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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.

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 CTN S gene, C.922g>A(p.Gly308Arg). The boy was finally diagnosed with cystinosis. At the beginning of treatment, symptomatic supportive treatment was given to maintain the stability of the internal environment, and cysteamine tartaric acid capsules were used after diagnosis to remove cysteine. This article reported a case of cystinosis caused by CTNS gene mutation and summarized the etiology, clinical features, diagnosis, and treatment of this disease, which can provide a reference for the early diagnosis, treatment, and subsequent study of the disease.

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 ( P <0.001). For the children with PNS, the level of chemerin in the active stage was significantly higher than that in the remission stage, and the children with PNS in the active stage had a significantly higher level of chemerin than the control group ( P <0.001). For the children with PNS, atherogenic index of plasma, atherogenic coefficient (AC), castelli risk index-1 (CRI-1), castelli risk index-2 (CRI-2), and non-high-density lipoprotein in the active stage were significantly higher than those in the remission stage ( P <0.001), and these indices in the children with PNS in the active stage were significantly higher than those in the control group ( P <0.001). The children with PNS in the remission stage had significantly higher atherogenic index of plasma, AC, CRI-1, and non-high-density lipoprotein than the control group ( P <0.001). Compared with the control group, the children with PNS in the remission stage had significantly higher serum levels of total cholesterol, triglyceride, high-density lipoprotein, low-density lipoprotein, apolipoprotein B, and apolipoprotein A ( P <0.01). In the children with PNS, the ratio of omentin-1 before and after corticosteroid therapy was positively correlated with that of high-density lipoprotein, 24-hour urinary protein excretion, and high-density lipoprotein/apolipoprotein A before and after treatment, and it was negatively correlated with the ratio of AC and CRI-1 before and after treatment ( P <0.05). The PNS children with low omentin-1 levels in the active stage had significantly higher levels of CRI-1, CRI-2, AC, and apolipoprotein B/apolipoprotein A ratio than those with high omentin-1 levels ( P <0.05)., 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.

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.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

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.

Objective: 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)., Methods: 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., Results: 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., Conclusions: 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.

Objective: To investigate the spectrum and drug sensitivity of pathogenic bacteria in children with nephrotic syndrome (NS) complicated by urinary tract infection (UTI)., Methods: 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., Results: 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., Conclusions: 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.

Objective: 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., Methods: 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)., Results: 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., Conclusions: 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.

Objective: To investigate the distribution and antibiotic resistance of pathogens isolated from children with complicated urinary tract infection., Methods: 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., Results: 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., Conclusions: 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.

Background: This report presents a rare patient with cardiac tamponade as the first manifestation of primary gastric signet-ring cell carcinoma., Case Report: A 56-year-old woman with emergent dyspnea, anterior chest oppression, and hypotension was diagnosed as having cardiac tamponade due to massive pericardial effusion. The endoscopic examination of the stomach disclosed gastric cancer in the posterior wall of the antrum and the biopsy showed signet-ring cell carcinoma. The gastric cancer was complicated by malignant pericardial effusion and pleural effusion as well as metastasis to the peripheral lymph nodes and bones. The patient was treated with percutaneous pericardiocentesis followed by systemic chemotherapy (oxaliplatin and sequential 5-fluorouracil plus leucovorin). The pericardial effusion gradually disappeared and there was no cardiac tamponade occurrence. The patient has survived more than 6 months so far., Conclusions: Cardiac tamponade may originate from a primary gastric signet-ring cell carcinoma. Pericardiocentesis followed by systemic chemotherapy may be effective in controlling such advanced gastric signet-ring cell carcinoma.

Objective: 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., Methods: 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., Results: 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., Conclusions: 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.

Objective: To observe the preventive and therapeutic feasibility of heparin calcium injection in rats with focal segmental glomerulosclerosis (FSGS)., Methods: Eighteen male Wistar rats were divided into three groups: Normal control group (A, n=6), heparin-treated rats (B, n=6) and model group (C, n=6). Rat model of FSGS was constructed with low-dose adriamycin, metaraminol and high lipid feed method. Group B was treated with heparin. 24-hour urinary protein was measured at the 0, 2nd, 4th, 6th and 12th week. Serum total protein, albumin, cholesterol, blood urea nitrogen (BUN) and serum creatinine (SCr) were determined at 0, 2nd, 6th and 12th week. Renal cortex blood flow was performed at the 12th week. Renal pathology changes were evaluated at the 12th week as well., Results: 24-hour urinary protein was decreased in heparin treatment group after 6th week. The serum cholesterol level in heparin treatment group was lower than that in model group at 12th week. Renal cortex blood flow was increased significantly in heparin -treated group. Glomerular sclerotic index (SI) and glomerular extracellular matrix (ECM)/glomerular area (GA) were decreased significantly in heparin treatment group. Electron microscopy revealed that there was no glomerular capillary cavities obstruction in heparin -treated group, basement membrane change and foot precesses fusion were markedly alleviated in comparison with model group., Conclusion: Heparin may be play a valuable role in the prevention and treatment of FSGS.