Gierke's disease: what is it, causes, symptoms, treatment, prognosis

What is Gierke's disease?

Gierke's disease (other names, von Gierke's glycogenosis, glycogenosis type I) refers to diseases of glycogen accumulation, which is a group of disorders in which accumulated glycogen does not can be metabolized to glucose to supply energy and maintain stable blood glucose levels for organism.

Gierke's disease is inherited as an autosomal recessive genetic disorder. Type I glycogenosis is characterized by the accumulation of excess glycogen and fat in the liver and kidneys, which can lead to enlargement of the liver and kidneys and stunted growth, leading to low growth.

Gierke's disease is caused by mutations in G6PC gene (type Ia) or SLC37A4 gene (type Ib). These mutations lead to a deficiency of enzymes that block the breakdown of glycogen in the affected organs, causing excessive accumulation of glycogen and fat in body tissues and low levels of circulating glucose in blood. An enzyme deficiency also leads to an imbalance or excessive accumulation of other metabolites, especially lactates, uric acid, and fats such as lipids and triglycerides.

Signs and symptoms

The main symptom of Gierke's disease in infancy is low blood sugar (hypoglycemia). Symptoms of Gierke's disease usually begin between 3 and 4 months of age and include an enlarged liver (hepatomegaly), kidney (nephromegaly), increased levels of lactate, uric acid and lipids (both total lipids and triglycerides) and possible seizures caused by repeated episodes of hypoglycemia. Continued low blood sugar can lead to stunted growth and development and muscle weakness. Affected children usually have:

• doll-like faces with thick cheeks (see. photo above);
• relatively thin limbs;
• short stature;
• bulging belly.

High lipid levels can lead to the formation of oily skin growths called xanthomas. Other conditions that may be associated with an untreated medical condition include:

• osteoporosis;
• delayed puberty;
• gout (arthritis caused by uric acid build-up);
• kidney disease;
• pulmonary hypertension (high blood pressure in the arteries that supply the lungs);
• liver adenoma (benign liver tumors);
• polycystic ovary disease in women;
• inflammation pancreas (pancreatitis);
• diarrhea;
• changes in brain function due to repeated episodes of hypoglycemia.

Impaired platelet function can lead to bleeding tendencies with frequent nosebleeds. In general, patients with type Ib glycogenosis have similar clinical manifestations to those of type Ia patients, but in addition to the aforementioned manifestations, the disease is also associated with impaired function of neutrophils and monocytes, as well as with chronic neutropenia after the first few years of life, leading to recurrent bacterial infections and ulcers of the oral and intestinal mucosa.

Early diagnosis and effective treatment can lead to normal growth and puberty, and many affected people live to adulthood and lead normal lives. Many patients have had successful pregnancies and childbirth.

Causes

Gierke's disease is associated with abnormalities in two genes. Gene mutations G6PC lead to a deficiency of the enzyme glucose-6-phosphatase (G6Pase) and account for approximately 80% of diseases. This type of pathology is called Gierke's disease type Ia. Gene mutations SLC37A4 lead to a deficiency of the enzyme translocase glucose-6-phosphatase (transporter deficiency) and account for approximately 20% of diseases. This type of disease is called Gierke's disease type Ib. Both of these enzyme deficiencies cause excess glycogen and fat to accumulate in body tissues.

The pathology is inherited as an autosomal recessive genetic disorder. Recessive genetic disorders occur when a person inherits a non-working gene from each parent. If a person receives one working gene and one non-working gene for the disease, the person will be a carrier of the disease, but usually asymptomatic. The risk for two carrier parents to pass on both non-working genes and therefore conceive a sick child is 25% in every pregnancy. The risk of having a child who will be a carrier, like the parents, is 50% with each pregnancy. The probability for a child to receive working genes from both parents is 25%. The risk is the same for men and women.

Affected populations

Von Giercke's glycogenosis occurs in about 1 in 100,000 newborns. The prevalence of the disease among Ashkenazi Jews is approximately 1 in 20,000. Pathology affects men and women in equal numbers in any given population group.

Symptomatic disorders

Symptoms of the following disorders may be similar to those of Gierke's disease. Detailed assessments can be useful for differential diagnosis:

• Forbes disease or measles (type III glycogenosis) is a type of glycogen storage disease that is inherited in an autosomal recessive manner. Symptoms are caused by a deficiency of the enzyme amylo-1,6-glucosidase. This enzyme deficiency causes excessive amounts of improperly metabolized glycogen (a stored form of energy that comes from carbohydrates), which is deposited in the liver, muscles and, in some cases, in the heart. Symptoms become apparent in the first years of life with hepatomegaly and / or myopathy and elevated liver enzymes. In the first few months, some of the symptoms may coincide with Gierke's disease (high lipids, hepatomegaly, low glucose).
• Andersen's disease (type IV glycogenosis). This type is also inherited as an autosomal recessive trait. The disease is caused by insufficient activity of the glycogen-branching enzyme, which leads to the accumulation of glycogen in the liver, muscles and / or other tissues. In most affected individuals, symptoms and signs become apparent in the first few years of life. Signs usually include an inability to grow and gain weight at the expected rate (inability to develop) and an abnormal enlargement of the liver and spleen (hepatosplenomegaly).
• Hers's or Hers's disease (type VI glycogenosis). This pathology usually has milder symptoms than most other diseases associated with glycogen storage. Pathology is caused by a deficiency of the liver phosphorylase enzyme. This disease is characterized by an enlarged liver (hepatomegaly), moderately low blood sugar (hypoglycemia), elevated blood levels of acetone and other ketone bodies (ketosis), and moderate retention growth. Symptoms are not always obvious during childhood and children can usually lead normal lives. However, in some cases, the symptoms can be severe.
• Haga disease (type IX glycogenosis) arises from a deficiency of the enzyme phosphorylase kinase. It can be inherited as an X-linked genetic disease caused by a deficiency of the liver kinase phosphorylase enzyme (mainly the gene PHKA2), or it can be inherited as an autosomal recessive form (caused by genes PHKG2 and PHKB) causing liver disease and / or muscles. The disorder is characterized by slightly low blood sugar levels (hypoglycemia). Excess glycogen (a stored form of energy that comes from carbohydrates) is stored in the liver, causing the liver to enlarge (hepatomegaly).
• Hereditary fructose intolerance (HFF) Is an autosomal recessive genetic condition that causes an inability to digest fructose (fruit sugar) or its precursors (sugar, sorbitol, and brown sugar). The disease is associated with a deficiency in the activity of the enzyme fructose-1-phosphate aldolase (aldolase B), which leads to the accumulation of fructose-1-phosphate in the liver, kidneys and small intestine. Fructose and sucrose are natural sugars that are used as sweeteners in many foods, including baby food. This disorder can be life-threatening in children and ranges from mild to severe in older children and adults.

Diagnostics

Von Gierke's glycogenosis is diagnosed by laboratory tests that indicate abnormal levels of glucose, lactate, uric acid, triglycerides, and cholesterol. Molecular genetic testing of genes is available to confirm the diagnosis. G6PC and SLC37A4. Molecular genetic testing can also be used for carrier identification and prenatal diagnosis. Liver biopsy can also be used to prove the deficiency of specific enzymes of glycogenosis type Ia.

Standard treatments

Gierke's disease is treated with a special diet to maintain normal glucose levels, prevent hypoglycemia, and maximize growth and development. Give frequent small amounts of carbohydrates day and night throughout your life. Calcium supplements may be recommended to avoid deficiency. vitamin D and iron. Frequent consumption of raw cornstarch is recommended to maintain and improve blood glucose levels.

Allopurinol, a drug that can lower blood uric acid levels, may be helpful in controlling the symptoms of gouty arthritis during adolescence.

Drugs may be prescribed to lower lipid levels and prevent and / or treat kidney disease.

Granulocyte-macrophage colony-stimulating factor (GM-CSF) can be used to treat recurrent infections in patients with type Ib glycogenosis.

Liver tumors (adenomas) can be treated with a small surgery or a procedure in which the adenomas are removed using heat and current (radio frequency ablation). Kidney and / or liver transplants are sometimes considered if other treatments are unsuccessful or if liver adenomas continue to grow.

Individuals with Giercke's disease should be monitored at least once a year by ultrasound of the kidneys and liver, and blood tests should be done regularly.

Forecast

Patients who receive appropriate treatment have a reasonably normal life expectancy.