Rapid Trio Exome Sequencing for Autosomal Recessive Renal Tubular Dysgenesis in Recurrent Oligohydramnios

Oligohydramnios is not a rare prenatal finding. However, recurrent oligohydramnios is uncommon, and genetic etiology should be taken into consideration. We present two families with recurrent fetal oligohydramnios that did not respond to amnioinfusion. Rapid trio-whole-exome sequencing (WES) revealed mutations in the AGT gene in both families within 1 week. The first family had a compound heterozygous mutation with c.856 + 1G > T and c.857-619_1269 + 243delinsTTGCCTTGC changes. The second family had homozygous c.857-619_1269 + 243delinsTTGCCTTGC mutations. AGT gene mutation may lead to autosomal recessive renal tubular dysgenesis, a rare and lethal disorder that can result in early neonatal death. Both the alleles identified are known alleles associated with pathogenicity. Our findings suggest that trio-WES analysis may help rapidly identify causative etiologies that can inform prompt counseling and decision-making prenatally

Acute kidney injury in patients with Kawasaki disease

BACKGROUND: Kawasaki disease was well known for coronary artery abnormalities with few reports of incidence of acute kidney injury (AKI). Our aim was to identify the rate of AKI in patients with Kawasaki disease and its associated factors. ;METHODS: All patients with Kawasaki disease admitted to a medical center from February 2004 to August 2014 were evaluated. Data collection included serum creatinine level, serial echocardiography reports, white blood cell count, C-reactive protein level, alanine transaminase level, urine white blood cell count, and renal ultrasound reports if available. AKI was defined when a patient's serum creatinine level was higher than 1.5 times upper limits of age-specific serum creatinine levels. ;RESULTS: This cohort study included 332 patients (191 boys and 141 girls; aged 0.12 to 11.3 y, median 1.39 y) and 93 patients (28%) of them had AKI. Multivariate logistic regression revealed that age and alanine transaminase level were significantly associated with AKI (odds ratio (OR): 0.521, 95% confidence interval (CI): 0.377-0.718, P < 0.001, and OR: 1.003, 95% CI: 1.000-1.005, P = 0.017, respectively). ;CONCLUSION: This study demonstrated that AKI exists in substantial proportion of patients with KD. Young age and high alanine transaminase level are the main associated factors for AKI in these patients

Transfusion-dependent thalassaemic patients with renal Fanconi syndrome due to deferasirox use

AimDeferasirox is a new oral iron chelating agent with several cases reporting renal adverse events in recent years. Our aim was to identify the incidence of deferasirox-related Fanconi syndrome (FS) and its risk factors. ;MethodsAll transfusion-dependent thalassaemic patients who received deferasirox at the outpatient department of the National Taiwan University Hospital (NTUH) from January 2006 to February 2014 were evaluated. ;ResultsThis cohort study included 57 patients, and mean age of deferasirox initiation was 18.27.7 years. After 6.91.8 years of follow-up, 5 in 57 (8.8%) thalassaemic patients had FS. Age of starting deferasirox negatively correlated with incidence of FS (correlation coefficient -0.892, P=0.008). Other factors were not significantly associated with FS. Serum creatinine level at the start of deferasirox compared to at the end of study or onset of FS did not show significant change (P=0.277). All the deferasirox-related FS manifested with proximal renal tubular acidosis and hypophosphataemia, which needed specific treatment or withdrawal of deferasirox use. ;ConclusionsWe recommend that children, especially of young age, who regularly use deferasirox should undergo routine urinalysis and blood testing for early detection of FS. ;Summary at a Glance Deferasirox, an oral iron chelating agent, has been reported to induce Fanconi syndrome. In this cohort study 5 out of 57 patients with thalassaemia, treated with deferasirox, developed a Fancni syndrome that manifested as a proximal renal tubular acidosis and hypophosphataemia. Children receiving deferasirox treatment for their thalassaemia should have regular screening for the early detection of Fanconi Syndrome