Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
Atherosclerosis 1994 Sep 30
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

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

In patients with glycogen storage disease type Ia (glucose-6-phosphatase deficiency), serum triglyceride concentrations are markedly raised, whereas phospholipids and cholesterol levels are only moderately elevated. In addition, both VLDL and LDL lipoprotein fractions are raised. Despite these abnormalities, endothelial vascular dysfunction and atherosclerosis seem to be rare in such patients. In view of the crucial role of apolipoprotein E (apoE) in lipid metabolism, we studied both apoE polymorphism (40 patients) and serum concentration (20 patients) in patients with glycogen storage disease type Ia. The distribution of each allele at the apoE locus was similar to that reported in the general population, whereas serum apoE concentrations were raised in our patients. Raised apoE levels in the serum could play an important role in counterbalancing the at-risk-for-atherosclerosis lipid profile of patients with glycogen storage disease type Ia. Moreover, E3 and E4 polymorphisms, predominant in our patients, have a high triglyceride binding capacity and are thus able to increase triglyceride clearance. However, the origin of raised concentrations of apoE is not completely clear though, bearing in mind previous reports regarding serum protein concentrations in such patients, increased hepatic synthesis is likely.
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PMID:Apolipoprotein E polymorphism and serum concentrations in patients with glycogen storage disease type Ia. 1080 Oct 51

We describe 2 patients with glycogen storage disease type 1a and severe hyperlipidemia without premature atherosclerosis. Susceptibility of low-density lipoproteins to oxidation was decreased, possibly related to the ~40-fold increase in palmitate synthesis altering lipoprotein saturated fatty acid contents. These findings are potentially relevant for antihyperlipidemic treatment in patients with glycogen storage disease type 1a.
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PMID:Increased lipogenesis and resistance of lipoproteins to oxidative modification in two patients with glycogen storage disease type 1a. 1186 83

Oxidative modification of lipoproteins in vessel walls plays a key role in atherogenesis. Patients with glycogen storage disease type Ia (GSD Ia) do not develop premature atherosclerosis despite severe hyperlipidemia. We analyzed antioxidative defense and oxidative stress in plasma and serum of patients with GSD Ia (n = 17) compared to patients with type I diabetes mellitus (DMI, n = 17), familial hypercholesterolemia (FH, n = 18), and healthy controls (n = 20). We measured the total radical-trapping antioxidant parameter (TRAP), single antioxidants (sulfhydryl groups, uric acid, vitamin C, alpha-tocopherol, coenzyme Q10), malondialdehyde, oxidized low density lipoprotein (LDL) antibodies, lipid profile [cholesterol, triglyceride, lipoprotein (a)], homocysteine, and hemoglobin (Hb)A(1C). TRAP levels were elevated in the GSD Ia group (p <.01) and correlated with elevated uric acid levels (r = 0.72, p =.001). None of the other plasma antioxidants correlated with TRAP levels. DMI patients showed decreased sulfhydryl groups (p <.01) and a reduced ubiquinol-10 fraction (p <.01). Malondialdehyde (p <.001) and oxidized LDL autoantibodies (p <.05) were increased in the diabetic group. In FH patients, parameters of oxidative stress and TRAP did not differ from controls. We conclude that in GSD Ia an increased antioxidative defense in plasma may protect against lipid peroxidation and thus against premature atherosclerosis. Furthermore, we demonstrated that in DMI increased oxidative mechanisms are already present in childhood.
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PMID:Plasma antioxidants in pediatric patients with glycogen storage disease, diabetes mellitus, and hypercholesterolemia. 1208 88

With current dietary therapy, life expectancy in glycogen storage disease (GSD) has improved considerably and more children reach adulthood. Notwithstanding intensive dietary therapy, moderate to severe hyperlipidaemia is still observed frequently. There is limited information about the type and extent of hyperlipidaemia. We studied the lipid profile in 20 patients, aged 8-54 years, of the three (types I, III and IX) most common forms of adult GSD. Hyperlipidaemia was shown to be type-specific, affecting predominantly patients with GSD type Ia, who showed marked combined hypercholesterolaemia and hypertriglyceridaemia. By contrast, a heterogeneous distribution of HDL was found in patients with GSD I and III. There was no significant difference in Apo Al and Apo B concentrations between groups. In addition, mass measurements of the fractions of VLDL1, VLDL2 and IDL were raised in all patients with GSD Ia by comparison with all other patients with GSD. Patients with GSD type Ia have lipid concentrations and individual mass measurements that are consistent with ranges found in patients who have a significant risk of atherosclerosis. Accumulated evidence, however, suggest GSD type Ia patients do not have an increased risk of atherosclerotic cardiovascular disease (CVD) but the reason remains unknown. Intervention to reduce their lipid levels could therefore be on the basis of seeking to prevent the risk of pancreatitis rather than that of CVD.
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PMID:Serum lipid and lipoprotein profile of patients with glycogen storage disease types I, III and IX. 1740 2

We report a 60-year-old Japanese patient with glycogen storage disease type 1a (GSD1a) who was thoroughly evaluated for risk factors of atherosclerosis. As often observed in patients with GSD1a, this patient has multiple risk factors for atherosclerosis including hyperlipidemia, hypertension, glucose intolerance with insulin resistance, and chronic kidney disease. However, she lacked clinically evident atherosclerosis as generally observed in GSD1a patients. Unexpectedly, this patient had marked hyperadiponectinemia (27.6 microg/mL; reference range, 4.1-18.9 microg/mL) with increase in the ratio of high-molecular weight to total adiponectin. Although the reason for the hyperadiponectinemia was not clear, at least it seemed to protect against enhanced atherosclerogenesis otherwise promoted by a battery of risk factors. Although further studies are needed, hyperadiponectinemia in addition to hypoinsulinemia might explain at least in part the lack of evident atherosclerosis in patients with GSD1a.
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PMID:Lack of evident atherosclerosis despite multiple risk factors in glycogen storage disease type 1a with hyperadiponectinemia. 1788 52

The aim of this study was to investigate the endothelial dysfunction (ED) and carotid intima-media thickness (IMT) in patients with glycogen storage disease (GSD) types Ia and III. In 22 patients with GSD (13, type Ia; 9, type III) and 18 healthy subjects, endothelial functions of the brachial artery and carotid IMT were evaluated by high-resolution ultrasound. Endothelial-dependent dilatation (EDD) was assessed by establishing reactive hyperemia. EDD and carotid IMTs were compared between the three groups. Mean cholesterol level was slightly higher in GSD type III patients but the difference was not significant. Triglyceride levels and cholesterol to high density lipoprotein (HDL) ratio were significantly higher in GSD type Ia patients. EDD was significantly impaired in GSD type Ia (13% +/- 8%, P = .001) and type III (15% +/- 6%, P = .005) patients when compared with the healthy subjects (22% +/- 4%). The carotid IMT was significantly higher in both GSD type Ia (0.23 +/- 0.03 mm, P =.005) and type III (0.26 +/- 0.05 mm, P = .001) patients when compared with the healthy subjects (0.20 +/- 0.02 mm). Both GSD type Ia and type III patients show significant ED and increased IMT, which are predictors of atherosclerosis.
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PMID:Prediction of premature atherosclerosis by endothelial dysfunction and increased intima-media thickness in glycogen storage disease types Ia and III. 1790 9

Glycogen storage diseases are a group of genetic disorders involving pathways for storage of glycogen and its utilization to maintain blood glucose. Clinical manifestations include hypoglycaemia, hepatomegaly, delayed adolescence and hyperlipidaemia. Hyperlipidaemia is frequent and patients surviving long enough are thought to be at increased risk of atherosclerosis. However, no cases have previously been reported. Presented is a 27-year-old male with glycogen storage disease type 1A who sustained a pontine infarction due to basilar artery stenosis. It is believed the cause of this infarction was accelerated atherosclerosis. This is of major significance to those with this disease process who are now surviving into their third and later decades due to improved management of this condition.
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PMID:Cerebrovascular disease in type 1A glycogen storage disease. 1864 98


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