Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Individuals with type Ia glycogen storage disease (glucose-6-phosphatase deficiency) frequently develop hepatic adenomas. Potential complications involving these adenomas include malignant transformation and hemorrhage. Five of 9 patients with this disease had evidence of hepatic filling defects on radionucleotide liver scan when first evaluated at our hospital. Dietary therapy aimed at preventing hypoglycemia was begun in 7 of the 9 patients. Prevention of hypoglycemia resulted in the correction of all of the metabolic abnormalities (lactic acidosis, hyperlipidemia, hyperuricemia, and growth retardation). Treatment also corrected the marked elevation in plasma glucagon concentrations. A disappearance of the hepatic lesions occurred in 2 of the treated patients, and a marked reduction in size of the adenoma occurred in the third patient. The hepatic filling defects remained present in the two untreated patients. None of the affected patients receiving dietary therapy have developed hepatic adenomas. One of these patients is now 22 yr old and has received dietary therapy for 7 yr. Early dietary therapy seems to be effective in preventing development of adenomas as well as inducing their resolution.
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PMID:Regression of hepatic adenomas in type Ia glycogen storage disease with dietary therapy. 694 8

Four Asian babies presenting with type I glycogen storage disease during the early weeks of life are described. In one child the symptoms, metabolic acidosis, and hypoglycaemia were so easily controlled that the diagnosis was not entertained, leading to a late diagnosis. In another child the diagnosis was reached only by investigation of a fortuitously detected hyperlipidaemia. The 3 babies in whom early treatment was started are thriving, and in one, the liver histology was so normal that doubt was cast on the diagnosis initially.
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PMID:Glycogen storage disease (type I) presenting in the neonatal period. 695 21

Patients with glycogen storage disease type 1 (GSD-1) often have marked hyperlipidaemia with abnormal lipoprotein profiles. This metabolic abnormality improves, but is not fully corrected, with dietary therapy and therefore these patients may be at high risk for the development of atherosclerosis. Endothelial dysfunction is an early event in atherogenesis and can be detected in children and young adults at high risk. We studied endothelial function, using a non-invasive ultrasonographic method, in the brachial arteries of 6 adult GSD-1a patients (aged 23-33 years) with mean cholesterol of 7.9 mmol/l (range 4.7 to 14.6) and mean triglycerides of 9.1 mmol/l (range 4.1 to 21.3), and 12 age- and sex-matched normolipidaemic controls. Flow-mediated (endothelium-dependent) dilation was similar in patients and controls (8.2% vs. 10.5%; P = 0.20). Although the patient numbers are small, these results are consistent with the surprising lack of clinically evident atherosclerosis in GSD-1. The reasons these patients appear less susceptible to the damaging arterial effects of hyperlipidaemia are unknown. These results may have implications for others with secondary hyperlipidaemias.
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PMID:Hyperlipidaemia does not impair vascular endothelial function in glycogen storage disease type 1a. 785 75

The glycogen storage disorders (GSD)-I, -III, -VI and -VIII are associated with hypertriglyceridaemia or mixed hyperlipidaemia which poses the question whether these patients have an increased risk for atherosclerosis. The atherogenicity of triglycerides has remained controversial, while increased plasma cholesterol levels are generally accepted as a significant risk factor for coronary heart disease. However, clinical data show that one has to differentiate between metabolic conditions where triglycerides are atherogenic and those which are not significantly related to early onset of atherosclerosis but may cause other disorders such as pancreatitis. Among the disorders of carbohydrate metabolism patients with diabetes mellitus frequently have enhanced plasma triglycerides associated with a higher risk for coronary heart disease, while patients with certain types of glycogen storage disease have high triglyceride levels but do not seem to have an enhanced risk for atherosclerosis. Here we have compared the biochemical abnormalities and the atherogenic risk of three different disorders of glucose metabolism including GSD-I (glucose-6-phosphatase deficiency), favism (glucose-6-phosphate dehydrogenase deficiency), and diabetes mellitus which are related to either hyper- or hypolipidaemia. The available data indicate that glucose-6-phosphate (Glc-6-P) is a central molecule in cellular glucose metabolism which critically influences pentose phosphate cycle activity and, via NADPH2-generation, regulates glutathione peroxidase activity for radical detoxification and also cholesterol and triglyceride synthesis. Radical detoxification is a major protective factor for cell membrane integrity and together with an appropriate renewal of membrane lipids may protect against the development of atherosclerosis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Glucose-6-phosphate: a key compound in glycogenosis I and favism leading to hyper- or hypolipidaemia. 831 30

Two adult patients with type I glycogen storage disease (I-GSD) had chronic renal disease with heavy proteinuria. Renal biopsies showed focal glomerular sclerosis, interstitial fibrosis, tubular atrophy or vacuolation, and prominent arteriosclerosis. Marked glomerular hypertrophy was demonstrated histometrically. Oil red O staining in one patient revealed numerous lipid deposits in the glomerular mesangium, tubular epithelial cells and interstitium. Electron microscopy in the other patient revealed diffuse thickening of the glomerular basement membrane (GBM) and lipid droplets within the mesangium. The glomerular hypertrophy, thickening of the GBM, and subsequent sclerosis were similar to those in insulin-dependent diabetes mellitus. These findings may explain the similarities between the natural histories of renal involvement in the two disorders. Particularly, glomerular hypertrophy may be a key step leading to glomerular sclerosis, which is the predominant finding I-GSD. Hyperlipidemia, which is commonly seen in I-GSD, may also accelerate the glomerular sclerosing process.
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PMID:Renal histology in two adult patients with type I glycogen storage disease. 844 18

Abnormal renal diseases including nephrotic syndrome and chronic renal failure are associated with hyperlipidemia, significance of abnormal lipid metabolism has been thought to be limited in some inherited renal diseases. However, recent studies have postulated that glomerulosclerosis is induced by hyperlipidemia and is in common with atherosclerosis. This involvement is found in the progressive renal disorders, e.g., focal glomerular sclerosis, diabetic nephropathy and glycogen storage disease. Interaction between macrophages and mesangial cells may play an important role in such conditions. This evidence is supported by experimental models with hyperlipidemia. On the other hand, discovery and new hereditary metabolic disorders, such as type III hyperlipoproteinemia and lipoprotein glomerulopathy, shows that apolipoprotein (apo) E abnormalities are responsible for the glomerular lesions. Especially, lipoprotein glomerulopathy has specific features different from those of lipid-induced renal diseases. In this disease, apo E Sendai which results from new substitution (Arginine 145-->Proline) may induce intraglomerular lipoprotein thrombi characteristic of lipoprotein glomerulopathy.
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PMID:Abnormal lipid metabolism and renal disorders. 916 48

Glycogen storage disease type 1 (GSD-1), also known as von Gierke disease, is caused by a deficiency in the activity of the enzyme glucose-6-phosphatase (G6Pase). It is an autosomal recessive disorder characterized by hypoglycemia, hepatomegaly, kidney enlargement, growth retardation, lactic acidemia, hyperlipidemia and hyperuricemia. The disease presents with both clinical and biochemical heterogeneity consistent with the existence of two major subgroups, GSD-1a and GSD-1b, which have been confirmed at the molecular genetic level. GSD-1a, the most prevalent form, is caused by mutations in the G6Pase gene that abolish or greatly reduce enzymatic activity. The gene maps to chromosome 17q21 and encodes a microsomal transmembrane protein. Animal models of GSD-1a exist and are being exploited to delineate the disease more precisely. It has been proposed that GSD-1b is caused by a defect in the microsomal glucose-6-phosphate transporter. The gene responsible for GSD-1b has been mapped to chromosome 11q23 and a cDNA encoding a microsomal transmembrane protein has been identified. The function of this putative GSD-1b protein remains to be determined. These recent developments, along with newly characterized animal models of GSD-1a, are increasing our understanding of the interrelationship between the components of the G6Pase complex and type 1 glycogen storage diseases.
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PMID:Molecular Genetics of Type 1 Glycogen Storage Diseases. 1032 3

Glycogen storage disease type 1a (GSD-1a), characterized by hypoglycemia, liver and kidney enlargement, growth retardation, hyperlipidemia, and hyperuricemia, is caused by a deficiency in glucose-6-phosphatase (G6Pase), a key enzyme in glucose homeostasis. To evaluate the feasibility of gene replacement therapy for GSD-1a, we have infused adenoviral vector containing the murine G6Pase gene (Ad-mG6Pase) into G6Pase-deficient (G6Pase(-/-)) mice that manifest symptoms characteristic of human GSD-1a. Whereas <15% of G6Pase(-/-) mice under glucose therapy survived weaning, a 100% survival rate was achieved when G6Pase(-/-) mice were infused with Ad-mG6Pase, 90% of which lived to 3 months of age. Hepatic G6Pase activity in Ad-mG6Pase-infused mice was restored to 19% of that in G6Pase(+/+) mice at 7-14 days post-infusion; the activity persisted for at least 70 days. Ad-mG6Pase infusion also greatly improved growth of G6Pase(-/-) mice and normalized plasma glucose, cholesterol, triglyceride, and uric acid profiles. Furthermore, liver and kidney enlargement was less pronounced with near-normal levels of glycogen depositions in both organs. Our data demonstrate that a single administration of a recombinant adenoviral vector can alleviate the pathological manifestations of GSD-1a in mice, suggesting that this disorder in humans can potentially be corrected by gene therapy.
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PMID:Correction of glycogen storage disease type 1a in a mouse model by gene therapy. 1062 14

The clinical manifestations of type 1 glycogen storage disease (GSD-1) in patients deficient in the glucose-6-phosphatase (G6Pase) system (e.g. growth retardation, hepatomegaly, hyperlipidemia, and renal dysfunction) are shared by Hnf1alpha(-/-) mice deficient of a transcriptional activator, hepatocyte nuclear factor 1alpha (HNF1alpha). However, the molecular mechanism is unknown. The G6Pase system, essential for the maintenance of glucose homeostasis, is comprised of glucose 6-phosphate transporter (G6PT) and G6Pase. G6PT translocates G6P from the cytoplasm to the lumen of the endoplasmic reticulum where it is metabolized by G6Pase to glucose and phosphate. Deficiencies in G6Pase and G6PT cause GSD-1a and GSD-1b, respectively. Hnf1alpha(-/-) mice also develop noninsulin-dependent diabetes mellitus caused by defective insulin secretion. In this study, we sought to determine whether there is a molecular link between HNF1alpha deficiency and function of the G6Pase system. Transactivation studies revealed that HNF1alpha is required for transcription of the G6PT gene. Hepatic G6PT mRNA levels and microsomal G6P transport activity are also markedly reduced in Hnf1alpha(-/-) mice as compared with Hnf1alpha(+/+) and Hnf1alpha(+/-) littermates. On the other hand, hepatic G6Pase mRNA expression and activity are up-regulated in Hnf1alpha(-/-) mice, consistent with observations that G6Pase expression is increased in diabetic animals. Taken together, the results strongly suggest that metabolic abnormalities in HNF1alpha-null mice are caused in part by G6PT deficiency and by perturbations of the G6Pase system.
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PMID:A molecular link between the common phenotypes of type 1 glycogen storage disease and HNF1alpha-null mice. 1112 25

Mutations in the glucose-6-phosphatase (G6Pase) gene are responsible for glycogen storage disease type Ia (GSDIa). This disease is characterized by growth retardation, hepatomegaly, hypoglycemia, hyperlipidemia, and lactic acidosis. In this study, we report mutations in the G6Pase gene in 8 of 25 Brazilian patients with clinical symptoms of GSDIa. Five previously described mutations (R83C, Q347X, V338F, D38V, and G68R) were detected. The two most common mutations identified were R83C and Q347X, accounting for 8 of 14 (57.14%) mutant alleles. A 1,176 single-nucleotide polymorphism and two intronic mutations (IVS3-58T>A and IVS4+10G>A) were also analyzed. We used the minigene strategy in order to verify the effect of these intronic mutations on the splicing mechanism. This study emphasizes that molecular genetic analysis is a reliable and convenient alternative to the assay of enzyme activity in a fresh liver biopsy specimen for diagnosing GSDIa.
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PMID:Glycogen storage disease type Ia: molecular study in Brazilian patients. 1131 May 82


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