Severe Lymphatic Disorder and Multifocal Atrial Tachycardia Treated with Trametinib in a Patient with Noonan Syndrome and SOS1 Mutation.

Noonan syndrome (NS) is a multisystemic disorder caused by germline mutations in the Ras/MAPK cascade, causing a broad spectrum of phenotypical abnormalities, including abnormal facies, developmental delay, bleeding diathesis, congenital heart disease (mainly pulmonary stenosis and hypertrophic cardiomyopathy), lymphatic disorders, and uro-genital abnormalities. Multifocal atrial tachycardia has been associated with NS, where it may occur independently of hypertrophic cardiomyopathy. Trametinib, a highly selective MEK1/2 inhibitor currently approved for the treatment of cancer, has been shown to reverse left ventricular hypertrophy in two RIT1-mutated newborns with NS and severe hypertrophic cardiomyopathy. Severe lymphatic abnormalities may contribute to decreased pulmonary compliance in NS, and pulmonary lymphangiectasias should be included in the differential diagnosis of a newborn requiring prolonged oxygen administration. Herein we report the case of a pre-term newborn who was admitted to our unit for the occurrence of severe respiratory distress and subentrant MAT treated with trametinib.

PNPLA3 I148M Polymorphism Influences Renal Function in Children With Obesity and Prediabetes.

OBJECTIVE: Nonalcoholic fatty liver disease negatively impacts on renal function with the contribution of the I148 M variant in the patatin-like phospholipase-containing domain 3 (PNPLA3) gene. We hypothesized that children with prediabetes present with a lower estimated glomerular filtration rate (eGFR) than those with normal glucose tolerance (NGT) and that the 148M PNPLA3 allele could play a worsening role. We aimed evaluating the influence of the I148 M PNPLA3 polymorphism on the relationship between the eGFR and prediabetes in children with obesity. METHODS: One thousand thirty-six children underwent to complete assessment and were genotyped for the I148 M PNPLA3 polymorphism. RESULTS: Patients with prediabetes showed lower eGFR levels (171.03 ± 40.32 vs. 190.80 ± 41.71 mL/min/1.73 m2; P = .001) and higher prevalence of nonalcoholic fatty liver disease (80% vs. 59%; P = .003) than those with NGT. Children with prediabetes showed lower eGFR levels than those with NGT (150.97 ± 14.56 vs. 192.88 ± 40.09; P < .0001) among carriers of the PNPLA3 148M allele. This was not confirmed among patients homozygous for the PNPLA3 I148 allele. A general linear model for eGFR variance confirmed an inverse and significant association of the eGFR with prediabetes in patients carrying the 148M PNPLA3 allele but not in patients homozygous for the PNPLA3 I148 allele. CONCLUSIONS: Prediabetes negatively affects renal function in children with obesity. This effect is heightened in patients carrying the PNPLA3 148M allele.

Acute Kidney Injury and Renal Tubular Damage in Children With Type 1 Diabetes Mellitus Onset.

CONTEXT: Acute kidney injury (AKI) and renal tubular damage (RTD), especially if complicated by acute tubular necrosis (ATN), could increase the risk of later chronic kidney disease. No prospective studies on AKI and RTD in children with type1diabetes mellitus (T1DM) onset are available. OBJECTIVES: To evaluate the AKI and RTD prevalence and their rate and timing of recovery in children with T1DM onset. DESIGN: Prospective study. SETTINGS AND PATIENTS: 185 children were followed up after 14 days from T1DM onset. The patients who did not recover from AKI/RTD were followed-up 30 and 60 days later. MAIN OUTCOME MEASURES: AKI was defined according to the KDIGO criteria. RTD was defined by abnormal urinary beta-2-microglobulin and/or neutrophil gelatinase-associated lipocalin and/or tubular reabsorption of phosphate < 85% and/or fractional excretion of Na (FENa) > 2%. ATN was defined by RTD+AKI, prerenal (P)-AKI by AKI+FENa < 1%, and acute tubular damage (ATD) by RTD without AKI. RESULTS: Prevalence of diabetic ketoacidosis (DKA) and AKI were 51.4% and 43.8%, respectively. Prevalence of AKI in T1DM patients with and without DKA was 65.2% and 21.1%, respectively; 33.3% reached AKI stage 2, and 66.7% of patients reached AKI stage 1. RTD was evident in 136/185 (73.5%) patients (32.4% showed ATN; 11.4%, P-AKI; 29.7%, ATD). All patients with DKA or AKI presented with RTD. The physiological and biochemical parameters of AKI and RTD were normal again in all patients. The former within 14 days and the latter within 2months. CONCLUSIONS: Most patients with T1DM onset may develop AKI and/or RTD, especially if presenting with DKA. Over time the physiological and biochemical parameters of AKI/RTD normalize in all patients.

Congenital Solitary Kidney from Birth to Adulthood.

PURPOSE: To evaluate the course of prenatally diagnosed and early-enrolled congenital solitary functioning kidney patients followed until adulthood and to identify risk factors for kidney injury. MATERIALS AND METHODS: Among all congenital solitary functioning kidney patients followed (1993-2018), we recalled 56 patients with prenatal diagnosis and congenital solitary functioning kidney confirmation at 1-3 months of life reaching at least 18 years of age. Serum uric acid, heavy smoking (≥25 cigarettes/day) and overweight/obesity were clustered as modifiable risk factors. Kidney injury was defined by estimated glomerular filtration rate <90 ml/minute/1.73 m2 and/or 24-hour ambulatory blood pressure monitoring confirmed hypertension and/or proteinuria. Modifiable risk factors and congenital anomalies of the kidney and urinary tract (CAKUT) of congenital solitary functioning kidney were evaluated as risk factors for kidney injury. RESULTS: The mean followup period was 21.1 years (range 18-33 years). Mild kidney injury was found in 15 out of 56 patients (26.8%). The mean age at proteinuria, reduced estimated glomerular filtration rate and hypertension onset was 19.7 years (1.2 SDS), 20.7 years (2.7 SDS), and 22 years (5.6 SDS), respectively. Patients with CAKUT of congenital solitary functioning kidney and with both CAKUT of congenital solitary functioning kidney and modifiable risk factors presented survival free from kidney injury of 0% at 22.2 and 24.2 years of age, respectively. Patients with modifiable risk factors presented 42.4% of survival at 30 years. Patients without CAKUT of congenital solitary functioning kidney nor modifiable risk factors presented 100% of survival at 30 years of age (p=0.002). The presence of CAKUT of congenital solitary functioning kidney was the only significant risk factor (HR 4.9; 95% CI 1.8-14.2; p=0.003). CONCLUSIONS: The outcomes of congenital solitary functioning kidney in early adulthood appear better than previously reported. Prompt diagnosis of congenital solitary functioning kidney, healthy lifestyle promotion and monitoring of serum uric acid may improve the prognosis of congenital solitary functioning kidney patients.