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.

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.

Bacterial agents causing meningitis during 2013-2014 in Turkey: A multi-center hospital-based prospective surveillance study.

This is an observational epidemiological study to describe causes of bacterial meningitis among persons between 1 month and 18 y of age who are hospitalized with suspected bacterial meningitis in 7 Turkish regions. covering 32% of the entire population of Turkey. We present here the results from 2013 and 2014. A clinical case with meningitis was defined according to followings: any sign of meningitis including fever, vomiting, headache, and meningeal irritation in children above one year of age and fever without any documented source, impaired consciousness, prostration and seizures in those < 1 y of age. Single tube multiplex PCR assay was performed for the simultaneous identification of bacterial agents. The specific gene targets were ctrA, bex, and ply for N. meningitidis, Hib, and S. pneumoniae, respectively. PCR positive samples were recorded as laboratory-confirmed acute bacterial meningitis. A total of 665 children were hospitalized for suspected acute meningitis. The annual incidences of acute laboratory-confirmed bacterial meningitis were 0.3 cases / 100,000 population in 2013 and 0.9 cases/100,000 in 2014. Of the 94 diagnosed cases of bacterial meningitis by PCR, 85 (90.4%) were meningococcal and 9 (9.6%) were pneumococcal. Hib was not detected in any of the patients. Among meningococcal meningitis, cases of serogroup Y, A, B and W-135 were 2.4% (n = 2), 3.5% (n = 3), 32.9% (n = 28), and 42.4% (n = 36). No serogroup C was detected among meningococcal cases. Successful vaccination policies for protection from bacterial meningitis are dependent on accurate determination of the etiology of bacterial meningitis. Additionally, the epidemiology of meningococcal disease is dynamic and close monitoring of serogroup distribution is comprehensively needed to assess the benefit of adding meningococcal vaccines to the routine immunization program.

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

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

Genetic associations of the response to inhaled corticosteroids in children during an asthma exacerbation.

BACKGROUND: Genetic associations of the response to inhaled corticosteroids (ICSs) during an asthma exacerbation are unknown. OBJECTIVE: To evaluate the role of genetic variants in the therapeutic response to high-dose ICS in children with moderate-to-severe asthma exacerbations. METHODS: Eighty-two children (56 boys/26 girls, mean age 9.6 ± 3.2 years) with moderate-severe asthma exacerbation were genotyped for eight single-nucleotide polymorphisms that were a priori associated with ICS response in chronic asthma treatment: glucocorticosteroid receptor (NR3C1) rs41423247; corticotrophin-releasing hormone receptor1 (CRHR1) rs242939, rs242941, and rs1876828; T-box 21 (TBX21) rs2240017; glucocorticoid-induced transcript 1 (GLCCl1); and T gene rs3099266 and rs2305089. Children were treated with a single high-dose (4000 µg) fluticasone propionate given by a nebulizer followed by 1000 µg/day of inhaled fluticasone propionate for 6 days. Primary outcome measure was the improvement in FEV1 at 4 h. RESULTS: Mean FEV1 was 71.7 ± 14.2% at presentation. Overall, fluticasone treatment resulted in a significant improvement in asthma score and FEV1 (p < 0.0001 for both). Children with the GG genotype at NR3C1 rs41423247 (n = 26) had a higher improvement in FEV1 [24.2% (interquartile range 11.5-36.3)] compared to those with CG+CC (n = 19), [7.9% (interquartile range 6.1-24.6) (p = 0.006)]. CONCLUSION: Homozygosity for the G allele at rs41423247 of the glucocorticosteroid receptor (NR3C1) gene is associated with a higher improvement in FEV1 at 4 h in children with moderate-to-severe asthma exacerbation treated with high-dose ICS. This observation may have important clinical implications especially for children who use systemic steroids frequently for recurrent asthma exacerbations.

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.

Clinical, radiological and laboratory findings in 185 children with tuberculous meningitis at a single centre and relationship with the stage of the disease.

BACKGROUND: A delay in the diagnosis and treatment of tuberculosis meningitis (TBM) may lead to increased mortality and morbidity. The aim of this study was to describe the clinical, radiological and laboratory findings of TBM on a cohort of 185 pediatric patients at a single centre over a 10 year period and to investigate relationship between the stage of the disease. METHODS: The hospital records of 185 TBM children that presented to the Pediatric Clinics of Dicle University Hospital were retrospectively evaluated. The age, gender, family history of tuberculosis, result of Mantoux skin test, status of BCG vaccination, stage of TBM at hospitalization, and clinical, laboratory and radiological features were recorded. Clinical staging of TBM was defined as follows: Stage I, no focal neurological findings and Glasgow Coma Scale (GCS) score 15; Stage II, GCS 15 presenting with focal neurological deficit or all the patients with GCS 10-14; Stage III, all the patients with GCS < 10. Relationships between results and stages of TBM were investigated. RESULTS: The mean age of the patients was 53.5 ± 44.9 months (4 months-18 years). 121 (65.4 %) of the patients were male and 64 (34.6 %) female. Family history of tuberculosis was defined in 62 (33.5 %) patients. Forty five (24.3 %) children had BCG vaccination scar. Mantoux skin test was interpreted as positive in 35 (18.9 %) patients. Sixty-eight (36.8 %) children were at stage I TBM, 57 (30.8 %) at stage II and 60 (32.4 %) were at stage III on admission. Mean duration of hospitalization was 23.9 ± 14.1 days. Totally, 90 patients (48.6 %) had abnormal chest X-ray findings (parenchymal infiltration in 46 (24.9 %), mediastinal lymphadenopathy in 36 (19.5 %), miliary opacities in 25 (13.5 %), pleural effusion in 2 (1.1 %), and atelectasis in 2 (1.1 %) patients). One hundred sixty seven (90.3 %) patients had hydrocephalus in cranial computerized tomography. There were 24 (13.0 %) patients with positive culture for Mycobacterium tuberculosis and 3 (1.6 %) patients with positive acid-fast bacilli in cerebrospinal fluid. Overall mortality rate was 24 (13.0 %). Among the findings; patients at Stage III had less frequent positive chest X-ray abnormality, miliary opacities and BCG vaccination scar when compared with patients at Stage I and II (p = 0,005; p = 0,007, p = 0.020, respectively). CONCLUSIONS: Children with TBM and positive chest X-ray findings at hospital admission were more frequently diagnosed at Stage I, and BCG vaccination might be protective from the Stage III of the disease.

A new experimental rat model of pancreatitis using Ecballium elaterium.

BACKGROUND: We originally aimed to determine the beneficial effects of Ecballium Elaterium (EE) on acute pancreatitis; however, we observed negative effects of EE on the pancreas. Thus, we used EE in rats to generate a new model of pancreatitis, which we compared with other established pancreatitis models. METHODS: A total of 32 Wistar albino rats were used. Rats were divided into 4 groups, each of which contained 8 rats. Group 1 (Control), Group 2 (L-Arginine (LA), Group 3 (LA + EE), Group 4 (EE): Twenty-four hours after that serum parameters were analyzed in the collected blood. Blood samples were transported on mice to the Biochemistry Laboratory following cardiac puncture. The levels of amylase, interleukin (IL)-6, interleukin (IL) 1-ß (IL-1ß), malondialdhyde (MDA), tumor necrosis factor (TNF)-α, total antioxidant status (TAS), and total oxidant status (TOS) were analyzed. Histopathological analysis: The pancreas and lung tissue samples obtained from the rats. Edema, inflammation, vacuolization, and necrosis of the pancreas were assessed using a scoring system ranging from 0 to 4. Edema, hemorrhage and inflammation of the lung tissue were evaluated using a scoring system ranging from 0 to 3. RESULTS: Histopathological analysis revealed that edema, inflammation, necrosis, and hemorrhage were significantly higher in the LA + EE group than in the control group. Moreover, necrosis was higher in the rats that received LA and EE compared to the rats that received only LA or EE. Increases in inflammatory mediator levels, including IL-6, IL-1ß, TNF-α, MDA, and TOS, were observed in all groups as compared to the control group. Moreover, lower TAS levels were detected in all groups but the control group. The increase in IL-1ß and TNF-α levels and the decrease in TAS were statistically significant in all groups (P < 0.05). CONCLUSIONS: EE may be used to create a successful acute pancreatitis (AP) model, resulting in edema, necrosis, hemorrhage, and inflammation of the pancreas. The major advantage of this model is that it does not require laparotomy, and can be implemented with only an intraperitoneal injection (IP). Moreover, EE may be combined with other agents, such as LA, to create severe pancreatitis. Further molecular studies are warranted to determine the underlying effects of EE on the pancreas.

Effects of Gluten-Free Diet on Quality of Life and Depression in Children With Celiac Disease.

OBJECTIVES: The aim of this study was to investigate the level of depression and quality of life in children with celiac disease (CD). In addition, it aimed to examine the relations of depression level and life quality with adherence to a gluten-free diet (GFD). METHODS: Twenty-five children with CD and 25 healthy controls were included. The Depression Scale for Children and the General Purpose Health-Related Quality of Life Scale for Children were performed on patients before and after receiving recommendations to follow a GFD. RESULTS: No significant differences were found in the depression scores between the patients and the control subjects (P > 0.05). In contrast, total scores and scores of the emotional well-being subscale of the measure of Quality of Life Scale for Children were significantly lower in patients with CD compared with the control group (P < 0.05). No significant improvements were observed in depression or life quality scores of the total subsample of celiac patients, all of whom received a recommendation to follow a GFD (P > 0.05). Significant decrease was observed in the depression scores, however, of celiac patients who were able to actually adhere to the GFD compared with nonadherent patients. CONCLUSIONS: CD negatively affected quality of life in children. Adherence to GFD was associated with reduction in depression symptoms. Improving the adherence of celiac patients to a GFD may have a favorable effect on their depression symptoms.

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.

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.

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.

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.

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.(AU)

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.(AU)

Tuberculosis congÞnita: presentación de un caso infrecuente / Congenital tuberculosis: presentation of a rare case

La tuberculosis congÞnita es una enfermedad rara, con alta tasa de mortalidad. Es considerada el resultado de la transmisión vertical de la infección desde la placenta al feto, a través de la aspiración de líquido amniótico o por vía transplacentaria a través de las venas umbilicales. El diagnóstico de la enfermedad suele ser difícil porque los signos clínicos son inespecíficos. Se presenta el caso de un lactante varón de 48 días de vida, que fue internado por pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria durante los últimos 20 días. Había recibido antibióticos de amplio espectro durante ese lapso, sin presentar mejoría. La radiografía de tórax mostró una consolidación con una lesión cavitaria en los campos medio y superior izquierdo. Se detectó Mycobacterium tuberculosis por reacción en cadena de la polimerasa en una muestra tomada por lavado broncoalveolar y, con ese hallazgo, se diagnosticó tuberculosis congÞnita. Se comenzó, entonces, el tratamiento con tuberculostáticos. El paciente falleció al 13er día de tratamiento. En lactantes con pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria, debiera considerarse la posibilidad de tuberculosis congénita.(AU)

Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress.(AU)

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.

Tuberculosis congènita: presentación de un caso infrecuente / Congenital tuberculosis: presentation of a rare case

La tuberculosis congènita es una enfermedad rara, con alta tasa de mortalidad. Es considerada el resultado de la transmisión vertical de la infección desde la placenta al feto, a través de la aspiración de líquido amniótico o por vía transplacentaria a través de las venas umbilicales. El diagnóstico de la enfermedad suele ser difícil porque los signos clínicos son inespecíficos. Se presenta el caso de un lactante varón de 48 días de vida, que fue internado por pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria durante los últimos 20 días. Había recibido antibióticos de amplio espectro durante ese lapso, sin presentar mejoría. La radiografía de tórax mostró una consolidación con una lesión cavitaria en los campos medio y superior izquierdo. Se detectó Mycobacterium tuberculosis por reacción en cadena de la polimerasa en una muestra tomada por lavado broncoalveolar y, con ese hallazgo, se diagnosticó tuberculosis congènita. Se comenzó, entonces, el tratamiento con tuberculostáticos. El paciente falleció al 13er día de tratamiento. En lactantes con pérdida de peso, fiebre, tos, hemoptisis y dificultad respiratoria, debiera considerarse la posibilidad de tuberculosis congénita.

Congenital tuberculosis is a rare disease with a high mortality rate. Congenital tuberculosis is considered the result of mother-to-child transmission from the placenta to the fetus, through the ingestion of the amniotic fluid, or via transplacental transmission through the umbilical vein. Given the non-specific clinical signs of tuberculosis, it is usually difficult to diagnose it. The case of a 48-day-old male infant hospitalized due to weight loss, fever, cough, hemoptysis, and respiratory distress for the past 20 days, is presented. In this period, he had received broad spectrum antibiotics but with no improvement. A chest x-ray showed the presence of consolidation and a cavitary lesion in the upper and middle left lung fields. Mycobacterium tuberculosis was detected by polymerase chain reaction in a bronchoalveolar lavage specimen. Congenital tuberculosis was diagnosed based on this finding; hence, a tuberculostatic regimen was started accordingly. The patient died 13 days after treatment initiation. Congenital tuberculosis should be considered in infants with weight loss, fever, cough, hemoptysis and respiratory distress.

Rhizomelic Chondrodysplasia Punctata Type 1 Caused by a Novel Mutation in the PEX7 Gene.

Peroxisomes are involved in various metabolic reactions. Rhizomelic chondrodysplasia punctata (RCDP) type 1 is one of the peroxisomal biogenesis disorders caused by mutations in the PEX7 gene and is inherited in an autosomal recessive manner. We present a nine-year-old boy with skeletal abnormalities and dysmorphic facial appearance. The patient was born to parents who were first cousins. Very-long-chain fatty acids and pristanic acid levels were in the normal range, but an elevated phytanic acid level was detected by gas chromatography/mass spectrometry. The PEX7 gene was sequenced in the patient and his parents. A novel homozygous mutation, c.192delT (p.F64Lfs*10), was identified in the patient and was present in heterozygosity in both parents. In conclusion, the clinical presentation and peroxisome profile of the patient suggest that this novel mutation leads to RCDP type 1.

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.