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1.
Article in Chinese | WPRIM | ID: wpr-907315

ABSTRACT

Hepatolenticular degeneration, also known as Wilson disease(WD), is an autosomal recessive disease with copper excretion disorder caused by ATP7B gene mutation.At present, the global incidence of hepatolenticular degeneration is about 1/30 000, but the frequency of ATP7B gene mutation is about 1/90.WD mainly manifests clinically as acute and chronic liver disease, neurological damage and renal impairment, etc.It is a genetic disease that can be well controlled by early diagnosis and treatment, so early diagnosis and treatment are important.However, because of its complex genotype and phenotype, it is easy to be misdiagnosed and delayed treatment.There is no single diagnostic standard for diagnosis of WD at the moment.The Leipzig diagnostic scoring system is often used for diagnosis.In recent years, there has been a new supplement to the diagnostic methods of WD.Some studies have confirmed that measuring the concentration of ATP7B protein by using ATP7B peptide can be used as a new diagnostic method for hepatolenticular degeneration, which is helpful for early accurate diagnosis.

2.
Article in Chinese | WPRIM | ID: wpr-885524

ABSTRACT

Objective:To investigate the treatment and prognosis of children with propionic acidemia (PA).Methods:This study involved 82 children with PA treated in the Department of Pediatric Endocrinol-ogy and Genetic Metabolism, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine from December 2002 to June 2020. Clinical data, including manifestations, laboratory test results, treatment strategy, and follow-up data, were summarized and analyzed using t-test or Mann-Whitney U test. Results:(1) Among the 82 cases consisting of 50 (61.0%) boys and 32 (39.0%) girls, 59 (72.0%) were diagnosed after clinical onset; 22 (26.8%) were diagnosed by newborn screening, including eight asymptomatic ones; the other one (1.2%) was asymptomatic but confirmed after the diagnosis of PA in the patient's sibling. The average age at first onset was 4.5 months (2 d-5 years) in 73 subjects, of which 28 (38.4%) were early-onset PA (within three months after birth). (2) Cranial MRI was performed on 26 cases, and abnormality was identified in 19 (73.1%) cases. (3) Hyperlactatemia was found in 16 cases among 30(53.3%) who underwent relevant examination with the average lactic acid level of 3.5 (2.1-4.3) μmol/L, while 35 out of 40 patients (87.5%) had hyperammonemia with an average blood ammonia level of 105.4 (34-907) μmol/L. (4) Among the 28 early-onset PA cases, 16 (57.1%) died, and 12 (42.9%) survived. There was no significant difference in the serum propionylcarnitine level, propionylcarnitine to acetylcarnitine ratio, urine 3-hydroxypropionic acid, or methylcitrate level between the survival and death cases. (5) Genetic mutations were detected in 75 patients (91.5%), among which 26 (34.7%) carried PCCA gene mutations and 48 (64%) with PCCB gene mutations. One patient (1.3%) harbored one known pathogenic mutation in each of the PCCA and PCCB genes. All mutations were inherited from the parents. (6) Followed up to June 2020, 57 (69.5%) patients survived, and 25 (30.5%) died from multiple organ failure secondary to severe acidosis, including 16 early-onset and nine late-onset cases. Conclusions:The primary treatment of PA is dietary control. Most PA patients are diagnosed after clinical onset, but symptoms may recur and even have developmental retardation despite treatment. Some of those diagnosed through newborn screening are asymptomatic after treatment. Newborn screening using tandem mass spectrometry is recommended for early diagnosis and treatment of PA.

3.
Article in Chinese | WPRIM | ID: wpr-513580

ABSTRACT

Objective To investigate the clinical and biochemical metabolic features of 12 patients with systemic primary carnitine deficiency(CDSP) and to identify the SLC22A5 gene mutation types of the disease. Method The clinical and biochemical data were collected by retrospective analysis. DNA direct sequencing and multiplex ligation dependent probe amplification(MLPA)were applied for SLC22A5 gene analysis. Result Among 12 patients with CDSP, 3 cases had evident infection factors, 6 cases with convulsions, 5 cases manifested liver hypertrophy, 8 cases with hyperammonemia, and 9 cases showed myocardial damage. All CDSP patients were detected biallelic pathogenic mutation in SLC22A5 gene by direct sequencing. The gene types include IVS2+1G>T, c.3G>T(p.Met1Ile), c.760C>T(p.Arg254X), c.1400C>G(p.Ser467Cys), c.844dupc(p.Arg282fs), c.338G>A(p.Cys113Tyr), c.51C>G(p.Phe17Leu), c.659A>T(p.Glu220Val), and c.1365dupC(p.Thr456fs). c.659A>T(p.Glu220Val) and c.1365dupC(p.Thr456fs)are novel mutations. One female patient was maternal CDSP, her child had abnormal newborn screening. The allele frequency of c.760C>T(p.Arg254X) and c.1400C>G(p.Ser467Cys) were 37.5%(9/24)and 29.2%(7/24)respectively. The MLPA test results of all patients were negative. Conclusion The clinical manifestations are complex and various in patients with CDSP. Point and small InDel(insertions/deletions)mutation constitute the major alteration in SLC22A5 gene. c.1400C>G(p.Ser467Cys) might be another prevalence mutation type in Chinese CDSP patient.

4.
Article in Chinese | WPRIM | ID: wpr-335149

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical and molecular features of a child with carnitine palmitoyltransferase 1A (CPT1A) deficiency.</p><p><b>METHODS</b>Clinical data of the child was collected. Blood acylcarnitine was determined with tandem mass spectrometry. DNA was extracted from the child and his parents. All exons and flanking regions of the CPT1A gene were analyzed by PCR and Sanger sequencing.</p><p><b>RESULTS</b>Analysis showed that the patient carried compound heterozygous mutations c.1787T>C and c.2201T>C of the CPT1A gene, which derived his father and mother, respectively. Both mutations were verified as novel through the retrieval of dbSNP, HGMD and 1000 genome databases. Bioinformatic analysis suggested that the mutations can affect protein function.</p><p><b>CONCLUSION</b>Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency. The c.1787T>C and c.2201T>C mutations of the CPT1A gene probably underlie the disease in this patient. Gene testing can provide important clues for genetic counseling and prenatal diagnosis.</p>


Subject(s)
Base Sequence , Carnitine O-Palmitoyltransferase , Genetics , Exons , Female , Humans , Hypoglycemia , Genetics , Infant , Lipid Metabolism, Inborn Errors , Genetics , Male , Molecular Sequence Data , Point Mutation , Pregnancy
5.
Article in Chinese | WPRIM | ID: wpr-247709

ABSTRACT

<p><b>OBJECTIVE</b>To analyze the clinical features and gene mutations in an adolescent patient affected with late-onset multiple aeyl-CoA dehydrogenase deficiency (MADD) with severe fatty liver.</p><p><b>METHODS</b>Potential mutations of the ETFDH gene were detected with polymerase chain reaction (PCR) and DNA sequencing.</p><p><b>RESULTS</b>The 13-year-and-10-month girl has presented with weakness without any other special manifestation. Laboratory tests demonstrated an elevation of myocardial enzyme levels, total cholesterol, lactic acid and abnormal serum free fatty acids. H magnetic resonance spectroscopy revealed severe fatty liver. An increase in multiple plasma acyl-carnitines was detected by gas chromatography/mass spectrometry and isobutyrylglycine in urine by screening with tandem mass spectrometry. Genetic analysis demonstrated 2 heterozygous missense mutations c.250G>A (p.Ala84Thr) and c.353G>T (p.Cys118Phe) in the ETFDH gene. The diagnosis of MADD was confirmed. The patient was given large dose of vitamin B2, which resulted in rapid clinical and biochemical improvement.</p><p><b>CONCLUSION</b>A common mutation c.250G>A and a novel mutation c.353G>T in the ETFDH gene were identified in the patient. The pathogenic role of c.353G>T (p.Cys118Phe) deserves further study. Early diagnosis of MADD and appropriate therapy is crucial for the prognosis.</p>


Subject(s)
Adolescent , Adult , Base Sequence , Electron-Transferring Flavoproteins , Genetics , Fatty Acids, Nonesterified , Blood , Fatty Liver , Blood , Genetics , Female , Humans , Infant , Iron-Sulfur Proteins , Genetics , Male , Molecular Sequence Data , Multiple Acyl Coenzyme A Dehydrogenase Deficiency , Blood , Genetics , Mutation , Oxidoreductases Acting on CH-NH Group Donors , Genetics , Pedigree
6.
Article in Chinese | WPRIM | ID: wpr-239542

ABSTRACT

<p><b>OBJECTIVE</b>To analyze PCCA and PCCB gene mutations in 10 Chinese patients with propionic acidemia(PA).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. The 39 exons and flanking sequences of the PCCA and PCCB genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>DNA sequencing has revealed that 7 patients have carried a PCCA gene mutation, 2 patients carried PCCB gene mutation and 1 patient carried mutations in both PCCA and PCCB genes. Ten PA mutations were confirmed, including 8 affecting the PCCA gene and 2 affecting the PCCB gene. Three PCCA mutations c.245G>A, IVS15+5del5, c.1288C>T and 2 PCCB mutations c.838insC, c.1087T>C were found for the first time.</p><p><b>CONCLUSION</b>Among Chinese patients with propionic acidemia patients, their genetic mutations are mainly found on the PCCA gene.</p>


Subject(s)
Child, Preschool , Female , Humans , Infant , Male , Methylmalonyl-CoA Decarboxylase , Genetics , Mutation , Propionic Acidemia , Genetics
7.
Article in Chinese | WPRIM | ID: wpr-254469

ABSTRACT

<p><b>OBJECTIVE</b>To detect potential mutations of Y9ASS1, ASL and SLC25A13 genes in four patients manifesting citrullinemia.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. Exons and their flanking sequences of the three genes were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Based on DNA sequence analysis, one case was diagnosed with argininosuccinate synthetase deficiency, and the mutation type (ASS1 gene) was c.236C>T (p.S79F) + c.431C>G (p.P144R). Two cases were diagnosed with argininosuccinic aciduria (ASL gene), and their gene mutations were c.434A>G (p.D145G) + c.1366C>T (p.R456W) and c.331C>T (p.R111W) + IVS8+2insT, respectively. A thirteen months boy who carried a heterozygous 851del4 mutation (SLC25A13 gene) was diagnosed with citrullinemia adult-onset type II.</p><p><b>CONCLUSION</b>Through analysis of relevant pathogenic genes, four patients have been diagnosed.</p>


Subject(s)
Adult , Amino Acid Sequence , Argininosuccinate Lyase , Genetics , Metabolism , Argininosuccinate Synthase , Genetics , Metabolism , Base Sequence , Citrullinemia , Genetics , Female , Humans , Infant , Male , Mitochondrial Membrane Transport Proteins , Genetics , Metabolism , Molecular Sequence Data , Pedigree , Point Mutation
8.
Article in Chinese | WPRIM | ID: wpr-291729

ABSTRACT

<p><b>OBJECTIVE</b>To identify the types of OTC gene mutations in three male patients with late onset ornithine transcarbamylase deficiency (OTCD, MIM #311250).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes. The 10 exons and their flanking sequences of the OTC gene were amplified with polymerase chain reaction and subjected to direct DNA sequencing.</p><p><b>RESULTS</b>Based on DNA sequence analysis, all of the three patients have carried OTC gene mutations. Patients 1 and 2 were both hemizygous for mutation c.586G> A(p.D196N). A novel mutation c.800G> C(p.S267T) were confirmed in patient 3.</p><p><b>CONCLUSION</b>p.S267T mutation has affected the conserved amino acid motif of the OTC protein, and is therefore a pathogenic mutation.</p>


Subject(s)
Age of Onset , Amino Acid Sequence , Base Sequence , Child , Humans , Infant , Male , Molecular Sequence Data , Mutation , Ornithine Carbamoyltransferase , Genetics , Ornithine Carbamoyltransferase Deficiency Disease , Epidemiology , Genetics , Sequence Analysis, DNA , Sequence Homology, Amino Acid
9.
Article in Chinese | WPRIM | ID: wpr-581098

ABSTRACT

Objective To observe the dynamic distribution of the extravasated Evans Blue (EB) dye points (neurogenic inflammatory response) at the skin after acute gastric mucosal injury (AGMI) and its relation to the related regular acupoints in the locations in rats. Methods A total of 70 Wistar rats were randomized into normal control (n=10),normal saline (n=10),and AGMI (n=50) groups. The AGMI group was further divided into 5 h,2 d,3 d,4 d and 5 d subgroups with 10 rats in each. AGMI model was duplicated by intragastric perfusion of diluted hydrochloric acid (HCl,0.5 mol/L). Evans Blue Dye (50 mg/kg,50 mg/mL in 0.9% saline) was given to the rats before AGMI modeling. The plasma extravasated EB points at the skin of the whole body were observed after removal of the hair. Results The extravasated EB points presented a nerve-segmental distribution,with the proportion of the points in the location being 47.5% for "Geshu" (BL 17),58.82% for "Jizhong" (GV 6),88.23% for "Pishu" (BL 20),82.35% for "Weishu" (BL 21),17.64% for "Zhongwan" (CV 12),and 5.88% for "Shangwan" (CV 13),respectively. The plasma extravasation of EB seldom appeared in normal rats and only fewer points were found in rats accepted administration of 0.9% saline. Significant differences were found between model and normal control groups,and between model and normal saline groups in the numbers of the extravasated EB points (P

10.
Chinese Journal of Neurology ; (12): 624-627, 2008.
Article in Chinese | WPRIM | ID: wpr-398551

ABSTRACT

Objective To determine whether rizatriptan has an effect on cortical spreading depression (CSD) and c-Fos expression within periaqueductal grey (PAG) induced by CSD in rats. Methods The experimental SD rats were randomly divided into group A injected with KCl, group B KCl plus rizatriptan and group C NaCL The number and amplitude of CSD were recorded after KCl or NaCl injection. C-Fos positive neurons of different layer were identified by the immunohistochemical technique 2 hours after the first injection of KCl or NaCl. Results There was no CSD in group C. The number of CSD in group A ( 10.70±3.23 ) was significantly more than that in group B (6.10±2.56, t = - 3.528, P < 0.01 ). The amplitude of CSD in group A ( 17.33 (95% CI 11.45--23.11 ) mV) was significantly greater than that in group B (11.82 (95%CI 9.24--14.70) mV, Z= -4.360, P< 0.01). There were more cFos-like immnoreactive neurons in every layer in group A than in group C (P < 0.01 ) and in group B (P < 0.05 ). Conclusion Rizatriptan has an inhibitory effect on CSD, which might induce the headache through exciting the neurons in PAG.

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