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Objective:To analyze the correlation between clinical phenotypes and genotypes in 6 children with primary distal renal tubular acidosis (dRTA).Methods:The clinical data of 6 children confirmed as dRTA in Wuhan Children′s Hospital, Tongji Medical College, Huazhong University of Science & Technology from November 2017 to August 2019 were collected, and related auxiliary examination was performed to assess their growth and development.The venous whole blood was reserved for Trio whole exome sequencing, and full spectrum genetic disease accurate diagnosis cloud platform was applied to systematic data screening and analysis.The suspected mutations were checked by Sanger sequencing, and then the role of protein was predicted by software.Results:Clinical manifestations, signs and auxiliary examination results of the 6 children accorded with the diagnostic criteria of dRTA, and the prominent characteristics was growth retardation.One case had knee valgus, one had osteoporosis, and the auxiliary examination results showed that both of them had alkaline urine, metabolic acidosis, and hypokalemia.Three children had nephrocalcinosis, and 2 children had nephrolithiasis.The parents of the 6 patients were all normal without phenotypes.Mutations in the SLC4A1 gene were identified in 4 patients, including 1 child with a reported homozygous autosomal recessive missense mutation(c.2102G>A, p.G701D), who had dRTA and hemolytic anemia, and 3 children with the reported de novo heterozygous autosomal dominant missense mutation(c.1766G>A, p.R589H, c.1765C>T, p.R589C), whose age at diagnosis was related to abnormal renal imaging.Compound heterozygous autosomal recessive mutations in the ATPV1B1 gene were identified in 1 patient, and they were novel heterozygous missense mutations (1153C>A, p.P385T and c. 806C>T, p.P269L). A novel homozygous autosomal recessive missense mutation was identified in 1 patient in the ATPV0A4 gene(c.1899C>A, p.Y633X, 208). Conclusions:Mutations in SLC4A1, ATP6V1B1, ATP6V0A4 genes are identified as the main causes of the primary dRTA, and the phenotypes was related to the mutation features and genotypes.Genetic test should be conducted on patients suspected as dRTA for early molecular diagnosis, thereby improving clinical phenotypic screening and individualized treatment.
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Objective To investigate the clinical manifestations and genetic features of children with papillorenal syndrome caused by PAX2 gene mutation.Methods Clinical manifestations,imaging changes and sequencing data were collected and analyzed from a family with papillorenal syndrome who were diagnosed in Wuhan Children's Hospital in February 2018."PAX2","papillorenal syndrome" and "renal coloboma syndrome" were used as key words to search in China National Knowledge Infrastructure,Wangfang Data Knowledge Service Platform,PubMed and Human Gene Mutation Database up to April 2018.Results A ten years old girl was admitted due to "edema and urine output decreased for one week".Lab showed BUN 25.30 mmol/L,Scr 766.5 μmol/L,Urine protein 3.6 g/24 h.Imaging examination showed bilateral vesical and ureter reflux combined with left duplex kidney and duplication of ureter.Developmental dysplasia of the left hip was also found.The father of the patient had been diagnosed with chronic kidney disease for 10 years and on hemodialysis for 6 years.Next generation sequencing revealed that both the father and daughter carried a heterozygous nonsense mutation in the exon3 c.219C ＞ G(p.Y73X) of PAX2.No Chinese literature ever was reported about papillorenal syndrome.Ninety-four articles in English were retrieved and 177 patients with papillorenal syndrome were confirmed by gene analysis with a total of 92 PAX2 variants.Ten nonsense mutations had been reported.Developmental dysplasia of the hip (DDH) never be reported before.Conclusion Papillorenal syndrome caused by PAX2 mutation can mainly manifest as abnormal development of both kidney and optic nerve,which may be accompanied by other systemic abnormalities,it is rarely reported in China.DDH may be a new phenotype of papillorenal syndrome.
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Objective To investigate the value of urinary calprotectin in differential diagnosis between prerenal and intrinsic pediatric acute renal injury(AKI).Methods A total of 68 cases with AKI were enrolled in this study,and they were divided into prerenal AKI group(25 cases) and intrinsic AKI group(43 cases) according to their tissue perfusion.The general data was collected,and the blood urea nitrogen(BUN),serum creatinie(Scr),BUN/Scr,potassium,fractional excretion of filtrated sodium(FENa),urine osmotic pressure,B-type natriuretic peptide (BNP),urinary calprotectin,neutrophil gelatinase-associated lipocalin (NGAL),kidney injury molecule 1 (Kim-1) were recorded and compared between the 2 groups.Results There were significant differences between prerenal AKI group and intrinsic AKI group in Scr[(439.0 ± 278.0) μmol/L vs.(603.0 ± 286.0) μmol/L,t =2.30,P ＜ 0.05],BUN/Scr (20.58 ±5.62 vs.14.93 ±4.32,t =4.65,P＜0.05),FENa[(1.5 ±0.6)％ vs.(8.1 ±2.6)％,t =12.46,P＜ 0.05],BNP[95.6(54.0,109.4) ng/L vs.512.3(320.1,520.3) ng/L,Z =2.21,P ＜0.05],urinary calprotectin [20.7(4.3,42.4) μg/L vs.402.4(60.1,498.7) μg/L,Z=3.13,P＜0.05] and NGAL[74.9(14.5,365.5) μg/L vs.684.2(56.2,1 502.5) μg/L,Z =2.35,P ＜0.05].Receiver operating characteristic curve analysis showed that urinary calprotectin[area under the curve(AUC) =0.940] and BNP(AUC =0.909) both had higher value in differential diagnosis.When the cut off value of calprotectin was 240.6 μg/L,its specificity was 96.0％ and the sensitivity was 86.0％.When the cut off value of BNP was 120.6 ng/L,its specificity was 92.0％ and the sensitivity was 90.7％.The diagnostic accuracy was low in Scr,but moderate in BUN,Scr,FENa and NGAL.BUN,potassium,urine osmotic pressure and Kim-1 had no diagnostic value.Conclusions Urinary calprotectin may have higher diagnostic value in the differential diagnosis between prerenal and intrinsic pediatric AKT.It can be used in the clinical diagnosis as a reference index.
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Objective To investigate the clinical efficacy of combined use of calcineurin inhibitor in the treatment of lupus nephritis in induction or maintenance,which is resistant to mycophenolate mofetil.Methods Sixty-six cases of children with lupus nephritis were selected from February 2014 to September 2016 in Huazhong University of Science and Technology,Tongji Medical College Affiliated Wuhan Children's Hospital.The randomized method was used to divide them into the control group and the observation group randomly.Among them,31 cases in the control group were given glucocorticoid,cyclophosphamide combined with traditional medicine for treatment;35 cases in observation group were given glucocorticoid,mycophenolate mofetil,tacrolimus (calcine phosphatase inhibitor) multi-target therapy for treatment.The clinical effect of 2 groups before and after treatment were compared,and the incidence of adverse reactions in the treatment of 2 groups of children were compared.Results After treatment,the levels of systemic lupus erythematosus disease activity index (SLEDAI),serum creatinine and 24 h urine protein [(6.05 ± 1.04) scores,(45.08 ± 18.52) μmol/L,(0.96 ±0.30) g/L] in the observation group were lower than those in the control group [(11.09 ±2.33) scores,(95.33 ±36.74) μmol/L,(2.05 ±0.74) g/L],and the differences were statistically significant (t =3.097,3.356,3.871,all P ＜ 0.05).Serum complement C3,plasma albumin levels [(1.05 ± 0.28) g/L,(63.24 ± 12.98) g/L] were higher than those in the control group [(0.34 ±0.10) g/L,(35.45 ±6.74) g/L],and the differences were statistically significant (t =4.124,3.567,all P ＜ 0.05).After treatment,the levels of serum complement C3 and plasma albumin were significantly higher between 2 groups than those before treatment,the differences were statistically significant (all P ＜ 0.05).The incidence of adverse reaction (14.29％,5/35 cases) in the observation group was lower than that in the control group (38.71％,12/31 cases),and the difference was statistically significant (x2 =5.128,P ＜ 0.05).Conclusion Multi-target combination therapy and traditional cyclophosphamide therapy can effectively control lupus nephritis in children,but the clinical effect of multi-target combination therapy is better and the adverse reaction is less.
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Objective To study the efficacy of sequential blood purification treatment of bee poisoning complicated by multiple organ disfunction syndrome (MODS).Methods The 11 cases of children with bee poisoning and MODS from Wuhan Children's Hospital were treated with sequential blood purification therapy,and they were treated with plasma exchange (PE),hemoperfusion (HP) and sequential continuous renal replacement therapy (CRRT) simultaneously in the early stage,and then were treated with intermittent hemodialysis (IHD) in the remission stage.Different modes of purification treatment were applied in different stages.The trends of liver function,renal function and myocardial enzymes were observed in 11 cases before and after therapy,later a retrospective analysis was performed,and the efficacy of sequential blood purification was studied.Results Ten in 11 cases of children were treated with HP,CRRT and IHD therapy,and among them 6 cases were treated with PE on the first day of admission.One case,the youngest of children admitted to hospital less than 24 hours,died of sudden cardiac arrhythmia due to toxic myocarditis.In ten cases of the children after treatment,their myocardial enzymes returned to normal at first,and then jaundice and hepatic function improved,and renal function gradually improved after 10 days.Two weeks after discharge,through reviewing of the liver and kidney function,myocardial enzymes returned to normal indicators.In review of urine,5 cases were accompanied with microscopic hematuria,3 cases were accompanied with hematuria and proteinuria,and 2 cases were completely normal.The improved cure rate was 91％ (10/11 cases).Conclusions Sequential blood purification treatment is the main and effective means for severe bee poisoning complicated with MODS in children in the early stage.