Clinical diagnostic techniques for rare genetic diseases in children: current status, advances, and thoughts / 中国当代儿科杂志

Rare diseases refer to a group of single diseases with low incidence rates, complex pathogeneses, severe disease conditions, and rapid progression. Most rare diseases have a genetic background and may occur in childhood. Paying attention to the rare genetic diseases in children and performing early diagnosis and treatment can effectively delay the course of disease and improve the quality of life of children. Many rare diseases can be diagnosed with the help of various experimental techniques, but the diagnosis of rare diseases is still not widely understood. This article summarizes the laboratory diagnostic techniques currently used for rare genetic diseases in children, so as to provide clues for the diagnosis and treatment of such diseases and help to enhance the theoretical understanding and precise medical treatment of rare genetic diseases in children.

Expression of adipokines in children with primary nephrotic syndrome and its association with hyperlipidemia / 中国当代儿科杂志

OBJECTIVES@#To study the expression of adipokines in children with primary nephrotic syndrome (PNS) before and after treatment and its correlation with blood lipids, as well as the role of adipokines in PNS children with hyperlipidemia.@*METHODS@#A total of 90 children who were diagnosed with incipient PNS or recurrence of PNS after corticosteroid withdrawal for more than 6 months were enrolled as subjects. Thirty children who underwent physical examination were enrolled as the control group. Venous blood samples were collected from the children in the control group and the children with PNS before corticosteroid therapy (active stage) and after urinary protein clearance following 4 weeks of corticosteroid therapy (remission stage). ELISA was used to measure the levels of adipokines. An automatic biochemical analyzer was used to measure blood lipid levels.@*RESULTS@#Compared with the control group, the children with PNS had a significantly lower level of omentin-1 in both active and remission stages, and their level of omentin-1 in the active stage was significantly lower than that in the remission stage (@*CONCLUSIONS@#Omentin-1 may be associated with disease activity, dyslipidemia, and proteinuria in children with PNS. Blood lipid ratios may be more effective than traditional blood lipid parameters in monitoring early cardiovascular risk in children with PNS.

Cystinosis induced by / 中国当代儿科杂志

A boy, aged 1 year and 6 months, was found to have persistent positive urine glucose at the age of 4 months, with polydipsia, polyuria, and growth retardation. Laboratory examinations suggested that the boy had low specific weight urine, anemia, hypokalemia, hyponatremia, hypomagnesemia, metabolic acidosis, glycosuria, acidaminuria, increased fractional excretion of potassium, and decreased tubular reabsorption of phosphate. X-ray examinations of the head, thorax, and right hand showed changes of renal rickets. The slit-lamp examination showed a large number of cystine crystals in the cornea. The genetic testing showed a suspected pathogenic homozygous mutation of the

Clinical features of nephrotic syndrome accompanied by eosinophilia in children / 中国当代儿科杂志

OBJECTIVE@#To study the clinical features of nephrotic syndrome (NS) accompanied by eosinophilia in children.@*METHODS@#A retrospective analysis was performed for the clinical manifestations, laboratory findings and treatment outcomes of 18 cases of eosinophilia (15 children, 3 of whom also had eosinophilia at the second recurrence) in children with NS.@*RESULTS@#Of the 18 cases, 16 (89%) had mild eosinophilia, 1 (6%) had moderate eosinophilia, and 1 (6%) had severe eosinophilia. Twelve cases (67%) developed eosinophilia in winter and spring. Nine cases (50%) had infectious diseases: pneumonia (including 2 cases of Mycoplasma pneumonia) in 4 cases, EB virus infection in 3 cases, suspected pinworm infection in 1 case, and Streptococcal infection in 1 case. Five cases (28%) had allergic diseases: urticaria in 2 cases, allergic rhinitis in 2 cases and eczema in 1 case. There was no significant correlation between eosinophil count and the levels of urinary protein, serum albumin and cholesterol (P>0.05). In 8 cases of newly diagnosed NS, urinary protein turned negative within 4 weeks after glucocorticoid treatment. In 10 cases of recurrent NS, urinary protein turned negative in 9 cases after the adjustment of glucocorticoid treatment. In 1 case of recurrent NS (moderate eosinophilia with allergic rhinitis), symptomatic relief and negative urinary protein were achieved after anti-allergic treatment. Glucocorticoid therapy was not administered again in the patient, and the eosinophil count was reduced to a slight increase. The eosinophil counts of the other 17 cases returned to normal.@*CONCLUSIONS@#NS with eosinophilia in children occurs mostly in winter and spring. This disorder is associated with infection or allergic diseases. There was no significant correlation between eosinophil count and the levels of urinary protein, serum albumin and cholesterol.

Discussion on diagnostic value of urinary neutrophil gelatinase-associated lipocalin in the diagnosis of acute pyelonephritis in children / 天津医药

Objective To explore the diagnostic value of urine neutrophil gelatinase-associated lipocalin (NGAL) in children with acute pyelonephritis. Methods A total of 104 children with urinary tract infection admitted to Tianjin Children's Hospital from December 2016 to May 2017 were selected in this study, including 61 cases with acute pyelonephritis (group APN) and 43 with lower urinary tract infection (group non-APN). The serum levels of beta 2-Microglobulin (β2-MG), cystatin C (CysC), C-reactive protein (CRP), procalcitonin (PCT) and urine levels of NGAL were compared between two groups.Receiver operating characteristic(ROC)curves were drawn to evaluate the diagnostic values of serum β2-MG,CysC,CRP,PCT and urine NGAL.Results The serum levels of CRP,PCT,β2-MG and urinary NGAL were significantly higher in APN group than those in non-APN group (P < 0.05). There was no significant difference in serum CysC level between two groups(P>0.05).The areas under the ROC curve(AUC)for serum CRP,PCT,and urinary NGAL were 0.838,0.898 and 0.963.The optimal cutoff value of serum CRP was 22.6 mg/L,the sensitivity was 75.4% and the specificity was 83.7%. The optimal cutoff value of serum PCT was 0.285 μg/L, the sensitivity was 77.0% and the specificity was 93.0%.The optimal cutoff value of urine NGAL was 473 μg/L,the sensitivity was 82.0% and the specificity was 97.7%.Conclusion Urinary NGAL has high diagnostic value for APN in children,and which is helpful for the early identification of APN.

Clinical analysis of 15 851 children at risk of inherited metabolic diseases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To explore the value of urine gas chromatography-mass spectrometry (GC-MS) in the screening of children at risk of inherited metabolic diseases (IMD), and to identify the disease spectrum of IMD and the clinical characteristics of children with IMD.</p><p><b>METHODS</b>The clinical data of 15 851 children at risk of IMD who underwent urine GC-MS in the Tianjin Children's Hospital between February 2012 and December 2016 were retrospectively analyzed.</p><p><b>RESULTS</b>In the 15 851 children, 5 793 (36.55%) were detected to have metabolic disorders. A total of 117 (0.74%) children were confirmed to have IMD, including 77 cases of methylmalonic acidemia (65.8%). The clinical manifestations of confirmed cases in the neonatal period mainly included jaundice, metabolic acidosis, abnormal muscular tension, feeding difficulty, poor response, and lethargy or coma. The clinical manifestations of confirmed cases in the non-neonatal period mainly included delayed mental and motor development, metabolic acidosis, convulsion, recurrent vomiting, and anemia.</p><p><b>CONCLUSIONS</b>GC-MS is an effective method for the screening for IMD in children at risk. Methylmalonic acidemia is the most common IMD. The clinical manifestations of IMD are different between the confirmed cases in the neonatal and non-neonatal periods.</p>

Advances in clinical research on C1q nephropathy / 中国当代儿科杂志

C1q nephropathy is a rare type of glomerulonephritis manifested as the deposition of C1q in the glomerular mesangium during immunofluorescent staining. Systemic lupus erythematosus and type I membranoproliferative glomerulonephropathy need to be excluded in the diagnosis of C1q nephropathy. C1q nephropathy has various manifestations under a light microscope, mainly including minimal change disease, focal segmental glomerulosclerosis, and proliferative glomerulonephritis. This disease is mainly manifested as persistent proteinuria or nephrotic syndrome and occurs more frequently in boys. Currently, glucocorticoids are mainly used for the treatment of this disease. Patients with C1q nephropathy show a good response to immunosuppressant treatment, but have a high rate of glucocorticoid resistance. Therefore, in this case, methylprednisolone pulse therapy or a combination with immunosuppressant treatment helps to achieve a good prognosis.

Value of determination of haptoglobin and α1-antitrypsin in predicting response to glucocorticoid therapy in children with primary nephrotic syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the value of the determination of serum and urine haptoglobin (HP) and alpha 1-antitrypsin (AAT) in predicting the response to glucocorticoid therapy in children with primary nephrotic syndrome (PNS).</p><p><b>METHODS</b>A total of 84 children with PNS were classified to steroid-sensitive nephrotic syndrome (SSNS) (n=58) and steroid-resistant nephrotic syndrome (SRNS) groups (n=26). Forty healthy children were randomly selected for the control group. HP and AAT levels in blood and urinary samples were determined using ELISA. The efficiency of HP and AAT in predicting the response to glucocorticoid treatment of PNS was evaluated by the receiver operating characteristic (ROC) curve.</p><p><b>RESULTS</b>Compared with the control group, both the SSNS and SRNS groups had significantly higher serum HP concentrations and urine AAT/Cr ratio before treatment (P<0.05); compared with the SSNS group, the SRNS group had significantly higher serum HP concentrations and urine AAT/Cr ratio before treatment and after one week and four weeks of treatment (P<0.05). Serum HP had the highest efficiency in predicting the response to glucocorticoid treatment of PNS at the concentration of 37.935 mg/mL, with the sensitivity and specificity being 92.3% and 86.2% respectively. Urine AAT/Cr ratio had the highest prediction efficiency at 0.0696, with the sensitivity and specificity being 100% and 79.3% respectively. ROC curve analysis of serum HP combined with urine AAT/Cr ratio showed a better prediction efficiency, with the sensitivity and specificity being 92.3% and 96.6% respectively.</p><p><b>CONCLUSIONS</b>The increase in serum HP level or urine AAT/Cr ratio may indicate glucocorticoid resistance in the early stage of PNS. A combination of the two can achieve better efficiency in the prediction of SRNS.</p>

Effect of prednisone on expression of Ezrin and NEPH1 in rats with Adriamycin-induced nephrosis / 中华实用儿科临床杂志

Objective To explore the mechanism of proteinuria and renal protection of prednisone by observing the expressions of Ezrin and NEPH1 in rats with Adriamycin (ADR)-induced nephrosis.Methods The 24 rats were divided into 3 groups,which were control group,model group and prednisone group.ADR model was induced by a tail intravenous injection of ADR for 2 times.Serum index and 24 h urinary protein were measured in 4 and 8 weeks.The expressions of Ezrin and NEPH1 in glomerulus were evaluated by using two-step immunohistochemistry respectively.Results Compared with control group,heavy proteinuria,hypoalbuminemia,hyperlipemia were observed in 4 weeks in the model group and the prednisone group which indicated that the models were successfully established.Compared with model group,in 8 weeks,24 h urinary protein,total cholesterol and serum creatinine in prednisone group were significantly decreased(all P ＜ 0.0 l),while albumin,total protein and endogenous creatinine clearance rate were significantly increased(all P ＜ 0.05) ;The expressions of Ezrin and NEPH1 in model group were significantly decreased compared with control group(all P ＜ 0.01).The expressions of Ezrin and NEPH1 in prednisone group were significantly increased compared with model group(all P ＜0.01).The expressions of Ezrin and NEPH1 were negatively related to proteinuria(r =-0.838,-0.884,all P ＜ 0.01).Conclusions The declined expressions of Ezrin and NEPH1 in rats with ADR-induced nephrosis may be one of mechanisms of proteinuria.Prednisone can reduce the proteinuria and relieve the renal pathological damage by improving the expression of Ezrin and NEPH1.

Significance of joint detection of serum cystatin C, procalcitonin, and urine N-acetyl-β-D-glucosaminidase combined detection on localization diagnosis of the urinary tract infection in children / 中华实用儿科临床杂志

Objective To explore the differences of biological markers level between upper urinary tract infection(UUTI) and lower urinary tract infection(LUTI) in children for providing help for localization diagnosis of urinary tract infection(UTI).Methods One hundred and nine children with UTI hospitalized in Children's Hospital of Tianjin from May 2010 to Jan.2012 were divided into UUTI group (18 cases) and LUTI group (91 cases).The clinical information (sex,age,onset symptoms),laboratory test including blood urea nitrogen and creatinine,biological markers including serum cystatin C(CysC),procalcitonin(PCT),β2-microglobulin (β2-MG),urine microalbumin(mAlb),transferrin (TF),α1-microglobulin (α1-MG),β2-MG and N-acetyl-β-D-glucosaminidase (NAG) were recorded.Then SPSS 17.0 software was used to analyze the data.Results UUTI children showed higher level of serum CysC,PCT,urine mAlb,TF,α1-MG,β2-MG and NAG than LUTI children did.The area under ROC curve of the 7 biological markers were all between 0.71 and 0.87.Logistic regression test was used to do multiple regression analysis and establish the multiple regression model.The standard of eliminating or screening variables was 0.05.CysC,PCT,NAG were identified as influence factors.Combining test result of CysC,PCT,NAG could improve diagnostic value so that the sensitivity could reach 90％ and the specificity could reach 88.9％.Conclusions Both of serum CysC,PCT and urine mAlb,TF,α1-MG,β2-MG,NAG can be used for the positioning diagnosis of UTI,and the diagnostic value of joint test of serum change of CysC,PCT,urine NAG is higher than any single biological marker.

Clinical significance of determining urinary podocalyxin level in children with primary nephrotic syndrome / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the clinical significance of urinary podocyte marker protein podocalyxin (PCX) in the diagnosis of primary nephrotic syndrome (PNS) in children and the evaluation of disease severity.</p><p><b>METHODS</b>PCX levels in the first morning urine were measured by turbidimetric immunoassay (TIA) in 175 children, including 53 children with acute PNS [36 cases of simple nephrotic syndrome (NS) and 17 cases of nephritic NS], 56 children with PNS in the remission stage (relapsed: 42 cases) and 66 healthy children (control group). Twenty-four hour urinary protein was measured in the 53 children with acute PNS. The optimal operating points for the diagnosis of acute PNS and nephritic NS were determined using the receiver-operating characteristic curve (ROC curve).</p><p><b>RESULTS</b>Significant increasd levels of urinary PCX were found in children with acute PNS compared with those in the remission stage and the control group (P<0.01). A positive correlation was found between urinary PCX and 24 hour urinary protein in children with acute PNS (r=0.39, P<0.01). In children with acute PNS, urinary PCX levels were significantly higher in the nephritic NS group than in the simple NS group (P<0.05). In children in the remission stage, a significant increase in levels of urinary PCX was found in children who had relapsed compared with those who had not (P<0.05). The area under the ROC curve for the diagnosis of acute PNS and nephritic NS was 0.915 and 0.784 respectively. The optimal operating point for the diagnosis of acute PNS and nephritic NS was 7.97 and 10.28 ng/mL respectively, with a sensitivity and specificity of 81.1% and 93.4% respectively for acute PNS and of 94.1% and 52.8% respectively for nephritic NS.</p><p><b>CONCLUSIONS</b>The quantitative detection of urinary PCX is useful in the evaluation of podocyte dynamic changes. It is helpful in the diagnosis of acute PNS and in the differentiation of nephritic NS and simple NS.</p>

Spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome complicated by urinary tract infection: an analysis of 97 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome (NS) complicated by urinary tract infection (UTI).</p><p><b>METHODS</b>A retrospective analysis was performed on the spectrum and drug sensitivity of pathogenic bacteria in 97 children with NS complicated by UTI, who hospitalized from January to December, 2011.</p><p><b>RESULTS</b>The incidence of UTI in children with NS was 36.5%. It was significantly more common in children with recurrent NS than in those with primary NS (44.0% vs 31.9%; P<0.05). These cases mainly presented with asymptomatic bacteriuria. Enterococcus was the most common pathogenic bacteria (50.5%), including Enterococcus faecium (29.4%) and Enterococcus faecalis (21.1%), followed by Gram-negative bacteria, such as Escherichia coli (15.6%) and Klebsiella pneumoniae (14.7%). Enterococcus was highly sensitive to nitrofurantoin, vacomycin and linezolid, but was highly resistant to tetracycline and moxifloxacin. More multi-resistant strains were detected in Enterococcus faecium than in Enterococcus faecalis (72% vs 17%; P<0.05). Escherichia coli and Klebsiella pneumoniae were highly sensitive to amikacin, imipenem and piperacillin/tazobactam. Of the Gram-negative bacteria, 25% produced extended spectrum β-lactamases (ESBLs). ESBLs-producing bacteria had 100% sensitivity to imipenem, amikacin and piperacillin/tazobactam but were highly resistant to ampicillin, cefazolin and ceftriaxone.</p><p><b>CONCLUSIONS</b>Children with recurrent NS are more susceptible to UTI than those with primary NS. Enterococcus is becoming major pathogenic bacteria for UTI in children with NS and has relatively high drug resistance, and most strains of Enterococcus faecium are multi-resistant.</p>

Antibiotic resistance of pathogens isolated from 181 children with complicated urinary tract infection / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the distribution and antibiotic resistance of pathogens isolated from children with complicated urinary tract infection.</p><p><b>METHODS</b>A retrospective analysis was performed on the distribution and antibiotic resistance of pathogens isolated from 181 children with complicated urinary tract infection (positive urine culture). The antibiotic resistance of common pathogens was determined by the antimicrobial susceptibility test.</p><p><b>RESULTS</b>Gram-negative bacilli were the main pathogens (63.5%), and involved Escherichia coli (E.coli) of 42.0%. Gram-positive cocci accounted for 32.1%, and involved enterococci faecalis of 15.5%. Fungi infection was found in 4.4% of children. The resistance rate of E.coli to ampicillin was the highest (89.4%), but the rate decreased significantly by adding amoxicillin/clavulanic acid (34.2%). E.coli had a high resistance rate to cephazolin, ceftriaxone and cafalotin (>50%), but the resistance rate of E.coli to cefoperazone/sulbouam was significantly lower than other cephalosporins (P<0.01). E.coli was sensitive to imipenem and displayed a lower resistance rate to furadantin (<10%). The resistance rate of enterococci faecalis to rifampicin was high (78.3%), but was low to furadantin, vancomycin and linezolid (<10%). The multiresistant strains accounted for 77.4% of gram-negative bacilli.</p><p><b>CONCLUSIONS</b>E.coli is the major pathogen in children with complicated urinary tract infection, and the enterococci-caused urinary tract infection has been increasing. These pathogens have a high antibiotic resistance, and most of them are multiresistant. Antimicrobial therapy should be based on the results of urine culture and antimicrobial susceptibility test.</p>

Bacterial pathogens and resistance patterns in community acquired pediatric urinary tract infection: experience of 152 cases / 中国当代儿科杂志

<p><b>OBJECTIVE</b>This study investigated the pathogen distribution and resistance patterns in childhood urinary tract infection in order to provide references for optimal use of antibiotics in the treatment of this disorder.</p><p><b>METHODS</b>The clinical data of 152 children with community acquired urinary tract infection (urinary culture positive) between December 2001 and December 2004 were studied retrospectively. The bacterial pathogens of urinary tract infection and antimicrobial resistance were analyzed.</p><p><b>RESULTS</b>Gram-negative bacilli was predominant pathogenic bacteria, accounting for 79.0% of the cases, and Escherichia coli (E. coli) was most commonly found (56.2%). Gram-positive cocci accounted for 18.4%, including 15.1% of Enterococcus faecalis. Fungi was rarely seen, accounting for only 2.6%. E. coli had a resistance rate of more than 50% to ampicillin, amoxicillin/clavulate, co-trimoxazole, cefradine, and fosomycin, but a very low resistance rate (< 4%) to 3rd generation cefalosporin, nitrofurantoi, azactom and amikacin. Enterococcus faecalis had a low resistance rate (< 20%) to ampicillin, vancomycin, penicillin, and nitrofurantoin.</p><p><b>CONCLUSIONS</b>E. coli is the major pathogen in community acquired pediatric urinary tract infection, and Enterococcus has been become another important pathogen. Selection of antibiotics for the treatment of this disorder should base on drug-sensitive test results.</p>