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)

In this retrospective study from five centres, 139 patients over 10 years of age with glycogen storage disease types I, III, VI and IX are described. Almost half of the patients with glycogen storage disease type Ia had retarded growth and most had hyperlipidaemia. One-third of the patients had adenomas, although none of these showed malignant transformations. With increasing age the growth, liver size and hyperlipidaemia of patients with glycogen storage disease type III improve. However, there was a high incidence of myopathy and cardiomyopathy. Patients with glycogen storage disease types VI and IX had a normal growth pattern after childhood. Hepatomegaly and hypercholesterolaemia, however, were still present in half of the patients.
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PMID:The long-term outcome of patients with glycogen storage diseases. 212 9

The introduction of continuous nocturnal enteral glucose feeds and uncooked cornstarch has improved the prognosis for patients with the hepatic glycogen storage diseases. An increasing number of patients are surviving into adulthood in better health, but still at some medical cost. In this review we examine bone mineralization, renal function, hepatic tumours, and vascular endothelial function in GSD I and cardiac function in GSD III. All females over the age of 5 years with GSD I, III, VI and IX had morphologically polycystic ovaries. Thirteen adult GSD I patients have been studied, and been found to have poor bone mineralization and marked renal glomerular and tubular dysfunction. More than half of these patients also had focal hepatic lesions on sonography and yet vascular endothelial function was preserved in the face of hyperlipidaemia. In 12 GSD III patients, one had a focal hepatic lesion and 6 had pronounced left ventricular hypertrophy, although cardiorespiratory function was normal. These data emphasize the multisystem nature of these disorders and highlight the need for careful longterm follow-up.
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PMID:The hepatic glycogen storage diseases--problems beyond childhood. 749 4

Deficiency of amylo-1,6-glucosidase, 4-alpha-glucanotransferase enzyme (AGL or glycogen debrancher enzyme) is responsible for glycogen storage disease type III, a rare autosomal recessive disorder of glycogen metabolism. The AGL gene is located on chromosome 1p21, and contains 35 exons translated in a monomeric protein product. The disease has recognized clinical and biochemical heterogeneity, reflecting the genotype-phenotype heterogeneity among different subjects. The clinical manifestations of GSD III are represented by hepatomegaly, hypoglycemia, hyperlipidemia, short stature and, in a number of subjects, cardiomyopathy and myopathy. In this article, we discuss the genotypic-phenotypic heterogeneity of GSD III by the molecular characterization of mutations responsible for the disease on a collection of 18 independent alleles from the Mediterranean area. We identified by heteroduplex band shift, DNA direct sequencing, and restriction analysis, seven novel mutations (four nonsense point-mutations: R34X, S530X, R1218X, W1398X; two microinsertions: 1072insT and 4724insAA; and one bp deletion: 676DeltaG), together with two new cases carrying a IVS21 + 1 G --> A splicing site mutation previously described in Italian patients. Altogether, 15 alleles were characterized. The correlation between type of mutation and clinical severity was studied in six patients in whom both mutated alleles were detected. Our data confirm the extreme genetic heterogeneity of this disease, thus precluding a strategy of mutation finding based on screening of recurrent common mutations.
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PMID:Clinical and genetic variability of glycogen storage disease type IIIa: seven novel AGL gene mutations in the Mediterranean area. 1197 76

FM-VP4 is a phytosterol analog under development by Forbes Medi-Tech for the potential treatment of hyperlipidemia and hypercholesterolemia. By March 2002, FM-VP4 had entered phase I clinical trials and phase II trials were underway by late 2002.
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PMID:FM-VP4 Forbes Medi-Tech. 1458 58

Glycogenosis type III (Cori disease) is an autosomal recessive disorder caused by the deficiency of the glycogen debranching enzyme, encoded by the AGL gene, and existing in six isoforms alternately spliced in a tissue-specific way. Generally, disease onset occurs early on starting from the first year of life, with hepatomegaly, hypoglycemia, hyperlipidemia, increased CK levels, and, in some cases, short stature and slight mental retardation. Frequently, hepatomegaly tends to resolve spontaneously and inexplicably during childhood, when myopathy, often associated with cardiomyopathy, arises. This disease is known to lack almost invariably clear links between the genotype and clinical phenotype. We describe nine new mutations in Italian patients: four nonsense (p.Arg285X, p.Lys422X, p.Arg910X, p.Arg977X), three frameshift (c.442delA, c.753_756delGACA, c.3963delG), and two missense (p.Ala1120Pro, p.Arg524His). Particularly, the nonsense p.Arg285X is linked to an exonic splicing enhancer and it was found to produce two species of transcripts at the same time. Moreover, we discuss a subgroup of subjects carrying c.2681+1G>A, which has proven to be the most frequent mutation among our patients. The previously described c.664+3A>G was also detected in two patients, both homozygous. The present work is yet another confirmation that the individual genetic background plays a pivotal role in influencing the phenotypes, as occurs in other metabolic diseases.
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PMID:Hepatic and neuromuscular forms of glycogenosis type III: nine mutations in AGL. 1670 13

There are 3 cases of liver type glycogen storage diseases. All of them presented with protruding abdomen, failure to thrive, doll face and mark hepatomegaly. Laboratory findings were hypoglycemia, metabolic acidosis, abnormal liver function test, hyperlipidemia and prolonged bleeding time in GSD Ia. GSD III has no hypoglycemia and borderline hyperuricemia. Glucagon stimulation test helps to differentiate typing. The aim of treatment is to prevent hypoglycemia, suppress lactic acid production, decrease blood lipid and uric acid levels and enhances statural growth by uncooked cornstarch. Complications such as epistaxis and suspected liver adenoma have to be closely followed up. Genetic counseling for both types GSD are autosomal recessive with recurrence risk of 25%. Prenatal diagnosis by enzymes assay or molecular diagnosi are not available in this hospital.
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PMID:Glycogen storage diseases in Thai patients: Phramongkutklao Hospital experience. 1685 72

Glycogen storage disease type III (GSD III) is a very rare disorder caused by a deficiency in the activities of glycogen debranching enzymes (amylo-1-6-glucosidase and 4-alpha-glucanotransferase). GSD III is characterized by the accumulation of abnormal glycogen in the liver and skeletal muscle. The primary clinical manifestations are hepatomegaly, fasting hypoglycemia, and hyperlipidemia in infants. We report a rare case of GSD III in an adult. A 52-year-old woman presented to our clinic due to dyspnea on exertion, severe general weakness, and hepatomegaly. Hypertrophic cardiomyopathy was diagnosed based on echocardiogram findings. The microscopic findings of liver and skeletal muscle biopsies were consistent with the diagnosis of GSD. DNA analysis prompted by clinical and pathologic findings led to a definitive diagnosis of GSD IIIa. Diet therapy with cornstarch was started, and the patient was followed closely. This represents the first reported case of GSD IIIa diagnosed in an adult in Korea.
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PMID:An adult case of glycogen storage disease type IIIa. 1861 70

While the presence of hyperlipidaemia in glycogen storage disease (GSD) type Ia and Ib is generally accepted, few investigators have adequately assessed lipid profiles of GSD III in children, in whom the presence of hyperlipidaemia may be most prominent. We analysed the lipid profiles in 44 GSD III patients from 6 months to 30 years of age. Hypertriglyceridaemia and hypercholesterolaemia were common in children younger than 3 years of age. Hypertriglyceridaemia correlated negatively with age, and may reflect increased severity of hypoglycaemia in this younger population. The presence of hyperlipidaemia during childhood in these patients identifies another GSD population that could be at risk for early cardiovascular disease (CVD). Consequently, the outcome of clinical trials investigating the vascular effect of hyperlipidaemia in GSD applies to types other than GSD I.
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PMID:Hyperlipidemia in glycogen storage disease type III: effect of age and metabolic control. 1870 45

Glycogen Storage Disease type III (GSD III) is an autosomal recessive disorder in which a mutation in the AGL gene causes deficiency of the glycogen debranching enzyme. In childhood, it is characterized by hepatomegaly, keto-hypoglycemic episodes after short periods of fasting, and hyperlipidemia. In adulthood, myopathy, cardiomyopathy, and liver cirrhosis are the main complications. To determine the genotype of the GSD III patients (n = 14) diagnosed and treated in our center, mutation analysis was performed by either denaturing gradient gel electrophoresis or full gene sequencing. We developed, validated and applied both methods, and in all patients a mutation was identified on both alleles. Five novel pathogenic mutations were identified in seven patients, including four missense mutations (c.643G>A, p.Asp215Asn; c.655A>G, p.Asn219Asp; c.1027C>T, p.Arg343Trp; c.1877A>G, p.His626Arg) and one frameshift mutation (c.3911delA, p.Asn1304fs). The c.643G>A, p.Asp215Asn mutation is related with type IIIa, as this mutation was found homozygously in two type IIIa patients. In addition to five novel mutations, we present new genotype-phenotype relationships for c.2039G>A, p.Trp680X; c.753_756delCAGA, p.Asp251fs; and the intron 32 c.4260-12A>G splice site mutation. The p.Trp680X mutation was found homozygously in four patients, presenting a mild IIIa phenotype with mild skeletal myopathy, elevated CK values, and no cardiomyopathy. The p.Asp251fs mutation was found homozygously in one patient presenting with a severe IIIa phenotype, with skeletal myopathy, and severe symptomatic cardiomyopathy. The c.4260-12A>G mutation was found heterozygously, together with the p.Arg343Trp mutation in a severe IIIb patient who developed liver cirrhosis and hepatocellular carcinoma, necessitating an orthotopic liver transplantation.
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PMID:Mutation Analysis in Glycogen Storage Disease Type III Patients in the Netherlands: Novel Genotype-Phenotype Relationships and Five Novel Mutations in the AGL Gene. 2343 Apr 90

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


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