Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province / 中华医学遗传学杂志

Objective@#To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province.@*Methods@#For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes.@*Results@#Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C (18.07%), R243Q (12.05%) and EX6-96A>G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A>G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%).@*Conclusion@#The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.

Characteristics of gene variants among patients with hyperphenylalaninemia from Quanzhou region of Fujian province / 中华医学遗传学杂志

OBJECTIVE@#To explore the spectrum of genetic variants among patients with hyperphenylalaninemia (HPA) from Quanzhou area of Fujian province.@*METHODS@#For 63 children affected with HPA, next generation sequencing was used to identify potential variants in PAH, PTS, PCBD1, QDPR, SPR and GCH1 genes.@*RESULTS@#Fifty two variants underlying phenylalanine hydroxylase deficiency (PAHD) and 13 variants underlying 6-pyruvoyl tetrahydropterin synthase deficiency (PTPSD) were identified. Two patients carried variants of both PAH and PTS genes. The most common variants of the PAH gene were R53H (21.69%), R241C(18.07%), R243Q(12.05%) and EX6-96A to G (7.23%), which were mainly located in exons 7 (32.53%), 2 (21.69%), 6 (9.64%) and 12 (9.64%). The L227M variant of the PAH gene was unreported previously. N52S (35.00%), P87S (25.00%), IVS1-291A to G (10.00%) and T67M (10.00%) variants were the most common variants for the PTS gene and were mainly located in exons 2 (35.00%) and 5 (35.00%).@*CONCLUSION@#The variant spectrum underlying HPA in Quanzhou area showed a geographical specificity. A novel variant of the PAH gene (L227M) has been detected.

Detection of GCDH mutations in five Chinese patients with glutaric acidemia type I / 中华医学遗传学杂志

OBJECTIVE To detect potential mutations of GCDH gene in five patients with glutaric acidemia type I (GA-I). METHODS Genomic DNA was extracted from peripheral blood samples from the patients. The 11 exons and their flanking sequences of the GCDH gene were amplified with PCR and subjected to direct sequencing. RESULTS Four mutations of the GCDH gene were identified among the patients, which included c.532G>A (p.G178R), c.533G>A (p.G178E), c.106_107delAC (p.Q37fs*5) and c.1244-2A>C. Among these, c.1244-2A>C was the most common, while c.106_107delAC was a novel mutation, which was predicted to be pathogenic by MutationTaster software. CONCLUSION The diagnosis of GA-I has been confirmed in all of the five patients. Identification of the novel GCDH mutations has enriched the mutational spectrum of the GCDH gene.

Mutational analysis of ASS1, ASL and SLC25A13 genes in six Chinese patients with citrullinemia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations in six patients with citrullinemia.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples from the patients. Mutations of the ASS1, ASL and SLC25A13 genes were screened using microarray genotyping combined with direct sequencing.</p><p><b>RESULTS</b>One patient was diagnosed with argininosuccinate lyase deficiency, and has carried a homozygous c.1311T>G (p.Y437*) mutation of the ASL gene. The remaining five patients were diagnosed with neonatal intrahepatic cholestasis due to citrin deficiency, and have respectively carried mutations of the SLC25A13 gene including [c.851-854delGTAT+c.851-854delGTAT], [c.851-854delGTAT+IVS6+5G>A], [c.851-854delGTAT+IVS16ins3kb], [c.851-854delGTAT+IVS6-11A>G] and [c.851-854delGTAT+c.1638-1660dup23]. Among these, the c.1311T>G mutation was first identified in the Chinese population, and the IVS6-11A>G mutation was a novel variation which may affect the splicing, as predicted by Human Splicing Finder software.</p><p><b>CONCLUSION</b>This study has confirmed the molecular diagnosis of citrullinemia in six patients and expanded the mutational spectrum underlying citrullinemia.</p>

Mutational analysis of SLC22A5 gene in eight patients with systemic primary carnitine deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the mutations of SLC22A5 gene in patients with systemic primary carnitine deficiency (CDSP).</p><p><b>METHODS</b>High liquid chromatography tandem mass spectrometry (HPLC/MS/MS) was applied to screen congenital genetic metabolic disease and eight patients with CDSP were diagnosed among 77 511 samples. The SLC22A5 gene mutation was detected using massarray technology and sanger sequencing. Using SIFT and PolyPhen-2 to predict the function of protein for novel variations.</p><p><b>RESULTS</b>Total detection rate of gene mutation is 100% in the eight patients with CDSP. Seven patients had compound heterozygous mutations and one patient had homozygous mutations. Six different mutations were identified, including one nonsense mutation [c.760C>T(p.R254X)] and five missense mutations[c.51C>G(p.F17L), c.250T>A(p.Y84N), c.1195C>T(p.R399W), c.1196G>A(p.R399Q), c.1400C>G(p.S467C)]. The c.250T>A(p.Y84N) was a novel variation, the novel variation was predicted to have affected protein structure and function. The c.760C>T (p.R254X)was the most frequently seen mutation, which was followed by the c.1400C>G(p.S467C).</p><p><b>CONCLUSION</b>This study confirmed the diagnosis of eight patients with CDSP on the gene level. Six mutations were found in the SLC22A5 gene, including one novel mutation which expanded the mutational spectrum of the SLC22A5 gene.</p>

Study of the risk factors in disease progression and concentrations of VEGF and VCAM-1 in hand foot and mouth disease combined with encephalitis / 中华微生物学和免疫学杂志

Objective To explore the risk factors in disease progression and the significance of vascular endothelial growth factor ( VEGF ) and vascular intercellular adhesion molecule-1 ( VCAM-1 ) in hand foot and mouth disease ( HFMD) combined with encephalitis .Methods Altogether 92 subjects with HFMD were enrolled in the study and were divided into four groups , including group A ( ordinary group with no complication ) , group B ( severe group with complication ) , group C ( critical group with complication ) , group D ( recovery group with complication ) .Concentrations of VEGF and VCAM-1 in serum and cerebro-spinal fluid were detected by double antibody sandwich ELISA method .Multiple factors logistic regression analysis was performed to analyze main risk factors in disease progression for two combinations , one for ordi-nary group and severe group , the other for severe group and critical group .The results were analyzed by SPSS16.0 statistical software.Results The concentration of VEGF and VCAM-1 in serum and cerebrospi-nal fluid had statistically significant differences among the four groups , but there was no significant difference between group A and group D , and between group B and group C .In addition , the statistically significant factors for prediction of disease progression were duration of fever , limb shaking, cerebrospinal fluid WBC , cerebrospinal fluid protein and EV 71 IgM between ordinary group and severe group , and cerebrospinal fluid WBC, respiratory rate and heart rate between severe group and critical group .The multiple factors logistic regression analysis revealed that limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum were the main risk factors for disease progression from ordinary to severe (P=0.071, 0.019, 0.020, 0.025 and OR=147.629, 26.572, 5.958, 6.345).And increased heart rate indicated the progression from se-vere to critical with P value of 0.001 and OR value of 2.69.Conclusion (1) Compared with group A, VEGF and VCAM-1 in serum and cerebrospinal fluid were highly expressed in patients with HFMD combined with encephalitis .Therefore , VEGF and VCAM-1 could be used as diagnostic criteria for auxiliary diagnosis of encephalitis in patients with HFMD and reflect the severity and prognosis to a certain extent .( 2 ) Risk factors like limb shaking , cerebrospinal fluid protein , VEGF and VCAM-1 in serum would be helpful to early diagnosis of severe patients .Increased heart rate would be a significant factor for identification of patients with critical disease , according to which a timely treatment would be provided to prevent from worse .

Combined application of low-dose dopamine and phentolamine for treatment of edema in children with nephrotic syndrome / 中国小儿急救医学

Objective To explore the efficacy and safety of low dose dopamine combined with phentolamine in the treatment of primary nephrotic syndrome (PNS) with edema. Methods Retrospective control studies were performed in 155 patients of PNS with edema, who received comprehensive treatment with small dose dopamine combined with phentolamine (group A). Patients treated with furosemide infusion were recruited as control (group B). Results The urinary output, urinary sodium increased after therapy in group A, showing significant differences (P ＜ 0. 01). But urinary potassium excretion, serum sodium and potassium showed no significant difference after therapy in group A. The urinary output, urinary sodium and potassium excretion increased and the serum sodium and potassium decreased after therapy in group B, all showing significant differences between before and after treatment (P ＜0. 01). The edema relief rate,urinary output, urinary sodium excretion, serum sodium and potassium in group A was significantly higher whereas urinary potassium excretion were significantly lower than those of group B(P ＜0. 01). The rate of drug adverse reaction in group A was significantly lower than that of group B. Conclusion Low dose dopamine combined with phentolamine in PNS with edema is safe and effective,which may be a substitute of diuretic like furosemide in the treatment of edema of patients with different blood volume.

Laboratory tests and intervention of early renal damage in children with Henoch-Schonlein purpura / 中国小儿急救医学

Objective To investigate the efficacy of laboratory tests in the renal damage early diagnosis of children with Henoch-Schoalein purpura (HSP) and clinical effect of early intervention.Methods For the 143 HSP patients with normal repeated urine routine test findings,renal function biomarkers including urinary proteins ( immunoglobulin G (IgG),micro-albumin ( MA ),transferrin (TRF),a1 -microglobulin ( α1 -MG),β2-Microglobulin (β2-MG) ) and urinary enzymes ( N-acetyl-beta-D-glucosaminidase ( NAG ),γ-glutamyltransferase (y-GT) ) were detected to investigate the details of renal function changes.One hundred and thirty-one HSP patients,who had abnormal laboratory test findings of renal function biomarkers mentioned above,were randomly divided into control group ( n =65 ) and intervention group ( n =66 ),and both groups received comprehensive treatment including cimetidine,loratadine and calcium agents.However,66 patients in intervention group received low-dose heparin via micropump-based continuous intravenous infusion and regular oral diammonium glycyrrhizinate treatment.Sixty-five patients were enrolled in control group,without further treatment.Results Among the 143 patients with normal urine routine examination,131 cases (91.61％ ) had abnormal findings of renal function biomarkers.After therapy either for 2 months or 4 months,urine protein and urine enzymes were lower than before treatment,and the difference was significant (P ＜ 0.01 ).In the control group only β2-MG,NAG,γ-GT3 indexes significantly lowered at the end of 2 months ( P ＜0.01 ),and all parameters were significantly decreased at the end of 4 months ( P ＜0.01 ).Furthermore,Intervention group had lower levels of renal function biomarkers at the end of 2 months or 4 months,as compared with the control group,showing significant difference ( P ＜0.05 or P ＜0.01 ).Urinary IgG,MA,TRF,NAG recovered rapidly in the intervention group after 4 months and almost returned to the normal,but urinary α1-MG,β2-MG,γ-GT recovered slowly and still remained abnormal after 4 months due to the varying severity.After treatment for 4 months,the rate of urine testing abnormalities was higher in the control group than in the intervention group (36.92％ vs 6.10％ ),and the difference was significant (P ＜0.05).Conclusion Combined detection of renal function biomarkers is helpful for early diagnosis of renal damage in HSP patients.Early intervention with heparin and diammonium glycyrrhizinate can prevent kidney damage,delay disease progress.Early diagnosis and early intervention should be emphasized for the treatment strategy of the renal damage of children with HSP.

Low-dose heparin micro-pump continuous regular infusion in the treatment of primary nephrotic syndrome / 中国小儿急救医学

Objective To explore the efficacy and safety of low-dose heparin in the treament of children with primary nephrotic syndrome (PNS). Methods It was an open and comparative trial. Eightyeight children with PNS in the hypercoagulable state,on the basis of administrating with glucocorticosteroid,were administrated with low-dose heparin that infused by micro pump oriented to time ( group A). Eighty patients only treated with glucocorticosteroid were chosen as control (group B). Results Serum-albumin and activated partial thromboplastin time (APTT) increased,but fibrinogen (Fib) decreased after therapy in the group A,and they all showed significant differences (P ＜ 0. 01 ). Serum-albumin increased after therapy in the group B and there was significant difference (P＜0. 01 ). However,APTT and Fib in the group B showed no significant difference( P ＞ 0. 05 ) between post-treatment and pretherapy. Post-treatment serum-albumin and APTT in the group A were significantly higher than those in group B, and Fib was significantly lower than that in group B ( P ＜ 0. 01 ). The rate of urine protein remission in group A (82/88) was significantly higher than that in group B (63/80). Urine protein remission time and edema disappearance time were significantly shorter in group A than group B ( P ＜ 0. 01 ). APTT of group A at the peak concentration of heparin after therapy was significantly higher than that of pretherapy ( P ＜ 0. 01 ), and the ratio was 2. 38. However, there was no significant difference in APTT at the valley concentration of heparin between post-treatment and pretherapy ( P ＞ 0.05 ). Conclusion Low dose-heparin infused by micro pump oriented to time in the treatment of children with PNS has an obvious anticoagulative effect. It can improve the rate of urine protein remission and shorten edema disappearance time. Meanwhile it is safety ,requires no laboratory monitor and has few drug side effects,thus it deserves further clinical application.