Glycogen storage disease type I or von Gierke's disease, is the most common of the glycogen storage diseases. This genetic disease results from deficiency of the enzyme glucose-6-phosphatase. This deficiency impairs the ability of the liver to produce free glucose from glycogen and from gluconeogenesis. Since these are the two principal metabolic mechanisms by which the liver supplies glucose to the rest of the body during periods of fasting, it causes severe hypoglycemia. Reduced glycogen breakdown results in increased glycogen storage in liver and kidneys, causing enlargement of both. Both organs function normally in childhood but are susceptible to a variety of problems in the adult years. Other metabolic derangements include lactic acidosis and hyperlipidemia. Frequent or continuous feedings of cornstarch or other carbohydrates are the principal treatment. Other therapeutic measures may be needed for associated problems. MedlinePlus (medlineplus. ... eMedicine is an online clinical medical knowledge base that was founded in 1996. ... The Diseases Database is a free website that provides information about the relationships between medical conditions, symptoms, and medications. ... Glycogen storage disease is any one of several inborn errors of metabolism that result from enzyme defects that affect the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. ... A genetic disorder, or genetic disease is a disease caused, at least in part, by the genes of the person with the disease. ... Ribbon diagram of the catalytically perfect enzyme TIM. An enzyme is a protein that catalyzes, or speeds up, a chemical reaction. ... Glucose 6-phosphatase is an enzyme in the glycogenolysis pathway that removes the phosphate from glucose 6-phosphate. ... The liver is one of the largest internal organs of the human body. ... Glucose (Glc), a monosaccharide, is one of the most important carbohydrates. ... Electron micrograph of a section of a liver cell showing glycogen deposits as accumulations of electron dense particles (arrows). ... Gluconeogenesis, ultimately, is the generation of glucose from noncarbohydrate sources like lactate, glycerol, and amino acids. ... Santorio Santorio (1561-1636) in his steelyard balance, from Ars de statica medecina, first published 1614 Metabolism (from μεταβολισμος (metabolismos)), the Greek word for change, or overthrow (Etymonline)), is the biochemical modification of chemical compounds in living organisms and cells. ... Hypoglycemia is a medical term referring to a pathologic state produced by a lower than normal amount of sugar (glucose) in the blood. ... Lactic acidosis is a condition caused by the buildup of lactic acid in the body. ... Hypercholesterolemia (literally: high blood cholesterol) is the presence of high levels of cholesterol in the blood. ... Products made out of cornstarch Cornstarch, or cornflour, is the starch of the maize grain, commonly known as corn. ... Carbohydrates are chemical compounds that contain oxygen, hydrogen, and carbon atoms. ...

Types of GSD I and molecular biology

Glucose-6-phosphatase is an enzyme located on the inner membrane of the endoplasmic reticulum. The catalytic unit is associated with a calcium binding protein, and three transport proteins (T1, T2, T3) that facilitate movement of glucose-6-phosphate (G6P), phosphate, and glucose (respectively) into and out of the enzyme. It has been suggested that Net flux be merged into this article or section. ... The endoplasmic reticulum or ER (endoplasmic means within the cytoplasm, reticulum means little net) is an organelle found in all eukaryotic cells. ... Generic graph showing the effect of a catalyst in an hypotetical exothermic chemical reaction. ... General Name, Symbol, Number calcium, Ca, 20 Chemical series alkaline earth metals Group, Period, Block 2, 4, s Appearance silvery white Atomic mass 40. ... A representation of the 3D structure of myoglobin, showing coloured alpha helices. ... In chemistry, a phosphate is a polyatomic ion or radical consisting of one phosphorus atom and four oxygen. ... Glucose (Glc), a monosaccharide, is one of the most important carbohydrates. ...

The most common forms of GSD I are designated GSD Ia and GSD Ib, the former accounting for over 80% of diagnosed cases and the latter for less than 20%. A few rarer forms have been described. GSD Ia results from mutations of G6PC, the gene for glucose-6-phosphatase. G6PC is located on chromosome 17q21. GSD Ib results from mutations of the gene for T1, the G6P transporter. The metabolic characteristics of GSD Ia and Ib are quite similar, but Ib incurs a few additional problems (described below). This stylistic schematic diagram shows a gene in relation to the double helix structure of DNA and to a chromosome (right). ... Figure 1: Chromosome. ...

Genetics, inheritance, and incidence

Like most serious enzyme deficiencies, GSD Ia is inherited as an autosomal recessive disease. Heterozygote carriers (parents) are asymptomatic. As for other autosomal recessive diseases, the recurrence risk for each subsequent child of the same parents is 25%. Prenatal diagnosis has been made by fetal liver biopsy at 18-22 weeks of gestation, but no fetal treatment has been proposed. Prenatal diagnosis is possible with fetal DNA obtained by chorionic villus sampling when a fetus is known to be at risk. In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Heterozygote cells are diploid or polyploid and have different alleles at a locus (position) on homologous chromosomes. ... In genetics, the term recessive gene refers to an allele that causes a phenotype (visible or detectable characteristic) that is only seen in a homozygous genotype (an organism that has two copies of the same allele). ... Prenatal diagnosis is the diagnosis of disease or condition in a fetus or embryo before it is born. ... A biopsy (in Greek: bios = life and opsy = look/appearance) is a medical test involving the removal of cells or tissues for examination. ... Space-filling model of a section of DNA molecule Deoxyribonucleic acid (DNA) is a nucleic acid that contains the genetic instructions specifying the biological development of all cellular forms of life (and most viruses). ... Chorionic villus sampling (CVS) is a form of prenatal diagnosis to determine genetic abnormalities in the fetus. ...

GSD Ia has an incidence in the American population of approximately 1 in 100,000 to 200,000 births. None of the glycogenoses are currently detected by standard or extended newborn screening. In optics one considers angles of incidence. ... Newborn screening is the process of testing newborn babies for treatable genetic, endocrinologic, metabolic and hematologic diseases. ...

Metabolic pathophysiology

Normal carbohydrate balance and maintenance of blood glucose levels

Glycogen in liver and (to a lesser degree) kidneys serves as a form of stored, rapidly accessible glucose, so that the blood glucose level can be maintained between meals. For about 3 hours after a carbohydrate-containing meal, high insulin levels direct liver cells to take glucose from the blood, to convert it to glucose-6-phosphate (G6P), and to add the G6P molecules to the ends of chains of glycogen (glycogen synthesis). Excess G6P is also shunted into production of triglycerides and exported for storage in adipose tissue as fat. Triglycerides (also known as triacylglycerols or triacylglycerides) are glycerides in which the glycerol is esterified with three fatty acids. ... Adipose tissue is an anatomical term for loose connective tissue composed of adipocytes. ... Fat is one of the three main classes of food and, at approximately 38 kJ (9 kilocalories) per gram, as compared to sugar with 17 kJ (4 kcal) per gram or ethanol with 29 kJ (7 kcal) per gram, is most concentrated form of metabolic energy available to humans. ...

When digestion of a meal is complete, insulin levels fall, and enzyme systems in the liver cells begin to remove glucose molecules from strands of glycogen in the form of G6P. This process is termed glycogenolysis. The G6P remains within the liver cell unless the phosphate is cleaved by glucose-6-phosphatase. This dephosphorylation reaction produces free glucose and free PO₄ anions. The free glucose molecules can be transported out of the liver cells into the blood to maintain an adequate supply of glucose to the brain and other organs of the body. Glycogenolysis can supply the glucose needs of an adult body for 12-18 hours. Digestion is the process whereby a biological entity processes a substance, in order to chemically convert the substance into nutrients. ... Glycogenolysis is the catabolism of glycogen (requiring removal of glucose unit from glycogen and addition of phosphate) thus producing glucose 1-phosphate, and subsequently reconfigured (C-1 -> C-6) to yield glucose 6-phosphate, a potent reaction intermediary leading to glucose available to the blood and brain, pyruvic acid (yet... The process of removing phosphate groups from an organic compound (as ATP) by hydrolysis ... An anion is an ion with negative charge. ... Comparative brain sizes In animals, the brain, or encephalon (Greek for in the head), acts as the control center of the central nervous system. ...

When fasting continues for more than a few hours, falling insulin levels permit catabolism of muscle protein and triglycerides from adipose tissue. The products of these processes are amino acids (mainly alanine), free fatty acids, and lactic acid. Free fatty acids from triglycerides are converted to ketones, and to acetyl-CoA. Alanine, lactic acid, and acetyl-CoA are used to synthesize new G6P in liver cells by the process of gluconeogenesis. The last step of normal gluconeogenesis, like the last step of glycogenolysis, is the dephosphorylation of G6P by glucose-6-phosphatase to free glucose and PO₄. Anabolism is the aspect of metabolism that contributes to growth. ... A top-down view of skeletal muscle Muscle is a contractile form of tissue. ... In chemistry, an amino acid is any molecule that contains both amino and carboxylic acid functional groups. ... Alanine is one of the 20 most common natural amino acids. ... In chemistry, especially biochemistry, a fatty acid is a carboxylic acid (or organic acid), often with a long aliphatic tail (long chains), either saturated or unsaturated. ... Structural formula of lactic acid Lactic acid (α-hydroxypropionic acid, AHA),also known as milk acid, is a chemical compound that plays a role in several biochemical processes. ... A ketone is either the functional group characterized by a carbonyl group linked to two other carbon atoms or a compound that contains this functional group. ... Categories: Biochemistry stubs | Thiols ... Gluconeogenesis, ultimately, is the generation of glucose from noncarbohydrate sources like lactate, glycerol, and amino acids. ...

Thus glucose-6-phosphatase mediates the final, key, step in both of the two main processes of glucose production during fasting. In fact the effect is amplified because the resulting high levels of glucose-6-phosphate inhibit earlier key steps in both glycogenolysis and gluconeogenesis.

Pathophysiology of the metabolic effects of glucose-6-phosphatase deficiency

The principal metabolic effects of deficiency of glucose-6-phosphatase are:

• hypoglycemia
• lactic acidosis
• hypertriglyceridemia
• hyperuricemia

The hypoglycemia of GSD I is termed "fasting", or "post-absorptive", meaning that it occurs after completion of digestion of a meal-- usually about 4 hours later. This inability to maintain adequate blood glucose levels during fasting resuls from the combined impairment of both glycogenolysis and gluconeogenesis. Fasting hypoglycemia is often the most significant problem in GSD I, and typically the problem that leads to the diagnosis. Chronic hypoglycemia produces secondary metabolic adaptations, including chronically low insulin levels and high levels of glucagon and cortisol. Hypoglycemia is a medical term referring to a pathologic state produced by a lower than normal amount of sugar (glucose) in the blood. ... Lactic acidosis is a condition caused by the buildup of lactic acid in the body. ... In medicine, hypertriglyceridemia denotes high (hyper-) blood levels (-emia) of triglycerides, the most abundant fatty molecule in most organisms. ... Hyperuricemia is the presence of high levels of uric acid in the blood. ... The structure of insulin Red: carbon; green: oxygen; blue: nitrogen; pink: sulfur. ... Glucagon ball and stick model Glucagon is a 29 amino acid polypeptide acting as an important hormone in carbohydrate metabolism. ... Cortisol is a corticosteroid hormone that is involved in the response to stress; it increases blood pressure and blood sugar levels and suppresses the immune system. ...

Lactic acidosis arises from impairment of gluconeogenesis. Lactic acid is generated both in the liver and muscle and is oxidized by NAD⁺ to pyruvic acid and then converted via the gluconeogenenic pathway to G6P. Accumulation of G6P inhibits conversion of lactate to pyruvate. The lactic acid level rises during fasting as glucose falls. In people with GSD I, it may not fall entirely to normal even when normal glucose levels are restored. Pyruvic acid (CH3COCO2H) is an alpha-keto acid, of the keto acid group. ...

Hypertriglyceridemia resulting from amplified triglyceride production is another indirect effect of impaired gluconeogenesis, amplified by chronically low insulin levels. During fasting, the normal conversion of triglycerides to free fatty acids, ketones, and ultimately glucose is impaired. Triglyceride levels in GSD I can reach several times normal and serve as a clinical index of "metabolic control".

Hyperuricemia results from a combination of increased generation and decreased excretiion of uric acid, which is generated when increased amounts of G6P are metabolized via the pentose phosphate pathway. It is also a byproduct of purine degradation. Uric acid competes with lactic acid and other organic acids for renal excretion in the urine. In GSD I increased availability of G6P for the pentose phosphate pathway, increased rates of catabolism, and diminished urinary excretion due to high levels of lactic acid all combine to produce uric acid levels several times normal. Although hyperuricemia is asymptomatic for years, kidney and joint damage gradually accrue. Uric acid is an organic compound of carbon, nitrogen, oxygen and hydrogen and the structure shown right: Uric acid is the final oxidation product of purine metabolism in the human body and is found in small amounts in urine. ... The pentose phosphate pathway (also called Phosphogluconate Pathway, or Hexose Monophosphate Shunt) is a process that serves to generate NADPH and the synthesis of pentose (5-carbon) sugars. ... Purine is a heterocyclic aromatic organic compound, consisting of a pyrimidine ring fused to an imidazole ring. ...

Principal clinical problems

Clinical manifestations result, directly or indirectly, from

1. inability to maintain an adequate blood glucose level during the post-absorptive hours of each day;
2. organ changes due to glycogen accumulation;
3. excessive lactic acid generation;
4. damage to tissue from hyperuricemia;
5. in GSD Ib, bleeding and infection risk from blood cell effects.

Hypoglycemia

Hypoglycemia is the central clinical problem, the one that is most damaging, and the one that most often prompts the initial diagnosis. Maternal glucose transferred across the placenta prevents hypoglycemia in a fetus with GSD I, but the liver is enlarged with glycogen at birth. The inability to generate and release glucose soon results in hypoglycemia, and occasionally in lactic acidosis fulminant enough to appear as a primary respiratory problem in the newborn period. Neurological manifestations are less severe than if the hypoglycemia were more acute. The brain's habituation to mild hypoglycemia is at least partly explained by use of alternative fuels, primarily lactate. Hypoglycemia is a medical term referring to a pathologic state produced by a lower than normal amount of sugar (glucose) in the blood. ... The placenta is an ephemeral (temporary) organ present only in female placental mammals during gestation (pregnancy). ...

More commonly, infants with GSD I tolerate without obvious symptoms a chronic, mild hypoglycemia and compensated lactic acidosis between feedings. Blood glucose levels are typically 25 to 50 mg/dl (1.4-2.8 mM). These infants continue to need oral carbohydrates every few hours. Many never sleep through the night even in the second year of life. They may be pale, clammy, and irritable a few hours after a meal. Developmental delay is not an intrinsic or inevitable effect of glucose-6-phosphatase deficiency but is common if the diagnosis is not made in early infancy. Mental retardation (abbreviated as MR), is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal intellectual capacity as an adult. ...

Although mild hypoglycemia for much of the day may go unsuspected, the metabolic adaptations described above make severe hypoglycemic episodes, with unconsciousness or seizure, uncommon before treatment. Episodes which occur are likely to happen in the morning before breakfast. GSD I is therefore a potential cause of ketotic hypoglycemia in young children. Ketotic hypoglycemia is a medical term used in two ways: (1) broadly, to refer to any circumstance in which low blood glucose is accompanied by ketosis, and (2) in a much more restrictive way to refer to recurrent episodes of hypoglycemic symptoms with ketosis and, often, vomiting, in young children. ...

Once the diagnosis has been made, the principal goal of treatment is to maintain an adequate glucose level and prevent hypoglycemia.

Hepatomegaly and liver problems

Impairment of glycogenolysis also causes the characteristic enlargement of the liver due to accumulation of glycogen. Glycogen also accumulates in kidneys and small intestine. Hepatomegaly, usually without splenomegaly, begins to develop in fetal life and is usually noticeable in the first few months of life. By the time the child is standing and walking, the hepatomegaly may be severe enough to cause the abdomen to protrude. The liver edge is often at or below the level of the umbilicus. Other liver functions are usually spared, and liver enzymes and bilirubin are usually normal. Hepatomegaly is an enlargement of the liver (swelling). ... An umbilicus which appears as a depression in the abdomen is referred to as an innie. The umbilicus (commonly called a navel, or belly or tummy button), is essentially a scar caused at birth by the removal of the umbilical cord from a newborn baby. ... Liver function tests (LFTs or LFs), are groups of clinical biochemistry laboratory blood assays designed to give a doctor or other health professional information about the state of a patients liver. ... Bilirubin is a yellow breakdown product of haem (heme in American English). ...

However, there is a risk of developing tumors of the liver by adolescence or adult ages, and periodic ultrasound examinations of the liver are recommended from late childhood onward. Occasional cases of various types of liver disease and failure have been reported in children and adults with GSD I.

Lactic acidosis

Impaired gluconeogenesis results in elevations of lactic acid (4-10 mM) even when the child is well. In an episode of metabolic decompensation, lactic acid levels abruptly rise and can exceed 15 mM, producing severe metabolic acidosis. Uric acid, ketoacids, and free fatty acids further increase the anion gap. Manifestations of severe metabolic acidosis include vomiting and hyperpnea, which can exacerbate hypoglycemia by reducing oral intake. Repeated episodes of vomiting with hypoglycemia and dehydration may occur in infancy and childhood, precipitated by (or mimicking) infections such as gastroenteritis or pneumonia. In medicine, hyperventilation, also known as tachypnea or hyperpnea, is the state of breathing faster or deeper than necessary, and thereby reducing the carbon dioxide concentration of the blood below normal. ... Vomiting (or emesis) is the forceful expulsion of the contents of ones stomach through the mouth. ... Dehydration is the removal of water (hydor in ancient Greek) from an object. ... An infection is the detrimental colonization of a host organism by a foreign species. ... Gastroenteritis, or inflammation of the gastrointestinal tract, is an illness of fever, diarrhoea and/or vomiting caused by an infectious virus, bacterium or parasite. ... Pneumonia is an illness of the lungs and respiratory system in which the microscopic, air-filled sacs (alveoli) responsible for absorbing oxygen from the atmosphere become inflamed and flooded with fluid. ...

Growth failure

Without treatment, growth failure is common, due to chronically low insulin levels, persistent acidosis, chronic elevation of catabolic hormones, calorie insufficiency, and/or malabsorption. Growth failure is a medical term for a pattern of a childs growth which is poorer than normal for age, sex, stage of maturation, and genetic height expectation. ... A calorie is a unit of measurement for energy. ... Malabsorption is the state of impaired absorption of nutrients in the small intestine. ...

Hyperlipidemia and blood vessel effects

A secondary effect of low insulin levels is hypertriglyceridemia. Triglycerides in the 400–800 mg/dl range may produce visible lipemia, and even a mild pseudohyponatremia due to a reduced aqueous fraction of the serum. Cholesterol is only mildly elevated. Blood plasma is a component of blood. ... Cholesterol chemical structure Cholesterol is a steroid, a lipid, and an alcohol, found in the cell membranes of all body tissues, and transported in the blood plasma of all animals. ...

Hyperuricemia and joint problems

A further effect of chronic lactic acidosis in GSD I is hyperuricemia, as lactic acid and uric acid compete for the same renal tubular transport mechanism. Increased purine catabolism is an additional contributing factor. Uric acid levels of 6-12 mg/dl are typical of GSD I. Allopurinol may be needed to prevent uric acid nephropathy and gout.

Kidney effects

Kidneys are usually 10 to 20% enlarged with stored glycogen. This does not usually cause clinical problems in childhood, with the occasional exception of a Fanconi syndrome with multiple derangements of renal tubular reabsorption, including proximal renal tubular acidosis with bicarbonate and phosphate wasting. However, prolonged hyperuricemia can cause uric acid nephropathy. In adults with GSD I, chronic glomerular damage similar to diabetic nephropathy may lead to renal failure.

Bowel effects

Intestinal involvement can cause mild malabsorption with sloppy stools but usually requires no treatment. Malabsorption is the state of impaired absorption of nutrients in the small intestine. ...

Infection risk

Blood clotting problems

Impaired platelet aggregation is an uncommon effect of chronic hypoglycemia. It may cause clinically significant bleeding, especially epistaxis.

Neurodevelopmental effects

Developmental delay is a potential secondary effect of chronic or recurrent hypoglycemia, but is at least theoretically preventable. Because normal brain and muscle cells contain no glucose-6-phosphatase, GSD I causes no other neuromuscular effects. Mental retardation (abbreviated as MR), is a term for a pattern of persistently slow learning of basic motor and language skills (milestones) during childhood, and a significantly below-normal intellectual capacity as an adult. ...

Presentation and diagnosis

Several different problems may lead to the diagnosis, usually by two years of age:

• seizures or other manifestations of severe fasting hypoglycemia;
• hepatomegaly with abdominal protuberance;
• hyperventilation and apparent respiratory distress due to metabolic acidosis;
• episodes of vomiting due to metabolic acidosis, often precipitated by minor illness and accompanied by hypoglycemia.

Once the diagnosis is suspected, the multiplicity of clinical and laboratory features usually makes a strong circumstantial case. If hepatomegaly, fasting hypoglycemia, and poor growth are accompanied by lactic acidosis, hyperuricemia, hypertriglyceridemia, and enlarged kidneys by ultrasound, gsd I is the most likely diagnosis. The differential diagnosis list includes glycogenoses types III and VI, fructose 1,6-bisphosphatase deficiency, and a few other conditions (page 5), but none are likely to produce all of the features of gsd I.

The next step is usually a carefully monitored fast. Hypoglycemia often occurs within six hours. A critical blood specimen obtained at the time of hypoglycemia typically reveals a mild metabolic acidosis, high free fatty acids and -hydroxybutyrate, very low insulin levels, and high levels of glucagon, cortisol, and growth hormone. Administration of intramuscular or intravenous glucagon (0.25 to 1 mg, depending on age) or epinephrine produces little rise of blood sugar.

The diagnosis is definitively confirmed by liver biopsy with electron microscopy and assay of glucose-6-phosphatase activity in the tissue and/or specific gene testing, available in recent years.

Treatment

The primary treatment goal is prevention of hypoglycemia and the secondary metabolic derangements by frequent feedings of foods high in glucose or starch (which is readily digested to glucose). To compensate for the inability of the liver to provide sugar, the total amount of dietary carbohydrate should approximate the 24-hour glucose production rate. The diet should contain approximately 65-70% carbohydrate, 10-15% protein, and 20-25% fat. At least a third of the carbohydrates should be supplied through the night, so that a young child goes no more than 3-4 hours without carbohydrate intake

In the last 30 years, two methods have been used to achieve this goal in young children: (1) continuous nocturnal gastric infusion of glucose or starch; and (2) night-time feedings of uncooked cornstarch. An elemental formula, glucose polymer, and/or cornstarch can be infused continuously through the night at a rate supplying 0.5-0.6 g/kg/hr of glucose for an infant, or 0.3-0.4 for an older child. This method requires a nasogastric or gastrostomy tube and pump. Sudden death from hypoglycemia has occurred due to malfunction or disconnection, and periodic cornstarch feedings are now preferred to continuous infusion.

Cornstarch is an inexpensive way to provide gradually digested glucose. One tablespoon contains nearly 9 g carbohydrate (36 calories). Although it is safer, less expensive, and requires no equipment, this method does require that parents arise every 3-4 hours to administer the cornstarch. A typical requirement for a young child is 1.6 g/kg every 4 hours.

Long-term management should eliminate hypoglycemic symptoms and maintain normal growth. Treatment should achieve normal glucose, lactic acid, and electrolyte levels, and only mild elevations of uric acid and triglycerides.

Avoidance of other sugars

Intake of carbohydrates which must be converted to G6P to be utilized (e.g., galactose and fructose) should be minimized. Although elemental formulas are available for infants, many foods contain fructose or galactose in the forms of sucrose or lactose. Adherence becomes a contentious treatment issue after infancy.

Other therapeutic measures

Persistent elevation of uric acid above 6.5 mg/dl warrants treatment with allopurinol to prevent uric acid deposition in kidneys and joints.

Because of the potential for impaired platelet function, coagulation ability should be checked and the metabolic state normalized before surgery. Bleeding time may be normalized with 1-2 days of glucose loading, and improved with ddavp. During surgery, iv fluids should contain 10% dextrose and no lactate.

Treatment of acute metabolic acidosis episodes

The most significant acute problem in childhood is a vulnerability to episodes of metabolic acidosis precipitated by minor illnesses. If a vomiting illness persists longer than 2-4 hours, the child should be seen and assessed for dehydration, acidosis, and hypoglycemia. If these are developing, intravenous fluids should be provided at a rate above maintenance. For mild acidosis, an effective fluid is 10% dextrose in ½ normal saline with 20 mEq/l KCl, but if acidosis is severe, 75-100 mEq/l NaHCO3 and 20 mEq/l of K acetate can be substituted for the NaCl and KCl.

Natural history, prognosis, long term complications

Without adequate metabolic treatment, patients with gsd I have died in infancy or childhood of overwhelming hypoglycemia and acidosis. Those who survived were stunted in physical growth and delayed in puberty because of chronically low insulin levels. Mental retardation from recurrent, severe hypoglycemia is considered preventable with appropriate treatment.

Hepatic complications have been serious in some patients. Adenomas of the liver can develop in the second decade or later, with a small chance of later malignant transformation to hepatoma or hepatic carcinomas (detectable by -fetoprotein screening). Several children with advanced hepatic complications have improved after liver transplantation.

Additional problems reported in adolescents and adults with gsd I have included hyperuricemic gout, pancreatitis, and chronic renal failure. Despite hyperlipidemia, atherosclerotic complications have been infrequently reported.

With diagnosis before serious harm occurs, prompt reversal of acidotic episodes, and appropriate long-term treatment, most children will be healthy. With exceptions and qualifications, adult health and life span may also be fairly good, although lack of effective treatment before the mid-1970s has limited our long-term information.

References

Cornblath M, Schwartz R. Disorders of glycogen metabolism. In: Cornblath M, Schwartz R. Disorders of Carbohydrate Metabolism in Infancy. 3rd edition. Cambridge: Blackwell, 1991.

Chen Y-T, Burchell A. Glycogen storage diseases. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic Basis of Inherited Disease. 7th edition. New York: McGraw-Hill, 1995.

Tsalikian E, Haymond MW. Hypoglycemia in infants and children. In: Service FJ. Hypoglycemic Disorders: Pathogenesis, Diagnosis, and Treatment. Boston: G.K. Hall Medical Publishers, 1983.

See also

Links

E-medicine article on GSD I OMIM entry on GSD I

Links

The newsletter of this national family support network complements and corroborates the physician's information and recommendations. Association for Glycogen Storage Disease PO Box 896, Durant IA, 52747 (319) 785-6038