Analysis of A Pedigree with Hereditary Coagulation Factor Ⅻ Deficiency Caused by Compound Heterozygous Mutations / 中国实验血液学杂志

OBJECTIVE@#To analysis clinical phenotype and potential genetic cause of a family affected with hereditary coagulation factor Ⅻ deficiency.@*METHODS@#The prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), D-Dimer (D-D), coagulation factor Ⅻ activity (FⅫ:C) and coagulation factor Ⅻ antigen (FⅫ:Ag) were determined for phenotype diagnosis of the proband and his family members(3 generations and 5 people). Targeted capture and whole exome sequencing were performed in peripheral blood sample of the proband. Possible disease-causing mutations of F12 gene were obtained and further confirmed by Sanger sequencing. The corresponding mutation sites of the family members were analyzed afterwards. The online bioinformatics software AutoPVS1 and Mutation Taster was used to predict the effects of mutation sites on protein function.@*RESULTS@#The APTT of the proband was significantly prolonged, reaching 180.9s. FⅫ:C and FⅫ:Ag of the proband was significantly reduced to 0.8% and 4.17%, respectively. The results of whole exome sequencing displayed that there were compound heterozygous mutations in F12 gene of the proband, including the c.1261G＞T heterozygous nonsense mutation in exon 11 (causing p.Glu421*) and the c.251dupG heterozygous frameshift mutation in exon 4 (causing p.Trp85Metfs*53). Both mutations are loss of function mutations with very strong pathogenicity, leading to premature termination of the protein. AutoPVS1 and Mutation Taster software predicted both mutations as pathogenic mutations. The results of Sanger sequencing revealed that c.1261G＞T heterozygous mutation of the proband was inherited from his mother, for which his brother and his daughter were c.1261G＞T heterozygous carriers. Genotype-phenotype cosegregation was observed in this family.@*CONCLUSION@#The c.1261G＞T heterozygous nonsense mutation in exon 11 and the c.251dupG heterozygous frameshift mutation in exon 4 of the F12 gene probably account for coagulation factor Ⅻ deficiency in this family. This study reports two novel pathogenic F12 mutations for the first time worldwide.

Diagnosis of the accurate genotype of HKαα carriers in patients with thalassemia using multiplex ligation-dependent probe amplification combined with nested polymerase chain reaction / 中华医学杂志(英文版)

BACKGROUND@#Patients carrying the HongKongαα (HKαα) allele and -α/ααα could be misdiagnosed as -α/αα by the current conventional thalassemia detection methods, leading to inaccurate genetic counseling and an incorrect prenatal diagnosis. This study was aimed to accurately analyze the genotypes of HKαα carriers and -α/ααα.@*METHODS@#Samples were collected in our hospital from July 2017 to October 2019. Twenty-four common types of Chinese thalassemia were screened by gap-polymerase chain reaction (Gap-PCR) and reverse dot blot (RDB). Anti-4.2 multiplex-PCR was used to confirm carriers of the ααα duplication with -α deletion. Two-round nested PCR and multiplex ligation-dependent probe amplification (MLPA) were applied to accurately identify and confirm their genotypes. For data analysis, we used descriptive statistics and Fisher's exact tests.@*RESULTS@#Two thousand five hundred and forty-four cases were identified as thalassemia in 5488 peripheral blood samples. The results showed that α, β, and αβ compound thalassemia were identified in 1190 (46.78%), 1286 (50.55%), and 68 (2.67%) cases, respectively. A total of 227 samples from thalassemia patients were identified as -α/αα by Gap-PCR, and the genotypes of two samples were uncertain. There was a difference between Gap-PCR and combined groups (Gap-PCR combined with nested PCR and MLPA) in detecting HKαα (P < 0.05). Among the 229 patients, 20 patients were identified as HKαα carriers and one was identified as -α/ααα by two-round nested PCR and MLPA, including 15 patients with HKαα/αα, three with HKαα/αα and β-thalassemia coinheritance, one with HKαα/--, one with HKαα/-α and β-thalassemia coinheritance, and one with -α/ααα and β-thalassemia coinheritance.@*CONCLUSIONS@#ααα and HKαα genotypes of patients carrying -α need to be detected to reduce the misdiagnosis rate of patients carrying HKαα and -α3.7/ααα alleles. More accurate genetic counseling can be provided in the clinic using nested PCR combined with MLPA.

Retrospective clinical features and renal pathological analysis of 15 children with anti-neutrophil cytoplasmic antibody-associated vasculitis / 中华儿科杂志

<p><b>OBJECTIVE</b>Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis is a disorder with poor prognosis. This study aimed to improve the diagnosis and treatment of ANCA associated vasculitis of children, to analyze the clinical features, pathological characteristics and the prognosis of children with ANCA-associated vasculitis.</p><p><b>METHOD</b>Fifteen children with ANCA associated vasculitis who were hospitalized from 2003 to 2012 in our hospital were included. Their data of pre-diagnosis status, clinical manifestations, renal pathology, treatment and prognosis were reviewed retrospectively.</p><p><b>RESULT</b>Of the 15 children, 11 were girls and 4 boys with a mean age of 10.7 years. Fourteen children were categorized as microscopic polyangitis. The time to diagnosis varied from 0.5 month to 40 months. Hematuria and proteinuria were revealed by urine analysis in all of them, only 6 children complained with gross hematuria or edema of oliguria. Decreased glomerular filtration rate was revealed in 13 children, 8 of whom had a creatinine clearance rate of less than 15 ml/(min·1.73 m(2)). Twelve children underwent renal biopsy, crescent formation was found in 11 children. Most of the crescents were cellular fibrous crescents or fibrous crescents. Six children were diagnosed as crescentic nephritis; the process of rapidly progressive nephritis was only observed in 2 children. Segmental glomerulosclerosis or global glomerulosclerosis were found in 10 children, 3 of them were diagnosed as sclerotic glomerulonephritis. Anemia and pulmonary injury were the most common extra renal manifestations. Other extra renal manifestations included rash, pain joint, gastrointestinal symptoms, abnormal findings of cardiac ultrasonography and headache. Eight children were treated with steroid combined with cyclophosphamide, 4 were treated with steroid and mycophenolate mofetil, 2 were treated with steroid, cyclophosphamide and mycophenolate mofetil, 3 children were treated with plasma exchange. Fourteen children were followed up for 0.5 month to 4 years. The renal function did not recover in children with creatinine clearance rate of less than 30 ml/(min·1.73 m(2)), who showed crescentic glomerulonephritis or sclerotic glomerulonephritis. The children who had creatinine clearance rate of more than 30 ml/(min·1.73 m(2))had better prognosis.</p><p><b>CONCLUSION</b>More attention should be paid to ANCA-associated vasculitis among school age girls with anemia or pulmonary diseases. The renal damage was serious in children; however, the clinical manifestations were not obvious. Children with a creatinine clearance rate of less than 30 ml/(min·1.73 m(2)) had poor prognosis. Early accurate diagnosis is very important.</p>

Real-time quantitative detection of E2A-PBX1 fusion gene in children with acute lymphoblastic leukemia and its clinical application in minimal residual disease monitoring / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To establish a real-time reverse transcription-polymerase chain reaction (RT-PCR) for quantitative detection of E2A-PBX1 fusion gene mRNA in acute lymphoblastic leukemia (ALL) children and to explore its clinical significance in minimal residual disease monitoring and prognosis evaluation.</p><p><b>METHODS</b>Real-time RT-PCR was used to quantitatively detect the mRNA expression of E2A-PBX1 gene in 11 newly diagnosed ALL patients at diagnosis (11 cases), complete remission (11 cases) and periods of relapse (3 cases). Ten children with normal bone marrow cell morphology and without hematopathy or tumor diseases were used as the control group.</p><p><b>RESULTS</b>The median expression levels of E2A-PBX1 fusion gene in the ALL group at diagnosis and the relapse group were significantly higher than in the control and complete remission groups (P<0.01). Compared with E2A-PBX1 negative patients on day 33 during induction of remission, the recurrence rate increased and disease free survival rate at 3 year decreased significantly in E2A-PBX1 positive patients decreased (P<0.05).</p><p><b>CONCLUSIONS</b>Measurement of E2A-PBX1 levels by real-time RT-PCR is useful for monitoing minimal residual disease, prediction of relapse and individual treatment. The expression level of E2A-PBX1 gene on day 33 during induction of remission can be used for prognosis evaluation.</p>

Characteristics of repeated renal biopsy-proven primary focal segmental glomerulosclerosis in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To analyze the characteristics of repeated renal biopsy-proven primary focal segmental glomerulosclerosis (PFSGS) in 8 children, and to reveal the relationship between clinical features and pathology, between the two times of renal biopsy pathology, and the indications for repeated renal biopsy.</p><p><b>METHOD</b>The records of cases who ever experienced renal biopsy in this hospital were reviewed, of whom 8 cases of repeated renal biopsy-proven PFSGS were enrolled. The clinical manifestations, the reason why they had renal biopsy again, the difference in renal pathological findings, between the two biopsies and their therapeutic response. The classification of focal segmental glomerulosclerosis (FSGS) was based on the new criteria suggested by D'Agati in 2004.</p><p><b>RESULT</b>Of the 8 cases, age of onset ranged from 1 to 12 years, all were diagnosed as nephrotic syndrome (NS), the age of first biopsy ranged from 1.1 to 15.0 years, and the follow-up period was 10 months to 14 years. The reason for repeated biopsy was poor therapeutic response, continuous heavy proteinuria, or the progressive renal dysfunction. Four cases had the both biopsies in this hospital, and the first renal pathology showed minimal change disease (MCD), mesangial proliferation, FSGS CELL type and FSGS GTL type. After the second biopsy, they were additionally treated with immunosuppressive agents or switched to another one, 2 cases with FSGS COLL type presented renal dysfunction or end stage renal disease (ESRD), 1 case who developed the disease at 1.4 years of age, presented renal dysfunction at 10 months follow-up. The remaining 5 cases acquired complete remission.</p><p><b>CONCLUSION</b>FSGS is a clinicopathological syndrome, NS predominates clinically. It often indicates pathologic transformation when the patients show poor therapeutic response or continuous heavy proteinuria without remission. Mesangial proliferation can convert into FSGS, and the subtype of FSGS can shift. FSGS COLL type and onset at young age may suggest poor prognosis.</p>

Detection of WT1 gene in acute myeloid leukemia children by real-time fluorescent quantitative RT-PCR and its clinical significance / 中国实验血液学杂志

Objective of this study was to establish a SYBR Green Ireal-time reverse transcription-polymerase chain reaction (RT-PCR) for quantitative detection of WT1 gene mRNA in children with acute myeloid leukemia (AML) and investigate its clinical significance. SYBR Green Ireal-time RT-PCR was used to quantitatively detect the mRNA expression of WT1 gene in 30 newly diagnosed AML patients, 12 cases of remission (30), 18 relapsed patients and 30 cases of normal bone marrow cell morphology, and dynamically to detect the expression of WT1 gene in 20 newly diagnosed AML children. ABL served as internal reference gene, and the 2(-ΔΔct) method was used to calculate the relative expression. The results showed that (1) the expression of WT1 gene in newly diagnosed AML children was higher than that of the normal controls and the patients with remission (p < 0.001); there were no significant difference of WT1 gene expression between AML patients with remission and normal controls (p > 0.05), which were same as in relapsed patients and newly diagnosed patients (p > 0.05); (2) WT1 gene in 20 newly diagnosed AML children highly expressed before the children were initially treated, decreased when they were complete remission, then expression increased again when their AML relapsed. The WT1 gene expression level began to rise in 5 cases before clinical relapse at 5 - 7 months; (3) the complete remission rate (CR) and 3 year overall survival (OS) did not show significant difference between the WT1-positive group and negative group when dynamically monitoring WT1 gene expression of 20 newly diagnosed children with AML. 3-year OS of WT1-positive group at the 22 - 30 days after initial treatment was significantly lower than that of the negative group (p < 0.05). It is concluded that SYBR Green Ireal-time RT-PCR is a rapid, efficient, sensitive and specific method. WT1 gene in AML childhood plays a role of cancer-promoting. The change of WT1 gene expression level contributes to evaluate the therapeutic efficacy, detect the minimal residual diseases and analyze the prognosis.

Clinicopathological study of 212 children with primary focal segmental glomerular sclerosis / 中华儿科杂志

<p><b>OBJECTIVE</b>To evaluate the correlation between clinico-pathological features and outcome of children with primary focal segmental glomerular sclerosis (FSGS).</p><p><b>METHOD</b>A total of 212 pediatric patients with D'Agati (2004) primary FSGS were included in this study between 1997 and 2008. According to FSGS histologic classification criteria, 5 pathologic variants were recognized: collapsing (COLL), cellular (CELL), glomerular tip lesion (GTL), perihilar, and not otherwise specified (NOS). Retrospective analysis of the therapeutic response, the relationship between the clinical efficacy and pathology and the outcome of the patients was made.</p><p><b>RESULTS</b>Of the 212 patients, 178 (83.9%) had nephritic syndrome (NS), 97 (45.8%) had simple NS, 81 (38.2%) had nephritis-type NS, GTL variants were mostly appeared to be nephritic syndrome (n = 28) and COLL variants were the fewest (n = 11). The difference between the two variants had statistical significance (P < 0.05). Fourteen cases (6.6%) had nephrotic proteinuria, 20 cases (9.4%) had proteinuria with micro-hematuria. According to histologic classification, NOS (n = 86, 40.6%) was the most common type; perihilar type was seen in 25 cases (11.8%); CELL was seen in 58 cases (27.4%), COLL in 12 cases (5.6%), GTL in 31 cases (14.6%). Chronic tubular injury was present in most cases. CEL variants were mostly found in the early infancy. GTL and NOS variants initially appeared to be responsive to steroids, but subsequently became resistant or frequently recurrent; CELL and COLL appeared to be primarily steroid resistant, GTL and COLL variants had statistically significant differences (P < 0.05). The patients were followed-up for 5 months to 10 years. A response to therapy was observed in 50%, COLL FSGS had the highest rate of ESRD; 2 years renal survival rates were 67%, 3 years were 41%.</p><p><b>CONCLUSIONS</b>FSGS is defined as a clinicopathologic syndrome manifesting proteinuria and focal and segmental glomerular sclerosis with foot process effacement. The location of the sclerosis within the glomeruli proved to have prognostic significance. Collapsing glomerulopathy is the most aggressive variant of FSGS. Compared with other variants, GTL variant may be the best type. Different histologic variants of FSGS have substantial differences in clinical features at the time of biopsy diagnosis and substantial differences in renal outcomes. Prolonged treatment of FSGS-NS with corticosteroids and immune suppressive agents may have some effects in achieving sustained remission and improve prognosis in children.</p>

Clinical and pathological characteristics of children with dense deposit disease / 中华儿科杂志

<p><b>OBJECTIVE</b>To analysis the clinical and pathological characteristics of children with dense deposit disease (DDD).</p><p><b>METHODS</b>12 Children diagnosed as DDD by electron microscope were enrolled in this study. The clinical and pathological data were analyzed.</p><p><b>RESULTS</b>Of the 12 cases, 7 were males and 5 females, mean age 9.1 +/- 3.9 (5-13) years at onset, the duration from onset to renal biopsy was 1 month to 5 years and the follow-up period was 1-9 years. All cases had heavy proteinuria >50 mg/(kg x d), and persistent microscopic hematuria with recurrent gross hematuria during the course. Seven cases had hypertension (> or = 140/100 mm Hg, 1 mm Hg =0. 133 kPa), 5 cases had transient or recurrent abnormal renal function, and mild to severe anemia were observed in 8 cases respectively. All the cases had lower serum C3 (0.15-0.55 g/L). Clinically, 10 cases were diagnosed as nephritic syndrome (one case had partial lipodystrophy at the same time), and 2 cases were diagnosed as acute nephritic syndrome. Immunofluorescence study showed intense deposition of C3 along GBM, TBM and the wall of Bowman's capsule in a ribbon-like pattern and in the mesangial regions as coarse granules in all the cases. Under light microscopy, 9 cases showed the feature of membrane proliferative glomerulonephritis (MPGN), 1 case with focal segmental glomerulosclerosis (FSGS), 1 case with endocapillary proliferative glomerulonephritis (EnPGN) and 1 case with proliferative sclerosis (PSGN). Crescents were seen in 3 cases. Under electron microscopy, ribbon-like or linear electron-dense intramembranous deposits were identified in the lamina dense of GBM, and often along TBM and the wall of Bowman's capsule. All patients showed steroid resistance. After methylprednisone treatment, some patients showed transient remission. During the follow- up stage of 1-9 years, 3 cases showed normal urinalysis, 5 cases showed partial remission, 2 cases progressed to end stage renal disease (ESRD) and 2 cases were lost.</p><p><b>CONCLUSION</b>DDD is an in dependently rare disease with pathological-clinical varieties. Children with DDD presented with persistently lower C3, heavy proteinuria, recurrent gross hematuria and anemia. The characteristic immunopathologic finding is intense deposition of C3 along the GBM. Under electron microscopy, ribbon-like or linear electron-dense deposits in the lamina dense of the GBM, TBM and the wall of Bowman's capsule. Electron microscopic examination to demonstrate the intramembranous dense deposits is definitive diagnosis, regardless of the finding of light microscopy. All of them showed steroid resistant. Patients with steroid and CTX treatment showed some clinical improvement of their urinalysis.</p>

Mutation analysis of the PAX6 gene in a family with congenital aniridia and cataract / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation in the PAX6 gene in a family with congenital aniridia and cataract.</p><p><b>METHODS</b>Total genomic DNA was extracted from peripheral blood leukocytes of 12 family members including three living affected members and 96 unrelated healthy controls. The coding exons 4-13 of the PAX6 gene with intronic flanking sequences were amplified by polymerase chain reaction (PCR). By comparing sequences of the affected members with that of normal individuals, the disease-causing mutation was detected by direct DNA sequencing.</p><p><b>RESULTS</b>A PAX6 mutation was identified in the 3 patients, which did not exist in the unaffected members and unrelated healthy individuals. The nonsense mutation of C to T was detected at the nucleotide 1143, which converted the Arg codon (CGA) to a stop codon(TGA) (R261X) in exon 10.</p><p><b>CONCLUSION</b>The mutation (R261X) detected in the present study is considered to result in the occurrence of congenital aniridia and cataract in the Chinese family.</p>

Peritoneal equilibration test and results analysis in children undergoing chronic peritoneal dialysis / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore the characteristics of peritoneal transport in children undergoing chronic peritoneal dialysis (PD).</p><p><b>METHODS</b>Peritoneal equilibration test (PET) was carried out 10 times in 6 children (aged from 2 to 14 years) who were maintained by continuous ambulatory peritoneal dialysis (CAPD), and the peritoneal solution transport rate was evaluated by the standards of Twardowski's and Pediatric Peritoneal Dialysis Study Consortium (PPDSC)'s criteria.</p><p><b>RESULTS</b>In this study, the initial PET was performed at (38.7 +/- 15.6) days following initiation of PD, the 4-hours of peritoneal creatinine clearance (4 h-D/P) and glucose absorption (4 h-D/D(0)) was (0.85 +/- 0.24) and (0.34 +/- 0.19), respectively. According to the standards of Twardowski's and PPDSC criteria, the peritoneal transport categories were divided into high transport (H) (6/10), high average transport (HA) (1/10), low average (LA) (3/10) for peritoneal solution transport, and H (3/10), HA (4/10), LA (1/10), low transport (2/10) for glucose absorption. No low transport type of solution was used in the patients. The coincidence rate of peritoneal creatinine and glucose transport types were 100% and 90% between the Twardowski's and PPDSC criteria, respectively. The different changes of peritoneal transport type were found in two patients with continuous PET. The value of 4 h-D/P increased after peritonitis episodes.</p><p><b>CONCLUSION</b>The results showed that the PET in 70% of CAPD children fell into high and high average transport categories elevated by PPDSC's and adult standards, no-sinusoid distribution. The peritoneal solute clearance was adequate in the children, but net water ultrafiltration was lower. Standard pediatric PET and its criteria are consistent with the adult criteria. The capability of peritoneal solute transport increased after peritonitis episodes.</p>

Renal impairment in patients with methylmalonic aciduria: a review of five cases / 中华儿科杂志

<p><b>OBJECTIVE</b>The renal impairment in children with methylmalonic aciduria has seldom been reported. To improve knowledge in this aspect, clinical data of five cases with methylmalonic aciduria with renal involvement were analyzed and the results are reported in this paper, which may be of some help in early diagnosis, treatment and in achieving favorable prognosis.</p><p><b>METHODS</b>Urine methylmalonic acid was measured by gas chromatography-mass spectrometry analysis, if the content exceeded the normal range and vitamin B12 deficiency was excluded, the diagnosis of methylmalonic aciduria was confirmed. Homocysteine in plasma was also measured with fluorescence polarization immunoassay to make sure if concomitant homocysteinemia existed. From January 2002 to January 2005, five patients who had renal impairment were diagnosed as methylmalonic aciduria by urinary organic acid analysis. Among them, three were male, two were female, aged from seven months to 26 years, with average of 13 years. Three were presented to pediatric nephrology clinic with hematuria, proteinuria or edema, the other two were presented to pediatric neurology clinic first for psychomotor retardation. Their clinical features, laboratory findings, treatment regimens and prognosis were analyzed and summarized.</p><p><b>RESULTS</b>All the five patients with methylmalonic aciduria were found to have various degrees of renal impairment, manifested as hematuria or proteinuria. Among them, two cases had gross hematuria and three had microscopic hematuria. Edema was found in two cases and hypertension occurred in one case. Early indicators of renal damage, such as microalbunminuria, N-acetyl-beta-D glucosaminidase, transferrin and alpha-microglobulin showed glomerular and tubular dysfunction. Clinically nephrotic syndrome was diagnosed in one case, the other four cases were diagnosed as glomerulonephritis, and two cases had renal failure. Renal biopsy was performed in one case, tubulo-interstitial damage and mesangial proliferation appeared. Mental retardation and psychomotor disorder were chief nervous system complaints. Leukodystrophy was the main finding on imaging. Megaloblastic anemia was found in three cases. All the five patients were cobalamin-responsive type. Renal impairment was alleviated following treatment, edema and gross hematuria as well as hypertension disappeared later, proteinuria diminished, renal function improved, central nervous system symptoms and hematopoietic function ameliorated.</p><p><b>CONCLUSION</b>In patients with hematuria, proteinuria or renal failure of unknown origin, metabolic screening and urinary organic acid analysis should be performed as early as possible to confirm the diagnosis.</p>

Clinicopathological analysis of IgA nephropathy with crescentic formation in childhood / 中华儿科杂志

<p><b>OBJECTIVE</b>To understand the clinical and pathological characteristics of IgA nephropathy (IgAN) with crescentic formation in children.</p><p><b>METHODS</b>Clinicopathological data of 29 children with IgAN accompanied by crescents were analyzed. These patients were divided into two groups according to the percentage of glomeruli affected by crescents more or less than 50%, and their data were compared.</p><p><b>RESULTS</b>(1) CLINICAL FEATURES: all the patients had hematuria and proteinuria, and macrohematuria (86%) and proteinuria were also common, protein excreted in urine was more than 1 g per day in 76% of the patients. The patients with edema, hypertension, and renal insufficiency were less than fifty percent. Nine patients in Group A (glomeruli affected by crescents > or = 50%) were crescentic IgAN. Significantly more cases in Group A had persistent macrohematuria, hypertension and renal failure than in Group B (glomeruli affected by crescents < 50%) (P < 0.05), with especially severe proteinuria (P < 0.01). It was easy to find nephritic syndrome in Group A, and asymptomatic hematuria combined with proteinuria in Group B. (2) Renal pathology: the glomeruli were affected by crescents from 5% to 85%. There were 52% to 85% in Group A, and 5% to 40% in Group B. Most crescents were cellular. All the cases had a diffuse mesangial proliferation and tubular-interstitial injury to different degree. Three cases had crescentic IgAN. Glomerulosclerosis was significantly more often seen in Group A (P < 0.05) and tuft adhesion was more frequently seen in Group B (P < 0.05). (3) Immunofluorescence: All the patients presented deposition of IgA, IgM and C3. There were 45% specimens combined with the deposition of IgG. Five cases showed 'full house' (17%), four of them were in Group A. None had IgA deposition alone.</p><p><b>CONCLUSION</b>The main clinical feature of IgAN with crescentic formation were hematuria combined with proteinuria, especially persistent gross hematuria and severe proteinuria. All of them showed diffuse mesangial proliferation and tubular-interstitial injury in morphology of kidney. Most of them had tuft adhesion. The main type of immunofluorescence were IgA + IgM and IgA + IgM + IgG deposition. Some showed 'full house' phenomenon. The clinical manifestation and renal lesions of IgAN with diffuse crescentic formation were worse than IgAN with glomeruli affected by crescents < 50%.</p>

Clinical and pathological characteristics of focal segmental glomerulosclerosis in children / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the clinical and pathological characteristics of focal segmental glomerulosclerosis (FSGS) in children.</p><p><b>METHODS</b>The data of 38 children,aged from one and half to 15 years, 25 boys and 13 girls, with primary FSGS were studied retrospectively.</p><p><b>RESULTS</b>Majority of the cases in this study were school-aged children. The average age of initial onset was 8.9 +/- 3.68 years. The ratio of boys to girls was 1.92. The clinical manifestation included isolated proteinuria in 3 cases, proteinuria and hematuria in 1 and nephrotic syndrome in 34 (simple type in 16 and nephritic type in 18). Of 38 cases, 24 (63%) presented with hematuria, 11 (29%) with hypertension and 7 (18%) with decreased creatinine clearance. The pathologic classification included perihilar variant in 17 cases, peripheral variant in 14 and tip variant in 7. The predominant clinical feature of children with tip variant was simple type of nephrotic syndrome (86%). Microscopic hematuria was not common (29%). Blood pressure and renal function were normal. The children with diffuse mesangial hypercellularity superimposed on changes of FSGS (in 21 of 38 cases) were more likely to have hematuria (76%) and less simple nephrotic syndrome (30%). The initial treatment response to prednisone in 34 cases with nephrotic syndrome showed sensitive in 12 cases, resistant in 21 and unknown in 1. Transition from sensitive to resistant occurred in six of 12 children. Three of 4 cases with non-nephrotic syndrome showed no response and the remaining one had unknown response. It was found that 44% of children who received cyclophosphamide and 83% of children who received pulse methylprednisolone and pulse cyclophosphamide or cyclosporin A in addition to oral steroids had complete or partial remission. Correlation analysis showed that the level of proteinuria after treatment was correlated directly with renal tubulointerstitial lesion and renal function (Pr = 0.48, P < 0.05; Pr = 0.45, P < 0.05).</p><p><b>CONCLUSION</b>FSGS was common in school-aged children. The predominant presenting feature was nephrotic syndrome. Hematuria was common. Hypertension and renal insufficiency were less frequently seen. The renal biopsy showed multiple variants. Pulse methylprednisolone and pulse cyclophosphamide or cyclosporin A treatments showed relatively good response.</p>

Clinical significance of antiphospholipid antibody in pediatric patients and review of literature / 中华儿科杂志

<p><b>OBJECTIVE</b>Antiphospholipid antibody (APL) is a particularly important laboratory diagnostic criterion for antiphospholipid syndrome (APS). The significances of positive APL in childhood are seldom reported nor fully understood. The purpose of this study was to analyze 13 cases with positive APL seen in our hospital and to study the relationship between the positive rates of APL and various clinical diseases especially systemic lupus erythematosus (SLE) in order to improve the clinical diagnoses and treatment level of APS in children.</p><p><b>METHODS</b>The clinical data collected from 2000 to 2002 of 13 hospitalized children with positive APL were retrospectively evaluated. Enzyme linked immunosorbent assay (ELISA) and indirect immunofluorescence technique were used respectively to detect APL and antineutrophil cytoplasmic autoantibodies (ANCA) of sera from those children. Other various indexes were also detected according to different characteristics of different diseases.</p><p><b>RESULTS</b>Eight cases had SLE; 2 had acute post-streptococcal infections. The other 3 cases did not show any evidences of primary diseases; they probably had primary APS. SLE was the most common primary diseases to cause development of APL and the cases with SLE showed more severe cutaneous vasculitis than SLE patients who were negative for APL. There was no significant relationship between the positive rates of APL and that of ANCA. Eight APL positive cases complicated with thrombocytopenia and bleeding were treated with high dosage of immunoglobulin [400 mg/(kg.d), for 3 - 5 d] intravenously; the clinical conditions of these cases were ameliorated soon. While the 5 cases who had thrombotic vasculitis and thromboembolism were treated with anticoagulant and antithrombotic therapy with low molecular weight heparin [50 - 100 U/(kg.d)], which led to good clinical effects.</p><p><b>CONCLUSIONS</b>The clinical manifestations of children positive for APL were somehow different from those of adults. Positive APL itself may be nonspecific, it can occur from different causes of diseases. APL detection may be useful to suggest anticoagulant and/or antithrombosis therapy. Treatments for APS should be variable according to different causes and severity of diseases, in the cases of thrombocytopenia and bleeding, high dose intravenous immunoglobulin should be given as soon as possible, while in the cases of thrombotic vasculitis and thromboembolism, anticoagulant and antithrombotic therapy should be given soon.</p>

Analysis of 1268 patients with chronic renal failure in childhood: a report from 91 hospitals in China from 1990 to 2002 / 中华儿科杂志

<p><b>OBJECTIVE</b>Chronic renal failure (CRF) of childhood is not rare. The prognosis of CRF is very poor because of severe systemic complications. A nation-wide survey was conducted and data of hospitalized children (younger than 14 years old) with CRF during the period of 1990 to 2002 were analyzed. The aim was to investigate the epidemiology, natural history, clinical-pathological characteristics, treatment and outcome of the hospitalized children with CRF.</p><p><b>METHODS</b>Questionnaires concerning children with CRF were designed and distributed to the doctors of 91 hospitals in China. The criterion of CRF was creatinine clearance (CCr) < 50 ml/(min x 1.73 m(2)). The data were collected and analyzed.</p><p><b>RESULTS</b>From January 1, 1990 to December 31, 2002, 1658 hospitalized children were diagnosed as CRF. The average annual cases of childhood CRF accounted for 1.31% (ranged from 0.72% to 1.75%) of the hospitalized cases with urologic-kidney diseases. In a comparison between 1990 - 1996 and 1997 - 2002, there were significant increases in the average annual number of cases of childhood CRF and the case ratio of CRF to urologic-kidney diseases (82 +/- 27 vs. 181 +/- 45 and 0.98 +/- 0.21 vs. 1.56 +/- 0.17, respectively, P < 0.001). Complete records were available for 1268 patients. The male to female ratio was 1.49:1. The mean age at the disease onset was 8.18 years. The mean duration of pre-diagnosis of CRF was 2.53 years. In this study, the main primary renal diseases causing CRF were chronic glomerulonephritis and nephrotic syndrome (52.7%). One-fourth of all cases had congenital and hereditary renal diseases, and the majority were renal hypoplasia and dysplasia. The main manifestations of CRF were anemia, gastrointestinal disorders, edema, hypertension and growth retardation. The mean serum creatinine and BUN were 594.7 micromol/L and 39.1 mmol/L, respectively. The cases with renal function >or= grade IV accounted for 80% of all cases. By renal ultrasound scanning, one-third of CRF children were found to have renal atrophy and a part of patients had cystic disorder. Most of the cases received conservative treatment. Dialysis therapy (including 66.5% of hemodialysis and 33.5% of peritoneal) was given to 15.8% of the patients. Twenty-nine cases received renal transplantation. The rate of graft survival was 93.1%. Follow-up was carried out for to 230 cases, the mean duration of follow-up was 2.36 years. One hundred and sixty-seven patients died during hospitalization over the 13-year review period. The main causes of death were cardiac failure and infections in addition to uremia.</p><p><b>CONCLUSION</b>The incidence of CRF in children showed an increasing trend year after year. The main age of onset of the disease was school-age. The main primary renal diseases causing CRF were acquired renal diseases. Conservative treatment was the main therapy of CRF, but renal replacement therapy was initiated in some of the cases. The obvious difference between follow-up cases and lost cases warrants the need to establish a management system of childhood CRF.</p>

A novel mutation of NPHS2 identified in a Chinese family with steroid-resistant nephrotic syndrome / 中华儿科杂志

<p><b>OBJECTIVE</b>Autosomal recessive steroid-resistant nephrotic syndrome (SRNS) is a subgroup of familial nephrotic syndrome. A causative gene has been identified, that is NPHS2, in chromosome 1q25-31, which encodes podocin. This study aimed to detect NPHS2 mutation in a Chinese family with SRNS.</p><p><b>METHODS</b>Renal biopsy was performed on the proband and her sibling for routine histologic and immunohistochemical investigation and electron microscopic examination. The expressions of podocin, nephrin, alpha-actinin and WT1 in glomeruli of the proband were detected by indirect immunofluorescence. Peripheral blood samples were collected for genetic analysis from the proband and her parents, and 53 adults with normal urinalysis. Genomic DNA was isolated from peripheral blood leucocytes. Eight exons of NPHS2 were amplified by polymerase chain reaction. Mutational analysis was performed using denaturing high-performance liquid chromatography (DHPLC) and DNA fragments with aberrant elution profiles of both strands revealed by DHPLC were re-amplified and sequenced directly.</p><p><b>RESULTS</b>The histologic findings on kidney biopsies were focal segmental glomerulosclerosis. In controls, the distribution of staining with P35, rabbit against a human podocin recombinant protein (amino acids 135 - 383 = all the C-terminal part of the protein downstream the transmembrane domain), and P21, rabbit against a human podocin recombinant protein (amino acids 15 - 89 = all the N-terminal part of the protein upstream the transmembrane domain) showed a linear pattern along glomerular capillary walls on glomeruli, and the fluorescent intensity of the staining with P35 was intensely positive. The fluorescent intensity of the staining with P21 was positive. In the proband, the distribution of the staining with P35 showed uneven and nonlinear, and the fluorescent intensity of the staining with P35 was weakly positive. The staining with P21 was negative. The area, location, distribution and fluorescent intensity of the staining with nephrin, alpha-actinin and WT1 on glomeruli of the proband were the same as those in the controls. The DHPLC elution profiles of exon 4 of NPHS2 from the proband and her parent were aberrant. The chromatograms by sequencing detected in the exon 4 of NPHS2 showed a composite heterozygous mutation of both 467_468insT and 503G > A in the proband, a heterozygous mutation of 503G > A in her father, and a heterozygous mutation of 467_468insT in her mother, respectively.</p><p><b>CONCLUSION</b>The study demonstrated for the first time a novel mutation, 503G > A, of NPHS2 in Chinese kindred with autosomal recessive SRNS. A significantly decreased or negative expression was also revealed in glomeruli of the proband stained with two kinds of anti-podocin antibodies.</p>

Antineutrophil cytoplasmic autoantibody positive vasculitis induced by propylthiouracil: a case report / 中华儿科杂志

<p><b>OBJECTIVE</b>Propylthiouracil (PTU) as a drug used during the treatment of hyperthyroidism could induce antineutrophil cytoplasmic autoantibody-positive vasculitis. Here the author reported a childhood case of antineutrophil cytoplasmic autoantibody-positive vasculitis induced by PTU, which is rarely described.</p><p><b>METHODS</b>The diagnosis was made according to the symptoms, signs, serum markers and renal biopsy, and the relevant literature was reviewed.</p><p><b>RESULTS</b>The 12-year-old girl presented with gross hematuria, proteinuria, renal function damage [Ccr 52.46 ml/(min. 1.73 m(2))], positive antineutrophil cytoplasmic autoantibody (ANCA-MPO) (MPO ELISA 140%) and a vasculitis lesion in the renal biopsy sample. She had been treated with PTU for 5 years because of Graves disease. After the diagnosis, the PTU was withdrawn, and prednisone (40 mg/d) and cyclophosphamide (25 mg, Bid) were applied. Three weeks after the therapy with prednisone and cyclophosphamide the gross hematuria disappeared. Three months after the treatment the renal function returned to normal [Ccr 124 mg/(min.1.73 m(2))], and the titer of ANCA-MPO decreased from 140% to 57%.</p><p><b>CONCLUSION</b>PTU may induce antineutrophil cytoplasmic autoantibody positive vasculitis. A right diagnosis and treatment can improve its prognosis of the disease.</p>

Clinical and Pathological Analysis of 91 Children with Lupus Nephritis / 实用儿科临床杂志

Objective To analyze the clinical and pathological characteristics of children with lupus nephritis(LN).Methods Ninety-one children with LN were diagnosed from 1993 to 2005,according to the clinical literature and renal pathology and the data were retrospectively summarized.Results Within the cohort of 91 children,there were 69 females and 22 males(female to male ratio 3.1).Most of the sick children were at the school age ranging from 6.0 to 15.5 years old.Nephrotic syndrome(44.0%) was the most common clinical manifestation.Fifty-nine renal biopsies were performed.Class Ⅳ LN(59.3%) was the most frequent pathological findings."A full-house pattern" on immunofluorescence was found in 72.0% of biopsies.The clinical and pathological manifestations of some children were atypical.There were 3 patients characterized by predominant deposits of immunoglobulin M(IgM),1 patient with predominant deposits of IgA,and 2 children with pauci-immune LN.Three children with class Ⅱ LN in our study presented with nephrotic syndrome.LN was initially controlled by aggressive treatment in 93.7% of thse patients.Relapses of nephritis covered 27.1% of them,mostly caused by the intermittent treatment.Conclusions The clinical and pathological manifestations of LN were variable.Some atypical LN was considered to be associated with the distinct pathogenesis.Most of LN could be controlled by aggressive treatment.Long and regular treatment is necessary to improve the prognosis of LN.

Analysis on association of glucocorticoid receptor gene polymorphism with steroid-resistance in idiopathic nephrotic syndrome of children / 中华儿科杂志

<p><b>OBJECTIVE</b>The nephrotic syndrome is defined by heavy proteinuria, edema, hypoalbuminemia, and hyperlipidemia. Idiopathic nephrotic syndrome (INS) mainly occurs in children, which is generally treated with glucocorticoids. The majority of patients are steroid-sensitive (SSINS) while steroid-resistance occurs in a subset of NS children (SRINS). Although intensive efforts have been undertaken to study the associations between SRINS and renal pathological changes, pharmacokinetics, and the GR density and binding affinity, the mechanisms underlying steroid-resistance are still not elucidated entirely. The authors hypothesized that it might be associated with polymorphisms in the glucocorticoid receptor gene (NR3C1). The study aimed to screen the NR3C1 gene for polymorphisms in genomic DNA samples from SRINS, SSINS children and control group, and to analyze the association of the polymorphisms in the NR3C1 gene and SRINS of children.</p><p><b>METHODS</b>Totally 39 SRINS and 67 SSINS children (81 males and 25 females with the mean age of 7 years) were involved in the study. Umbilical cord blood of 62 normal neonates and peripheral blood of 2 healthy volunteers were selected as controls. Genomic DNA was isolated from peripheral blood lymphocytes of all subjects. All the NR3C1-coding exons and intron-flanking portions were amplified by polymerase chain reaction (PCR). For polymorphism screen, PCR products were analyzed by denaturing high performance liquid chromatography (DHPLC). DNA fragments with aberrant elution profiles were re-amplified and sequenced directly.</p><p><b>RESULTS</b>Twelve aberrant elution profiles were identified with DHPLC in SRINS, SSINS and controls. Among them, 6 previously reported polymorphisms and 6 novel polymorphisms were confirmed by sequencing (198G > A, 200G > A, IVSD-16G > T, 1896C > T, 2166C > T, 2430T > C; novel, 1206C > T, 1374A > G, IVSG-68_IVSG-63delAAAAAA, 2193T > G, IVSH-9C > G, 2382C > T), and 3 groups of SNPs were in complete linkage disequilibrium, which resulted in 3 different haplotypes ([198G > A + 200G > A], [1374A > G + IVSG-68_IVSG-63delAAAAAA + IVSH-9C > G + 2382C > T], [1896C > T + 2166C > T + 2430T > C]). The last two genotypes were first reported. The genotype frequencies of the 2 novel haplotypes were 10.3% vs 1.5% in SRINS and SSINS, and 15.4% vs 7.5% in SRINS and SSINS, respectively. Other polymorphisms were relatively rare detectable both in patients and controls.</p><p><b>CONCLUSION</b>Twelve polymorphisms in the NR3C1 gene were detected with the technique of DHPLC, of which six polymorphisms were identified at the first time. Two types of newly found haplotypes were associated with steroid-resistant idiopathic nephrotic syndrome of children, which might be responsible for steroid-resistance in partial idiopathic nephrotic syndrome of children.</p>

Clinificance of Cystatin C as to Determine Glomerular Filtration Rats / 实用儿科临床杂志

80 mL/ min were 12 cases;minor lesion group(50