Background
Atypical hemolytic uremic syndrome (aHUS) is a chronic disease characterized by thrombotic microangiopathy and a high risk of end-stage kidney disease. Dysregulation and/or excessive ...activation of the complement system results in thrombotic microangiopathy. Interest in extrarenal manifestations of aHUS is increasing. This study aimed to determine the clinical characteristics of patients with extrarenal manifestations of aHUS in childhood.
Methods
This study included 70 children with extrarenal manifestations of HUS from the national Turkish aHUS Registry. The demographics, clinical characteristics, genetic test results, all treatments, and renal/hematologic status of aHUS patients with extrarenal involvement were recorded.
Results
The most common extrarenal manifestation was neurological system involvement (
n
= 46 27.2%), followed by gastrointestinal (
n
= 20 11.8%), cardiovascular (
n
= 12 7%), and respiratory (
n
= 12 7%) involvement. The patients with neurological involvement had a higher mortality rate and a lower estimated glomerular filtration rate (eGFR) than the other patients at last follow-up. Eculizumab (with or without plasma exchange/plasma infusion) treatment increased the renal and hematologic recovery rates.
Conclusions
The most common and serious extrarenal manifestation of aHUS is neurological involvement and treatment outcome findings presented herein are important to all relevant clinicians.
In a trial involving infants with grade III, IV, or V vesicoureteral reflux and no previous UTI, continuous antibiotic prophylaxis for 2 years provided a small but significant benefit in preventing a ...first UTI.
We assessed the effect of blood pressure control on left ventricular mass index (LVMI) and left ventricular hypertrophy (LVH).
Ninety-six patients (64 males) ≥9 months post-kidney transplantation ...from the 4C-T (Cardiovascular Comorbidity in Children with Chronic Kidney Disease-Transplantation) study were analyzed longitudinally (mean follow-up, 2.6±1.3 years). Cumulative systolic blood pressure (SBP)/diastolic blood pressure exposure was calculated as a time-averaged area under the curve and categorized: ≤50th, 50th to ≤75th, 75th to ≤90th, and >90th percentile (pct). We performed adjusted linear and logistic mixed models for LVMI and LVH, respectively.
At baseline, LVMI was 49.7±12.7g/m
with 64% (n=61) kidney transplantation recipients displaying LVH. Compared with patients with cumulative SBP exposure >90th pct, patients with cumulative SBP of 50th to ≤75th showed a significant LVMI reduction of -5.24g/m
(
=0.007). A similar tendency was seen for cumulative SBP≤50th (β=-3.70 g/m
;
=0.067), but patients with cumulative SBP of 75th to ≤90th pct showed no reduction. A post hoc analysis in patients with cumulative SBP≤75th revealed that median SBP exposure was at 57.5th pct. For cumulative diastolic blood pressure, a significant LVMI reduction was seen in all 3 categories ≤90th pct compared with patients >90th pct. Patients with cumulative SBP of ≤50th or 50th to ≤75th pct showed 79% or 83% lower odds of developing LVH, respectively. Patients with cumulative diastolic blood pressure ≤50th showed a tendency of 82% lower odds for LVH (95% CI, 0.03-1.07).
Continuous exposure to blood pressure below the 60th pct led to regression of LVMI and LVH. Our data suggest stricter blood pressure control, which needs to be substantiated in a randomized controlled trial.
LRIG2 Mutations Cause Urofacial Syndrome Stuart, Helen M.; Roberts, Neil A.; Burgu, Berk ...
American journal of human genetics,
02/2013, Letnik:
92, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Urofacial syndrome (UFS) (or Ochoa syndrome) is an autosomal-recessive disease characterized by congenital urinary bladder dysfunction, associated with a significant risk of kidney failure, and an ...abnormal facial expression upon smiling, laughing, and crying. We report that a subset of UFS-affected individuals have biallelic mutations in LRIG2, encoding leucine-rich repeats and immunoglobulin-like domains 2, a protein implicated in neural cell signaling and tumorigenesis. Importantly, we have demonstrated that rare variants in LRIG2 might be relevant to nonsyndromic bladder disease. We have previously shown that UFS is also caused by mutations in HPSE2, encoding heparanase-2. LRIG2 and heparanase-2 were immunodetected in nerve fascicles growing between muscle bundles within the human fetal bladder, directly implicating both molecules in neural development in the lower urinary tract.
The aim of the study was to assess the clinical features and outcome parameters of children with vesicoureteral reflux (VUR) based on gender and VUR grade.
Patients with VUR who were seen during ...routine follow-up visits at Ankara University Children's Hospital between January 2014-January 2015 were included in this retrospective study. Patient demographics, clinical course, laboratory investigations, imaging were noted.
Two hundred and twenty patients were recruited. Mean age at the time of diagnosis was 3,17 ± 3,08 years. Boys were diagnosed at younger ages as compared to girls (2.00 ± 2,59 vs. 3,81 ± 3.15, p < 0.001). Urinary tract infection (UTI) was the most common presentation. The second presentation form was antenatal hydronephrosis (AHN) which was more common in males (25.6 %, p < 0.001). Twenty-two percent of the patients had grade 1-2, 51 % grade 3 and 27 % grade 4-5 reflux. Patients with grade 4-5 reflux had more abnormal ultrasound (US) and Tech 99m dimercaptosuccinic acid scintigraphy (DMSA) findings and surgery was performed more frequently in this group (p < 0.001). In males, grade 4-5 reflux (43.6 % vs. 18.3 %), abnormal US (77 % vs. 54 %) and DMSA (77 % vs. 59 %) findings were more frequent (p < 0.05). In girls higher rates of UTIs, lower urinary tract dysfunction (LUTD) and spontaneous reflux resolution were seen (p < 0.05).
Despite younger age at diagnosis, spontaneous resolution was found lower in boys and they had more frequent AHN, more severe reflux, and radiological abnormalities.
Mayer-Rokitansky-Küster-Hauser anomaly originates from agenesis of the Müllerian duct including agenesis of the uterus and the vagina because of abnormal development of the uterine ducts. This ...syndrome may be accompanied by the upper urinary tract anomalies such as unilateral renal agenesis, ectopia of 1 or both kidneys, renal hypoplasia, horseshoe kidney, and hydronephrosis. We report a 16-year-old girl, with unilateral renal agenesis, herniating ovary, and renal cell carcinoma in her solitary kidney, associated with Mayer-Rokitansky-Küster-Hauser syndrome-the first case in the literature to our knowledge.
Chronic non-bacterial osteomyelitis (CNO) is an autoinflammatory bone disease of unknown aetiology. The relationship between CNO and familial Mediterranean fever (FMF) is not clearly documented so ...far. This cross-sectional study aims to evaluate the clinical and laboratory characteristics of a cohort of CNO patients within the context of its relationship with FMF and MEFV gene mutations.
Demographic and clinical data were extracted from electronic medical records of patients with CNO. The MEFV gene analysis was performed for all patients.
A total number of 18 patients with CNO with a median follow-up of 36.50 (13.00-84.00) months were included in the study. Five patients (27.8%) were found to have at least one exon 10 mutations (four with M694V and one with M680I). Four of them (22.2%) had homozygous or compound heterozygous mutations of the MEFV gene. Two patients had a previous diagnosis of FMF and developed CNO while FMF was under control. Patients with MEFV mutations had an earlier onset of CNO, higher acute phase reactants, lower haemoglobin concentrations, and a higher number of bone lesions at disease onset with a persistent course of disease more frequently.
Our results demonstrated an increased frequency of MEFV gene mutations in CNO and a more severe disease phenotype of CNO in patients with MEFV gene mutations. Physicians practicing in regions where FMF is prevalent should be aware of this relationship and ask about the symptoms of FMF in detail in patients with CNO. Moreover, FMF should be included in CNO-associated conditions.
The aims of this study were to explore whether the demographic and clinical features of paediatric familial Mediterranean fever (FMF) patients with different colchicine response vary or not and to ...determine whether colchicine response can be predicted in FMF patients.
Files of patients who have been on colchicine therapy for at least 6 months were retrospectively evaluated. Patients were divided into two groups: group I included patients with no attacks after colchicine and group II comprised patients with ongoing attacks. Thereafter group II was further divided into two groups according to the reduction rate of attack frequency: group IIA (>50%) and group IIB (≤50%).
The study group comprised 221 FMF patients (116 females, 105 males). There were 131 patients in group I and 90 patients in group II (54 in group IIA and 36 in group IIB). Leg pain and M694V homozygosity were more frequent in group II (P < 0.05). Final colchicine doses, disease severity scores and number of patients with elevated acute phase reactant levels (attack-free period) were significantly higher and colchicine compliance was lower in group II when compared with group I (P < 0.05). Erysipelas-like erythema (ELE), leg pain and protracted arthritis/protracted febrile myalgia/vasculitis were more frequently detected in group IIB (P < 0.05).
Colchicine response is excellent in the majority of FMF patients, however, colchicine unresponsiveness cannot be predicted easily at onset. More rarely encountered clinical findings such as ELE, leg pain and protracted complaints and M694V homozygosity may be a clue for less colchicine response.
Our knowledge about the frequencies of mutations in the Turkish population is based on the studies on the affected patients and hospital-based control groups. We aimed to determine the frequencies of ...MEFV gene mutations in a population-based field study in Turkey.
Turkish citizens aged between 5 and 65 years were included in the study. Cities from seven regions of Turkey were studied. Blood samples were obtained from individuals who gave permission for laboratory experiments, and they were analysed for 10 MEFV gene mutations.
Among 500 participants, MEFV mutations were found in 74 (14.8%). Sixty four (12.8%), 7 (1.4%), and 3 (0.6%) participants were heterozygous, compound heterozygous, and homozygous, respectively. Among inhabitants with heterozygous mutations, the most common heterozygous mutations were E148Q/- and M694V/-. Sixteen participants were found to be heterozygous for M694V, 2 were compound heterozygous for M694V/E148Q, and one was homozygous for M694V/M694V mutation; in total, the frequency of M694V allele was 4% (n=20). Twenty-three (4.6%) individuals were heterozygous for common mutations (M694V, M680I, V726A). Total allelic frequency was 8.4%.
Our study, which describes the MEFV mutational spectrum and distribution in a healthy Turkish population, found a carrier rate that is much higher than expected.
PDF
