Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In glycogen storage disease type III (glycogen debranching enzyme (DE) deficiency), the activities of serum alanine aminotransferase, aspartate aminotransferase and lactate dehydrogenase may be strikingly elevated during childhood but are low during adult life. To determine the pattern of the elevated serum enzyme activities in relationship to diet, the biochemical subtype and clinical symptoms, 13 patients with DE deficiency were studied. Activities of serum aspartate and alanine transaminases, lactate dehydrogenase, and alkaline phosphatase were markedly elevated during infancy. Continued elevation of enzyme activities during childhood appeared to be related to DE deficiency in liver, but unrelated to DE deficiency in muscle. Activity elevations correlated inconsistently with diet and poorly with childhood growth rate or the presence of hypoglycaemia. The serum enzyme activities declined around puberty concomitantly with a decrease in liver size. Although periportal fibrosis and micronodular cirrhosis indicated the presence of hepatocellular damage during childhood, the decline in serum enzyme activities with age and the absence of overt hepatic dysfunction suggest that the fibrotic process may not always progress.
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PMID:Glycogen debranching enzyme deficiency: long-term study of serum enzyme activities and clinical features. 129 83

Laminin, hyaluronic acid (HA), procollagen III amino-terminal propeptide (PIIINP), and procollagen I carboxy-terminal propeptide (PICP) concentrations were measured by radioimmunoassay or radiometric assay in sera from 21 patients with glycogen storage disease (GSD). Laminin was increased in 16 of 29 samples from the six children with GSD I, 25/43 from the seven with GSD III, and 3/19 from the eight with GSD IX; laminin correlated with serum aspartate aminotransferase and gamma-glutamyltransferase but not with serum triglycerides, cholesterol, lactate, or urate. HA was increased in 20% of samples from GSD I, 58% from GSD III, and in none from GSD IX; HA correlated with serum lactate and urate but not with liver function tests, serum cholesterol, or triglycerides. Serum PIIINP was increased in only eight samples and PICP in only one; children with poor linear growth had low PIIINP and PICP. Immunostaining studies of nine liver biopsies taken at diagnosis showed increased laminin and PIIINP staining in portal tracts, fibrous septa, and around sinusoids in periportal regions; children with a greater degree of immunostaining did not always show significantly higher values of serum laminin or PIIINP. We speculate that raised serum laminin may reflect fibrogenesis (but not necessarily established fibrosis) in response to tissue damage in GSD, raised HA may reflect disturbed sinusoidal endothelial cell function, and low PIIINP and PICP impaired somatic growth rather than intrahepatic pathology.
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PMID:Serum concentrations of extracellular matrix components: novel markers of metabolic control and hepatic pathology in glycogen storage disease? 191 39

Glycogen storage disease type IIIa (GSD IIIa) is caused by a deficiency of the glycogen debranching enzyme (GDE), which is encoded by the Agl gene. GDE deficiency leads to the pathogenic accumulation of phosphorylase limit dextrin (PLD), an abnormal glycogen, in the liver, heart, and skeletal muscle. To further investigate the pathological mechanisms behind this disease and develop novel therapies to treat this disease, we generated a GDE-deficient mouse model by removing exons after exon 5 in the Agl gene. GDE reduction was confirmed by western blot and enzymatic activity assay. Histology revealed massive glycogen accumulation in the liver, muscle, and heart of the homozygous affected mice. Interestingly, we did not find any differences in the general appearance, growth rate, and life span between the wild-type, heterozygous, and homozygous affected mice with ad libitum feeding, except reduced motor activity after 50 weeks of age, and muscle weakness in both the forelimb and hind legs of homozygous affected mice by using the grip strength test at 62 weeks of age. However, repeated fasting resulted in decreased survival of the knockout mice. Hepatomegaly and progressive liver fibrosis were also found in the homozygous affected mice. Blood chemistry revealed that alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) activities were significantly higher in the homozygous affected mice than in both wild-type and heterozygous mice and the activity of these enzymes further increased with fasting. Creatine phosphokinase (CPK) activity was normal in young and adult homozygous affected mice. However, the activity was significantly elevated after fasting. Hypoglycemia appeared only at a young age (3 weeks) and hyperlipidemia was not observed in our model. In conclusion, with the exception of normal lipidemia, these mice recapitulate human GSD IIIa; moreover, we found that repeated fasting was detrimental to these mice. This mouse model will be useful for future investigation regarding the pathophysiology and treatment strategy of human GSD III.
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PMID:Mouse model of glycogen storage disease type III. 2461 82