Find information on thousands of medical conditions and prescription drugs.

Glycogen storage disease type II

Glycogen storage disease type II (also called Pompe disease or infantile acid maltase deficiency) is a rare genetic disorder caused by a deficiency in the enzyme acid alpha-glucosidase (GAA), which is needed to break down glycogen, a stored form of sugar used for energy. It is the only glycogen storage disease with a defect in lysosomal metabolism, and was the first glycogen storage disease to be identified—in 1932. The build-up of glycogen causes progressive muscle weakness throughout the body and affects various body tissues, particularly in the heart, skeletal muscles, liver and nervous system. Transmission is by autosomal recessive inheritance. more...

Gardner's syndrome
Gastric Dumping Syndrome
Gastroesophageal reflux
Gaucher Disease
Gaucher's disease
Gelineau disease
Genu varum
Geographic tongue
Gerstmann syndrome
Gestational trophoblastic...
Giant axonal neuropathy
Giant cell arteritis
Gilbert's syndrome
Gilles de la Tourette's...
Gitelman syndrome
Glanzmann thrombasthenia
Glioblastoma multiforme
Glucose 6 phosphate...
Glycogen storage disease
Glycogen storage disease...
Glycogen storage disease...
Glycogenosis type IV
Goldenhar syndrome
Goodpasture's syndrome
Graft versus host disease
Graves' disease
Great vessels transposition
Growth hormone deficiency
Guillain-Barré syndrome

Children have a 1 in 4 chance of inheriting the disease when both parents carry the abnormal gene. It is estimated to occur in about 1 in 40,000 births.


Pompe disease has three forms defined by age of onset and progression of symptoms:

Infantile, or early onset, is noticed shortly after birth. Symptoms include severe lack of muscle tone, weakness, and enlarged liver and heart. Mental function is not affected. Development appears normal for the first weeks or months but slowly declines as the disease progresses. Swallowing may become difficult and the tongue may protrude and become enlarged. Most children die from respiratory or cardiac complications before 2 years of age.

Juvenile onset symptoms appear in early to late childhood and include progressive weakness of respiratory muscles in the trunk, diaphragm and lower limbs, as well as exercise intolerance. Intelligence is normal. Most patients do not live beyond the second or third decade of life.

Adult onset symptoms also involve generalized muscle weakness and wasting of respiratory muscles in the trunk, lower limbs, and diaphragm. Many patients report respiratory distress, headache at night or upon waking, diminished deep tendon reflexes, and proximal muscle weakness, such as difficulty in climbing stairs. Intellect is not affected. A small number of adult patients live without major symptoms or limitations


Cardiac and respiratory complications are treated symptomatically. Physical and occupational therapy may be beneficial for some patients. Alterations in diet may provide temporary improvement but will not alter the course of the disease. Genetic counseling can provide families with information regarding risk in future pregnancies.


The prognosis for individuals with Pompe disease varies according to the onset and severity of symptoms. The disease is particularly lethal in infants and young children.


[List your site here Free!]

Overview: What is insulin resistance?
From Nutrition Reviews, 3/1/00 by Kelley, David E

Insulin evokes a broad array of metabolic responses and, accordingly, can potentially be defined in myriad ways within the many metabolic pathways regulated by insulin. The most logical point of departure when defining insulin resistance is in relation to altered patterns of glucose metabolism. Even a cursory review of the pertinent literature is replete with references to insulin resistance in disorders of lipid and fatty acid metabolism, altered patterns of protein and amino acid metabolism, blunted hemodynamic responses, changes in electrolyte homeostasis, and perturbations of growth at a cellular level. Moreover, within the past decade, the term "insulin resistance syndrome" has entered the medical lexicon. Put simply, the concept of an insulin-resistant syndrome seeks to integrate many of these diverse aspects of insulin resistance into a more global concept. It has become useful for clinicians and investigators searching for an integrative approach to understanding the linkage between disorders such as type 2 diabetes, atherosclerosis, hypertension, and hyperlipidemia.

Among the first to perceive insulin resistance was Himsworth,1 based on simple and elegant studies during which the ability of insulin to blunt the rise of plasma glucose was assessed following glucose infusion. Himsworth noted very divergent responses to insulin. Among lean, young adult patients with diabetes, insulin substantially blunted the rise in glucose following glucose administration; yet in obese, older patients, insulin injections had only a marginal impact. In retrospect, it is clear that Himsworth made a fundamental observation as to the differences between type 1 diabetes, a disease of insulin deficiency, and type 2 diabetes, a disease characterized in good measure by insulin resistance. With the development of the radioimmunoassay for insulin by Yalow and others, it was soon recognized that many patients with glucose intolerance and diabetes had exaggerated, rather than deficient patterns of insulin secretion.

The development of the euglycemic insulin infusion method by Andres, DeFronzo, and colleagues2 was a major step forward because it enabled the field to move from qualitative to quantitative assessments of insulin action during in vivo human studies. The technique of the clamp entails a constant rate of insulin infusion sustained sufficiently long to attain steady-state metabolic conditions. The description "glucose clamp" refers to the process of holding the plasma glucose stable by a feedback process of repeated measurements and constant adjustment of a variable rate infusion of concentrated dextrose. As steady state metabolic conditions are achieved, generally occurring within 90-120 minutes from the onset of insulin infusions, the rate of glucose utilization is matched quantitatively by the simultaneous rate of dextrose infusion, hence the stable levels of plasma glucose. The rate of dextrose infusion is thus a quantitative measure of insulin action to stimulate glucose utilization. A number of supplemental techniques can be used to amplify the information yield of the glucose clamp.3 Indirect calorimetry can be used to estimate rates of glucose and lipid oxidation, and the dif ference from rates of glucose metabolism reflect nonoxidative glucose disposal, which, during insulin-stimulated conditions, is mostly glycogen formation. Isotopic tracers can be used to estimate rates of glucose appearance, and by accounting for concomitant glucose infusion (if any), rates of endogenous (largely hepatic) glucose production can be determined. Definitions of insulin sensitivity can be defined in terms of glucose "disposal," and further refined to pathways of glucose oxidation (and ability to suppress lipid oxidation), glucose storage, and suppression of hepatic glucose production. With the use of markers of fatty acid metabolism, insulin action in the suppression of lipolysis can be measured.

Using the paradigm of euglycemic insulin infusion as a means to measure insulin sensitivity, it was recognized that the majority of glucose disposal is to skeletal muscle. This has been delineated by extrapolation from limb balance studies, in which the arteriovenous balance of glucose was measured across a forearm or leg. Indirect calorimetry has been applied regionally to partition glucose utilization into oxidation and storage pathways across muscle or splanchnic tissues. More recently, new imaging methods have been brought to bear to aid in the study of insulin action. Nuclear magnetic resonance has been used to study the dynamic of insulin-stimulated glycogen formation.4 Among individuals with diminished rates of insulin-stimulated glucose utilization (i.e., among those with insulin resistance), large impairments in rates of glycogen formation are observed by this approach. This noninvasive approach has nicely complemented a large previous body of evidence that revealed impaired insulin activation of the glycogen synthetic pathway as the pathway of glucose metabolism that is most impaired in relation to insulin resistance.5 A current focus is to elucidate whether the key metabolic impairment occurs proximal to glycogen formation, or more specifically, whether the key impairment resides within glucose transport and phosphorylation. 6 Insulin resistance should be understood to represent most fundamentally an impairment in insulin signaling, arising from postreceptor defects in propagation of the message evoked by the binding of insulin to the receptor.7 Given the hereditary nature of type 2 diabetes and other disorders that have been linked to insulin resistance, there has been an enormous effort to discern the molecular biology of insulin resistance. Unfortunately, there does not appear to be one prevalent or even a handful of common genetic mutations that underscore insulin resistance. A current approach has been to examine the impact of genetic knockouts or overexpression within animal models of diabetes, obesity, and insulin resistance.

In keeping with the multiple potential and interactive genetic factors that predispose one to insulin resistance, there are numerous "environment" or "acquired" factors that cause or aggravate insulin resistance. Foremost among these is obesity and, in particular, central or visceral accumulation of adipose tissue.8 More "hot topics" regarding body composition related to insulin resistance are accumulation of triglyceride within skeletal muscle and altered phosopholipid composition of muscle membranes.9,10 Aging, sedentary lifestyle, high-fat diets, stress, altered androgen metabolism in men and women, increased cytokines (e.g., TNFa), patterns of skeletal muscle fiber type distribution, and a reduced capillary density within skeletal muscle are only a partial list of factors found to be associated with insulin resistance, and for many of these strong data for causality have been developed.

It is also important within these introductory remarks to outline the "insulin resistance syndrome.11,12Insulinresistant patterns of glucose metabolism are more prevalent among hypertensive compared with nonhypertensive, and among dyslipidemic compared with normolipemic individuals, to outline some of the relevant patterns. Moreover, hypertension, type 2 diabetes, and dyslipidemia tend to cluster together, often in association with upper abdominal patterns of excess fat. This "clustering" is the basis of a perception of an insulin-resistant syndrome or phenotype as playing a potentially important role in a highly prevalent illness of modern societies.

1. Himsworth Hl? Kerr RB. Insulin-sensitive and insulin-insensitive types of diabetes mellitus. Clin Sci 1939; 4:119-52

2. DeFronzo RA, Tobin JD, Andres R. Glucose clamp technique: a method for quantifying insulin secretion and resistance. Am J Physiol 1979;237(3): E214-23

3. Clinical research in diabetes and obesity. Draznin B, Rizza R, eds. Vol. I: Methods, assessment, and metabolic regulation. Totowa, New Jersey: Humana Press, 1997

4. Shulman GI, Rothman DL, Jue T, et al. Quantitation of muscle glycogen synthesis in normal subjects and subjects with non-insulin-dependent diabetes by 13C nuclear magnetic resonance spectroscopy. N Engl J Med 1990;322(4):223-8

5. Thorburn AW, Gumbiner B, Bulacan F, et al. Intracellular glucose oxidation and glycogen synthase activity are reduced in non-insulin-dependent (type II) diabetes independent of impaired glucose uptake. J Clin Invest 1990;85:522-9

6. Kelley DE, Mintun MA, Watkins SC, et al. The effect of NIDDM and obesity on glucose transport and phosphorylation in skeletal muscle. J Clin Invest 1996;97:2705-13

7. Kruszynska n Olefsky JM. Cellular and molecular mechanisms of non-insulin dependent diabetes mellitus. J Invest Med 1996;44(8):413-28

8. Goodpaster BH, Thaete FL, Simoneau J-A, Kelley DE. Subcutaneous abdominal fat and thigh muscle composition predict insulin sensitivity independently of visceral fat. Diabetes 1997;46:1579-85

9. Pan DA, Lillioja S, Kriketos AD, et al. Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes 1997;46(6):983-8

10. Goodpaster BH, Kelley DE. Role of muscle in triglyceride metabolism. Curr Opin Lipidol 1998;9:2316

11. Ferrannini E, Buzzigoli G, Bonadonna R, et al. Insulin resistance in essential hypertension. N Engl J Med 1987;317(6):350-8

12. Bonora E, Kiechl S, Willeit J, et al. Prevalence of insulin resistance in metabolic disorders: The Bruneck Study. Diabetes 1998;47:1643-9

Dr. Kelley is with the Department of Medicine, University of Pittsburgh, Pittsburgh, PA 15213, USA.

Copyright International Life Sciences Institute and Nutrition Foundation Mar 2000
Provided by ProQuest Information and Learning Company. All rights Reserved

Return to Glycogen storage disease type II
Home Contact Resources Exchange Links ebay