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Introduction
Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.

= Von Gierke Disease = Von Gierke disease, in simple terms, is a condition in which the body cannot break down glycogen. Glycogen is a form of sugar (glucose) that is stored in the liver and muscles. It is normally broken down into glucose to give you more energy when you need it. Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in humans, animals, and fungi. The polysaccharide structure represents the main storage form of glucose in the body.

In humans, glycogen is made and stored primarily in the cells of the liver and the muscles, hydrated with three or four parts of water. Glycogen functions as the secondary long-term energy storage

Von Gierke disease is also called Type I glycogen storage disease (GSD I).

The two major subtypes of glycogen storage disease type I (GSDI) are: The lack of either G6Pase catalytic activity or glucose-6-phosphate exchanger SLC37A4 (transporter) activity in the liver leads to inadequate conversion of glucose-6-phosphate into glucose through normal glycogenolysis and gluconeogenesis pathways, resulting in severe hypoglycemia and many other signs and symptoms of the GSDI disorders.
 * GSD type Ia, caused by the deficiency of glucose-6-phosphatase (G6Pase) catalytic activity;
 * GSD type Ib, caused by a defect in glucose-6-phosphate exchanger SLC37A4 (transporter).

Causes (and Inheritance)
Von Gierke disease occurs when the body lacks the protein (enzyme) that releases glucose from glycogen. This causes abnormal amounts of glycogen to build up in certain tissues. When glycogen is not broken down properly, it leads to low blood sugar.

This disease autosomal recessive metabolic disorders resulting in storage of abnormal amounts and/or forms of glycogen. Von Gierke disease is inherited, which means it is passed down through families. If both parents carry a nonworking copy of the gene related to this condition, each of their children has a 25% (1 in 4) chance of developing the disease.

Von Gierke disease is a GSD caused by defective liver and kidney glucose-6-phosphatase activity. The disease-causing mutation(s) can be either in the gene coding for the liver glucose-6-phosphatase enzyme (G6PC) or in the gene coding for the endoplasmic reticulum substrate and/or product transport proteins of the glucose-6-phosphatase system. The two common forms of GSD1 are termed GSD1a and GSD1b, and are caused by deficiency in G6PC and the glucose-6-phosphate transporter (G6PT1), respectively.

Symptoms
Signs and symptoms of this condition typically appear around the age of 3 or 4 months, when babies start to sleep through the night and do not eat as frequently as newborns.

Affected infants may have As they get older, children with GSDI have thin arms and legs and short stature. An enlarged liver may give the appearance of a protruding abdomen. The kidneys may also be enlarged. Affected individuals may also have diarrhea and deposits of cholesterol in the skin (xanthomas).
 * low blood sugar (hypoglycemia), which can lead to seizures
 * lactic acid in the body (lactic acidosis),
 * high blood levels of a waste product called uric acid (hyperuricemia)
 * excess amounts of fats in the blood (hyperlipidemia).

People with GSDI may experience delayed puberty.

Beginning in young to mid-adulthood, affected individuals may have
 * thinning of the bones (osteoporosis)
 * a form of arthritis resulting from uric acid crystals in the joints (gout)
 * kidney disease
 * high blood pressure in the blood vessels that supply the lungs (pulmonary hypertension)

Females with this condition may also have abnormal development of the ovaries (polycystic ovaries). In affected teens and adults, tumors called adenomas may form in the liver.

Adenomas are usually noncancerous (benign), but occasionally these tumors can become cancerous (malignant).

Diagnosis
Some of the diagnostic features/values of tests are as follows:

Signs of hypoglycemia, hepatomegaly, and growth failure

Laboratory findings:
 * Hypoglycemia - Fasting blood glucose concentration <60 mg/dL (reference range: 70-120 mg/dL)
 * Lactic acidosis - Blood lactate >2.5 mmol/L (reference range: 0.5-2.2 mmol/L)
 * Hyperuricemia - Blood uric acid >5.0 mg/dL (reference range: 2.0-5.0 mg/dL)
 * Hyperlipidemia
 * Triglycerides >250 mg/dL (reference range: 150-200 mg/dL); hypertriglyceridemia causes the plasma to appear “milky.”
 * Cholesterol >200 mg/dL (reference range: 100-200 mg/dL)
 * Glucagon or epinephrine challenge test - Administration of glucagon or epinephrine causes little or no increase in blood glucose concentration, but both increase serum lactate concentrations significantly.

Histopathologic liver findings - Distention of the liver cells by glycogen and fat

The diagnosis of GSDI is established by identification of either of the following:
 * Biallelic pathogenic variants in G6PC (GSDIa) or SLC37A4 (GSDIb) on molecular genetic testing
 * Deficient hepatic enzyme activity

Treatment
The disease is currently managed by nocturnal nasogastric infusion of glucose and/or cornstarch mixed into drinks during the day, but compliance is often low. Recent advances in the use of gene therapy in animal models of the disease provide hope for this approach in the treatment of human patients in the future.

The goal of treatment is to avoid low blood sugar. Eat frequently during the day, especially foods that contain carbohydrates (starches). Older children and adults may take cornstarch by mouth to increase their carbohydrate intake.

In some children, a feeding tube is placed through their nose into the stomach to provide sugars or uncooked cornstarch throughout the night. The tube can be taken out each morning.

A medicine to lower uric acid in the blood and decrease the risk for gout may be prescribed. Your provider may also prescribe medicines to treat kidney disease, high lipids, and to increase the cells that fight infection.

People with Von Gierke disease cannot properly break down fruit or milk sugar. It is best to avoid these products.