients with FS compared to healthy controls, suggest a possible subclinical renal damage in these patients.

Serum galectin-3 levels in children with chronic hepatitis B infection and inactive hepatitis B carriers.

BACKGROUND: Chronic hepatitis B virus (HBV) infection is common worldwide. Follow-up of patients by the use of non-invasive techniques may be valuable in clinical practice. The aim of this study was to investigate serum galectin-3 (GAL-3) levels for monitoring disease status in children with chronic HBV infection. MATERIAL/METHODS: Thirty-two patients with chronic hepatitis B (CHB), 30 inactive HBV carrier patients, and 30 matched healthy controls were enrolled in the study. We performed basic laboratory tests: serum glucose, albumin, alanine aminotransferase (ALT), aspartate aminotransferase, gamma-glutamyl transferase (GGT), total bilirubin, prothrombin time, and activated partial thromboplastin time. In addition, serum GAL-3 levels were measured by ELISA technique. RESULTS: Significantly higher serum GAL-3 levels (16.5±3.6, 1.1±0.3, 0.7±0.5 ng/ml, respectively, p<0.001) and ALT levels (80.2±30.6, 26.8±12.6, 28.1±4.4 IU/L, respectively, p<0.001) were found in the CHB group compared with the inactive carriers and the control groups. There were no significant differences in ALT levels and GAL-3 levels or between inactive HBV carriers and the control groups (p>0.05, for each). Significantly higher GGT levels were found in the CHB group (51.3±27.5 IU/L) compared with the inactive HBV carriers (35.7±10.1 IU/L) and the control group (31.3±9.5 IU/L) (p<0.001, and p=0.004, respectively). A significant correlation was found between GAL-3 and ALT levels in the CHB group (r=0.82, p<0.001). CONCLUSIONS: Our results suggest that serum GAL-3 level may be a beneficial indicator of chronicity in hepatitis B infection in children.

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

BACKGROUND: The aim of this study was to investigate the urine levels of human kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), N-acetyl-ß-D-glucosaminidase (NAG), and liver-type fatty acid-binding protein (L-FABP) in children with iron-deficiency anemia (IDA). MATERIAL AND METHODS: Thirty-five children with IDA and 32 matched healthy controls were recruited. We assessed complete blood count, serum iron, iron-binding capacity, ferritin, serum levels of urea, creatinine (Cr), sodium (Na), potassium (K), calcium (Ca), and glucose levels. Estimated glomerular filtration rate (eGFR) was calculated. Urinary NAG, NGAL, KIM-1, and L-FABP were measured and divided by urine creatinine for comparisons. RESULTS: There were no significant differences in serum urea, Cr, or eGFR between the IDA group and the control group (p>0.05, for all). IDA patients had significantly higher urine NGAL/Cr, L-FABP/Cr, KIM-1/Cr, and NAG/Cr compared with the control group (p<0.05). There were significant negative correlations between hemoglobin, hematocrit, red blood cell count, and urine NGAL/Cr, NAG/Cr, L-FABP/Cr, KIM-1/Cr levels (p<0.05). CONCLUSIONS: Higher urinary kidney injury molecule levels in IDA patients suggest a possible subclinical renal injury in pediatric IDA patients whose renal functions and serum electrolytes were normal.

Management of intestinal bleeding with single-dose cyclophosphamide in Henoch-Schönlein purpura.

In these case series, we report on six children (3 girls, 3 boys) aged 5-13 years with Henoch-Schönlein purpura (HSP) who developed severe gastrointestinal (GI) bleeding resistant to both 2 mg/kg or pulse (10-30 mg/kg) i.v. methylprednisolone. All patients responded to single-dose (500 mg/m(2) ) i.v. cyclophosphamide (CPA) and none of them developed new GI bleeding after CPA treatment. No patients required surgical intervention. Single high-dose CPA may be beneficial in HSP with severe GI involvement, in which bleeding is non-responsive to high-dose steroids.

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

BACKGROUND: The aim of this study was to investigate novel urinary biomarkers including N-acetyl-ß-D-glucosaminidase (NAG), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and liver-type fatty acid binding protein (L-FABP) in children with ß-thalassemia major (ß-TM). MATERIALS AND METHODS: Totally, 52 patients (29 boys, 23 girls) with ß-TM and 29 healthy controls (3-17 years) were included. Various demographic characteristics and blood transfusions/year, disease duration, and chelation therapy were recorded. Serum urea, creatinine, electrolytes, and ferritin and urinary creatinine, protein, calcium, phosphorus, sodium, potassium, and uric acid in first morning urine samples were measured and estimated glomerular filtration rate (eGFR) was calculated. Routine serum and urinary biochemical variables, urinary NAG to Creatinine (U(NAG/Cr)), U(NGAL/Cr), U(KIM-1/Cr), and U(L-FABP/Cr) ratios were determined. RESULTS: Patients had similar mean serum urea, creatinine and eGFR levels compared with controls (p > 0.05 for all). The mean urinary protein to creatinine (U(Protein/Cr)) ratio was significantly higher in patients compared to the healthy subjects (0.13 ± 0.09 mg/mg and 0.07 ± 0.04 mg/mg, respectively; p < 0.001). Significantly increased U(NAG/Cr) (0.48 ± 0.58 vs. 0.23 ± 0.16, p = 0.026) and U(NGAL/Cr) (22.1 ± 18.5 vs. 11.5 ± 6.17, p = 0.01) ratios were found in ß-TM patients compared with healthy controls. However, no differences were found in serum and urinary electrolytes or U(KIM-1/Cr) and U(L-FABP/Cr) ratios between patients and controls (p > 0.05). Significant correlations were found between urinary biomarkers and urinary electrolytes (p < 0.05). CONCLUSIONS: Our results suggest that urinary NAG and NGAL may be considered to be reliable markers to monitor renal injury in ß-TM patients.

Usefulness of mean platelet volume and neutrophil-to-lymphocyte ratio for evaluation of children with Familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an autoinflammatory disease characterized by recurrent attacks of serositis, fever, and rash. Clinical and subclinical inflammatory processes may contribute to atherosclerosis in FMF patients, with mean platelet volume (MPV) as a potential indicator for atherosclerosis risk and neutrophil-to-lymphocyte ratio (NLR) as a marker for subclinical inflammation in these patients. In this study, we investigated whether MPV can be used as an indicator for atherosclerosis risk and if NLR is a marker for subclinical inflammation in FMF patients. MATERIAL AND METHODS: The study consisted of 75 FMF patients in attack, 157 attack-free patients, and 77 healthy controls. White blood cell count neutrophil-to-lymphocyte ratio, platelet count, MPV, PDW C-reactive protein levels, and erythrocyte sedimentation rate were recorded. RESULTS: There were no significant differences between attack, attack-free, and control groups in terms of mean MPV and PDW value. NLR value was higher in the attack group. NLR value was similar in attack-free and control groups. CONCLUSIONS: We found that MPV and PDW values are similar in FMF patients and healthy controls. NLR was higher in FMF patients in the attack period. Therefore, our results suggest that MPV and PDW values do not predict atherosclerosis risk in pediatric FMF patients, and NLR may be an indicator for attack period but not attack-free period.

The MEFV mutations and their clinical correlations in children with familial Mediterranean fever in southeast Turkey.

The aim of this study was to determine the Mediterranean fever (MEFV) gene mutations and their clinical correlations in children with familial Mediterranean fever (FMF) in southeast Turkey. Clinical and laboratory characteristics of 147 (65 males, 82 females) consecutive children with FMF having a positive MEFV gene mutation were prospectively investigated. Patients with negative MEFV gene mutations or atypical FMF presentations and those from other regions of the country were excluded. Clinical manifestations and disease severity scores were recorded. The six most frequent MEFV mutations including M694V, V726A, R726H, P369S, E148Q and P369S were investigated by a reverse hybridization test method. The median age of study group was 9.0 years, median age at diagnosis was 7.8 years, median age at disease onset was 5.0 years, and median follow-up duration was 4.0 years. A positive family history of FMF and parent-to-offspring transmission was found in 58.5 and 42.2 % of families, respectively. The frequencies of independent alleles, with decreasing order, were E148Q (30.7 %), M694V (26.0 %), R761H (13.5 %), V726A (13.0 %), P369S (10.5 %) and M680I (6.3 %) in FMF patients. The M694V subgroup had higher mean disease severity score and longer attack duration compared with E148Q and other mutations subgroups (p < 0.05). Two patients with amyloidosis had the M694V homozygote genotype. In conclusion contrast to other regions and many other ethnicities of the world, the most frequent MEFV gene mutation was E148Q in southeast Turkey. The M694V mutation frequency was lower, and disease severity was relatively mild in FMF children of this region.

Delivery room blood pressure percentiles of healthy, singleton, liveborn neonates.

BACKGROUND: Arterial blood pressure (BP) is one of the four vital signs that reflect cardiovascular status in neonates. The present study aimed to obtain BP percentiles among healthy, singleton, liveborn neonates between 34 and 43 weeks of gestation who were less than 1 h old. METHODS: BP measurements were taken after birth in supine-positioned neonates in the delivery room using an oscillometric device. A total of 982 well-nourished neonates who did not require resuscitation, were not fetally malnourished, were not admitted to the neonatal intensive care unit and were without obvious congenital abnormalities were included in the study. RESULTS: Sex- and type-of-delivery-specific 5th and 95th percentiles BP measurements were obtained for gestation. Mean BP values for systolic, diastolic and mean of term neonates were 63.98 ± 12.29 mmHg, 38.34 ± 11.06 mmHg and 49.32 ± 11.33 mmHg, and late preterm neonates were 61.80 ± 12.46 mmHg, 33.17 ± 9.97 mmHg and 46.52 ± 10.8 mmHg, respectively. There were weak but significant correlations between birthweight, birth length and head circumference and systolic, diastolic and mean arterial BP values (r = 0.20, r = 0.15 and r = 0.20, respectively, P < 0.001). Neonates who were delivered vaginally had higher mean BP values for systolic, diastolic and mean than neonates delivered by cesarean section (P < 0.05). Female neonates had higher systolic BP values than male neonates (P < 0.05). CONCLUSION: Data presented in this study include sex- and delivery-mode-specific BP percentile curves using an oscillometric method and serve as a valuable reference for physicians in dealing with the management of singleton, liveborn late preterm and term newborns in the delivery room intensive care.

Are serum Netrin-4 levels predictive of preeclampsia?

OBJECTIVE: To investigate the levels of anti-angiogenic factors, namely sFlt-1 and Netrin-4, in patients with preeclampsia (PE). MATERIAL AND METHODS: Cord-blood (UC) sFlt-1 and Netrin-4 concentrations were measured in 30 patients with severe PE, 30 patients with PE and 30 control infants and their mothers (MS). RESULTS: Maternal sFlt-1 levels were significantly higher in the severe PE and PE groups than in the control group. There were no statistical differences among the three groups in maternal and fetal Netrin-4 levels. But Netrin-4 levels were found to be the lowest in the control group and higher in the PE and severe PE groups. The correlation analysis revealed a positive correlation between maternal sFlt-1 levels and maternal Netrin-4 levels (p = 0.012, and r = 0.263), maternal sFlt-1 levels and fetal sFlt-1 levels (p = 0.012, and r = 0.263). CONCLUSIONS: There was a positive correlation found between maternal sFlt-1 levels and maternal Netrin-4 levels. We are of the opinion that elevation in levels of Netrin-4 might be secondary to placental hypoxia occurring in PE. The present study led to the consideration of anti-angiogenic biomarkers (sFlt-1 and Netrin-4) on automated platforms for clinical use as an aid in establishing the diagnosis and prognosis of PE.

Prolonged QT dispersion is associated with pediatric syncope.

Bilici M, Fidanci-Dedeoglu Z, Demir F, Akin A, Türe M, Balik H, Tan I, Ertugrul S. Prolonged QT dispersion is associated with pediatric syncope. Turk J Pediatr 2019; 61: 85-91. We aimed to find out whether QT dispersion can be used as a diagnostic marker in terms of syncope type, and recurrence risk. Fifty-two patients (28 male, 53.8%) admitted to the pediatric cardiology clinic with syncope were compared with 50 healthy controls (28 male, 56%; mean age: 13.8±2.3 years, range: 11-17 years) for QT dispersion (QTd) and other electrocardiographic findings. Gender, age, echocardiography, blood pressure while standing and sitting, electrolyte levels, liver and kidney function tests, and QTd and QTcd (calculated with corrected QT: QTc) in electrocardiography (ECG) of patients were all evaluated. Patients` ages varied between 7-17 years and the mean age at first syncope was 13.9±2.4 years. Mean follow-up duration of the patients was 10±5 months (range: 5-18 months). Mean number of syncope attacks was 2.8±2.2. QTd (72±46 ms vs. 34±14 ms) and QTcd (77±45 ms vs. 33±14 ms) values of the patients were significantly longer, compared to control group (p < 0.001). The age, gender, QTd, and QTcd values did not differ between the subtypes of syncope based on pathogenetic mechanism. Additionally, these parameters did not differ in terms of the number of syncope recurrence and tilt test. Patients` complaints reduced after cardiologic evaluation and advice regarding prevention of syncope. We think that in follow-up period, education and preventive precautions that can be taken in the daily life must be emphasized, and drug treatment can be started in unresponsive cases.

Cordycepin prevents postoperative formation of intra-abdominal adhesion in a rat model: An experimental study.

BACKGROUND: The aim of the present study was to investigate whether cordycepin prevented adhesion formation in a rat model. METHODS: Rats were randomly assigned to 3 groups of 10 rats. CONTROL GROUP: The absence of adhesion was confirmed via laparotomy. Adhesion group: The cecum was removed from the abdomen and scraped with a dry gauze bandage until petechial hemorrhagic foci developed. Cordycepin group: The same surgical procedure was performed as in the adhesion group, and 10 mg/kg cordycepin was administered intraperitoneally. After 15 days, the rats were sacrificed humanely via cardiac blood withdrawal under anesthesia. The rats were then analyzed morphologically and histopathologically, and hydroxyproline (OH-p) and malondialdehyde (MDA) levels were measured. RESULTS: Macroscopic analysis revealed significantly less adhesion in the cordycepin group than in the adhesion group (p<0.01). Furthermore, significant histopathological improvement was also evident in the cordycepin group compared to the adhesion group (p<0.05). The levels of OH-p and MDA in blood and tissue were higher in the adhesion group than in the control group, and lower in the cordycepin group than the adhesion group. Interestingly, MDA level was significantly lower (blood: p<0.05; tissue: p<0.01) in the cordycepin group than in the adhesion group, whereas only tissue OH-p was significantly lower in the cordycepin group compared with the adhesion group (p<0.05). One rat in both adhesion group and cordycepin group died postoperatively. CONCLUSION: Results indicated that cordycepin effectively reduced adhesion in a rat abrasion model. Thus, this agent may be valuable to prevent postoperative adhesion.

Echocardiographic diagnosis of double-chambered left ventricle.

Double-chambered left ventricle (DCLV) is a rare congenital abnormality in which the left ventricle is divided into two separate chambers by a septum or anomalous muscular structure. The chambers are observed mostly parallel to each other without stenosis, and less frequently in a superior-inferior arrangement. An asymptomatic girl is presented here who was diagnosed with DCLV on echocardiographic examination that was performed for the evaluation of cardiac murmur detected by a pediatrician. She has been followed up without treatment.

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

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

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

Determining the Independent Risk Factors and Mortality Rate of Nosocomial Infections in Pediatric Patients.

The objective of this study was to determine the rate, independent risk factors, and outcomes of healthcare-associated infections in pediatric patients. This study was performed between 2011 and 2014 in pediatric clinic and intensive care unit. 86 patients and 86 control subjects were included in the study. Of 86 patients with nosocomial infections (NIs), there were 100 NIs episodes and 90 culture growths. The median age was 32.0 months. The median duration of hospital stay of the patients was 30.0 days. The most frequent pathogens were Coagulase-negative Staphylococcus, Acinetobacter spp., Klebsiella spp., and Candida spp. Unconsciousness, prolonged hospitalization, transfusion, mechanical ventilation, use of central venous catheter, enteral feeding via a nasogastric tube, urinary catheter, and receiving carbapenems and glycopeptides were found to be significantly higher in NIs patients. Multivariate logistic regression analysis showed prolonged hospitalization, neutropenia, and use of central venous catheter and carbapenems as the independent risk factors for NIs. In the univariate analysis, unconsciousness, mechanical ventilation, enteral feeding, use of enteral feeding via a nasogastric tube, H2 receptor blockers, and port and urinary catheter were significantly associated with mortality. In the multiple logistic regression analysis, only mechanical ventilation was found as an independent predictor of mortality in patients with NIs.

Correlation of mean platelet volume, neutrophil-to-lymphocyte ratio, and disease activity in children with juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) is a chronic inflammatory arthritis characterized by periods of remission and relapse. Mean platelet volume (MPV) is an indicator of systemic inflammation. In the present study, we aimed to determine the association between mean platelet volume (MPV), neutrophil/lymphocyte ratio (NLR), platelet distribution width (PDW) and clinical measures of diseases activity in children with JIA. The study included 115 patients with JIA (64 with active disease and 51 with inactive disease) and 64 age-gender matched healthy control subjects. Routine laboratory methods were used to measure white blood cell count (WBC), platelet count (PLT), neutrophil count, lymphocyte count, hemoglobin (Hb), MPV, PDW, NLR, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) in all subjects of both the patient and control groups. Active disease was associated with significantly increased MPV (8.23 ± 1.16 fl) compared with inactive disease (7.00 ± 1. 08 fl) and control subjects (6.77 ± 1.08 fl) P<0.001, P<0.001, P=NS, respectively). NLR was significantly higher in patients with active (2.11 ± 1.19) and inactive (2.03 ± 1.51) disease relative to the control subjects (1.33 ± 0.66) (P<0.001, P=0.017, respectively). Mean PDW was significantly higher in patients with active disease (17.84 ± 1.06) compared with the control group (17.19 ± 0.93) (P=0.01). Our results suggest that MPV may be a useful marker of disease activity in patients with JIA. Regular treatment may decrease platelet activation in JIA patients. However, NLR was not a predictive marker of disease activity in patients with JIA.

Assessment of epicardial adipose tissue thickness and the mean platelet volume in children with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an inflammatory disease, which is suggested to be associated with increased risk of atherosclerosis. Epicardial adipose tissue (EAT) thickness and the mean platelet volume (MPV) are parameters used in prediction of atherosclerotic risk in various conditions. These parameters were evaluated in children with FMF and compared with healthy controls. METHODS: Forty-five patients with FMF and 54 age- and gender-matched healthy controls were assessed. Duration of symptoms, age at diagnosis, duration of delay in diagnosis, frequency and duration of FMF attacks, disease severity scores, response to colchicine therapy, MEditerraneanFeVer (MEFV) gene mutations, and MPV values were recorded. EAT thicknesses were measured by echocardiography. RESULTS: Epicardial adipose tissue thicknesses of the children with FMF were found to be significantly greater than that of controls (5.1 ± 1.4 vs. 4.5 ± 0.9 mm, p=0.036). FMF patients had significantly higher MPV values compared with the controls (7.8 ± 1.1 vs. 7.3 ± 1.4 fl, p=0.044). Age at diagnosis, duration of delay in diagnosis, and MPV values were found to be correlated with EAT thickness in the patient group (r=0.49, p=0.001 for the former parameters and r=0.32, p=0.04 for MPV). CONCLUSION: Epicardial adipose tissue thickness and MPV values seem to be increased in children with FMF. These findings may indicate an increased risk of atherosclerosis in FMF patients.

High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey.

OBJECTIVE: The aim of this study was to investigate the spectrum of Mediterranean fever (MEFV) gene mutations and genotype-phenotype correlation in children with familial Mediterranean fever (FMF) in southeast Turkey. METHODS: A total of 507 children (274 females) with FMF and MEFV gene mutation(s) were included. A 15-year retrospective evaluation was conducted; parameters analyzed were: age, sex, age at symptoms onset, age at FMF diagnosis, delay between symptoms onset and diagnosis, FMF attack symptoms, and response to colchicine. Disease severity scores were calculated and MEFV mutation analysis was performed via real-time PCR for the 6 most frequent mutations. Children with comorbid diseases or tested negative for MEFV gene mutations were excluded to provide homogeneity. RESULTS: A family history of FMF was found in 60.2% (n=305) of patients. The most common symptoms reported for FMF attacks were abdominal pain (98.0%), fever (93.9%) and arthralgia (47.3%); 75.0% of patients (n=380) were heterozygous, 14.2% were homozygous (n=72) and 10.8% were compound heterozygous (n=55).The following MEFV gene mutation alleles were identified: E148Q (40.1%), M694V (25.9%), V726A (15.8%), R761H (7.4%), M680I (6.8%), and P369S (4.1%). The M694V subgroup had the lowest mean age of disease onset and the highest mean disease severity score, whereas the E148Q group had later mean disease onset and the lowest mean disease severity score (p<0.05). CONCLUSION: The highest E148Q mutation frequency and milder disease in the course of FMF in our study population may be due to geographic and ethnic background dissimilarities of southeast Turkey.

Alta frecuencia de variación de la secuencia de la mutación E148Q en niños con fiebre mediterránea familiar en el sureste de Turquía / High frequency of E148Q sequence variation in children with familial Mediterranean fever in southeast Turkey

Objetivo: El objetivo de este estudio fue investigar el espectro de las mutaciones genéticas localizadas en el gen de la fiebre mediterránea (MEFV) y la correlación entre el genotipo y el fenotipo en niños con fiebre mediterránea familiar (FMF) en el sureste de Turquía. Métodos: En el estudio se incluyeron 507 niños (274 eran de sexo femenino) con FMF y mutaciones genéticas localizadas en el gen MEFV. Se realizó una evaluación retrospectiva de 15 años; y se analizaron los siguientes parámetros: edad, sexo, edad al inicio de los síntomas, edad al diagnóstico de la FMF, demora entre el inicio de los síntomas y el diagnóstico, síntomas de ataque de la FMF y respuesta a la colchicina. Se calcularon los índices de severidad de la enfermedad y se realizó el análisis de la mutación del genMEFV mediante PCR en tiempo real para las seis mutaciones más frecuentes. Con el fin de aportar homogeneidad, se excluyeron los niños con comorbilidades o con un resultado negativo en las pruebas de mutaciones del gen MEFV. Resultados: Se encontró que el 60,2% (n= 305) de los pacientes tenían antecedentes familiares. Los síntomas más frecuentes que manifestaron durante los ataques de FMF fueron dolor abdominal (98,0%), fiebre (93,9%) y artralgia (47,3%); el 75,0% de los pacientes (n= 380) eran heterocigotos; el 14,2% homocigotos (n= 72) y el 10,8% heterocigotos compuestos (n= 55). Se identificaron las siguientes mutaciones en los alelos del gen MEFV: E148Q (40,1%), M694V (25,9%), V726A (15,8%), R761H (7,4%), M680I (6,8%), y P369S (4,1%). En el subgrupo M694V se observó una edad media más joven de inicio de la enfermedad y un puntaje medio más alto de gravedad de la enfermedad, mientras que el grupo E148Q tuvo un inicio medio de enfermedad más tardío y un puntaje medio más bajo de severidad de la enfermedad (p <0,05). Conclusión: La frecuencia más alta de la mutación E148Q y la enfermedad más leve en la evolución de la FMF en la población de nuestro estudio quizás se deba a las diferencias étnicas del sureste de Turquía.

Objective: The aim of this study was to investigate the spectrum of Mediterranean fever (MEFV) gene mutations and genotype-phenotype correlation in children with familial Mediterranean fever (FMF) in southeast Turkey. Methods: A total of 507 children (274 females) with FMF and MEFV gene mutation(s) were included. A 15-year retrospective evaluation was conducted; parameters analyzed were: age, sex, age at symptoms onset, age at FMF diagnosis, delay between symptoms onset and diagnosis, FMF attack symptoms, and response to colchicine. Disease severity scores were calculated and MEFV mutation analysis was performed via real-time PCR for the 6 most frequent mutations. Children with comorbid diseases or tested negative for MEFV gene mutations were excluded to provide homogeneity. Results: A family history of FMF was found in 60.2% (n= 305) of patients. The most common symptoms reported for FMF attacks were abdominal pain (98.0%), fever (93.9%) and arthralgia (47.3%); 75.0% of patients (n= 380) were heterozygous, 14.2% were homozygous (n= 72) and 10.8% were compound heterozygous (n= 55).The following MEFV gene mutation alleles were identified: E148Q (40.1%), M694V (25.9%), V726A (15.8%), R761H (7.4%), M680I (6.8%), and P369S (4.1%). The M694V subgroup had the lowest mean age of disease onset and the highest mean disease severity score, whereas the E148Q group had later mean disease onset and the lowest mean disease severity score (p<0.05). Conclusion: The highest E148Q mutation frequency and milder disease in the course of FMF in our study population may be due to geographic and ethnic background dissimilarities of southeast Turkey.