A Novel Mutation (c.200T>C) in the NAGLU Gene of a Korean Patient with Mucopolysaccharidosis IIIB

Mucopolysaccharidosis (MPS) IIIB is a lysosomal storage disorder (LSD) caused by abnormalities of the enzyme alpha-N-acetylglucosaminidase (NAGLU) that is required for degradation of heparan sulfate. The patient in this study was a 4-yr-old boy. He presented with normal height and weight, pectus carinatum, and multiple persistent Mongolian spots on his back. He had mild dysmorphic features with prominent speech developmental delays and, to a lesser extent, motor developmental delays. The cetylpyridinium chloride precipitation test revealed excessive mucopolysacchariduria (657.2 mg glycosaminoglycan/g creatinine; reference range, C (p.L67P) and c.1444C>T (p.R482W). The c.200T>C mutation was a novel finding. This is the first report of a Korean patient with MPS IIIB who was confirmed by molecular genetic analyses and biochemical investigation.

Biochemical evaluation of the protective impact of silymarin against cyclophosphamide- induced hepatotoxicity in rats

This study was designed to investigate the ameliorative effect of silymarin on the hepatotoxicity induced by cyclophosphamide [CP] in female albino rats. The results revealed that cyclophosphamide induced marked increase in relative liver weight and serum levels of ALT, AST and decrease in serum albumin level which were normalized by silymarin administration. Pretreatment with silymarin significantly attenuated cyclophosphamide-induced increases in malondialdehyde [MDA] in the liver homogenate. The results revealed that the activities of lysosomal enzymes acid phosphatase [ACP], beta-N-acetyl glucosaminidase [beta-NAG] and beta- galactosidase [beta-GAL] were increased significantly in CP-treated animals while pretreatment by silymarin caused marked attenuation in the increased activities of the three enzymes. Cyclophosphamide significantly decreased reduced glutathione [GSH], glutathione-s-transferase [GST] and glutathione reductase [GR] levels in the liver homogenate, while pretreatment with silymarin blunted the decreased levels of GSH,GST and GR. Our results revealed the potential hepatoprotective effect of silymarin against cyclophosphamide-induced hepatotoxicity. So, it may be worthy to consider the beneficial use of silymarin as supplement with cyclophosphamide therapy

Assessment of serum hyaluronic acid and N-acetylglucosamine levels in chronic hepatitis C patients

Knowledge of the stage of liver fibrosis is essential for prognosis and decisions on antiviral treatment. Liver biopsy is currently the gold standard in assessing the liver histology. There is an increasing desire for non-invasive tests to assess the stage of liver fibrosis or cirrhosis. Serum hyaluronic acid [SHA] and N-acetylglucosamine [NAG] could be a hope for clinicians to diagnose or exclude fibrosis and cirrhosis. Therefore, the present study was done to assess SHA and NAG levels in chronic hepatitis C [CHC] patients and to determine the cut off values of these markers to predict fibrosis or cirrhosis. The present study was conducted on 89 subjects [20 controls and 69 CHC patients]. The HCV infection was diagnosed based on positive HCV antibodies and positive HCV-RNA. Percutaneous-ultrasoundassisted liver biopsies were done for all patients and assessed by the METAVIR scoring system. According to the results of the liver biopsy, the patients were classified into 3 groups. Group I included 15 patients without fibrosis [F0]. Group II included 35 patients with significant fibrosis [F1-F3]. Group III included 19 patients with cirrhosis [F4]. SHA levels were determined using enzyme-linked binding protein assay Kits and NAG levels were assayed by reverse phase-high performance liquid chromatography [RP-HPLC]. There were highly significant elevations of SHA and NAG in patient group when compared to the control group. Moreover levels of SHA and NAG increase with the extent of fibrosis. SHA with cut off value of less than 25 ng/ml was used to exclude fibrosis or cirrhosis with a sensitivity of 68% and specificity of 58%. SHA with cut off value of more than 200 ng/ml was used to detect significant fibrosis with sensitivity of 93% and specificity of 95%. SHA with cut off value of more than 350 ng/ml was used to detect cirrhosis with sensitivity of 92% and specificity of 100%. NAG with cut off value of less than 25 ng/ml was used to exclude fibrosis or cirrhosis with sensitivity of 60%, specificity of 55%. NAG with cut off value of more than 40 ng/ml was used to detect significant fibrosis with sensitivity of 90% and specificity of 92%. NAG with cut off value of more than 55 ng/ml was used to detect cirrhosis with sensitivity of 90% and specificity of 86%. SHA and NAG were correlated negatively with serum albumin, prothrombin concentrations and platelet count and positively with the degree of fibrosis. Serum hyaluronic acid and N-acetylglucosamine are highly valuable and informative in detection of significant fibrosis and cirrhosis while they are of limited value in exclusion of minimal fibrosis

N-Acetyl-beta-D-glucosaminidase in acute myocardial infarction

The objective of the study was to investigate whether the lysosomal enzyme, N-Acetyl-beta-D-glucosaminidase (NAG) activity is increased in plasma of patients with acute myocardial infarction (AMI) and to determine if there is any association between plasma levels of NAG and severity of myocardial infarction (MI). NAG activity in plasma was monitored in 69 patients with AMI and 135 normal healthy subjects using a spectrofluorimetric method. A modified Aldrich ST elevation score was used to gauge the severity of MI in terms of size of the infarct. Plasma NAG levels in AMI patients and normal healthy subjects were found to be 10.92+/-7.5 U/l and 6.8+/-2.2 U/l, respectively. These two mean value when compared by Student's t-test were significantly different P = 0.0001. No statistically significant differences in NAG activity were observed in patients in terms of gender, age, location of infarct, time from onset of chest pain to blood sampling in the hospital and size of the infarct.