Glycogenoses in children

Glycogen metabolism disorders are hereditary diseases associated with defects in glycogen breakdown, gluconeogenesis, and glycogen synthesis. All of them are called "glycogenoses", although not all of them involve disturbances in the processes of glycogen breakdown.

ICD-10 code

• E74.0 Glycogen storage diseases.
• E74.4 Disorders of pyruvate metabolism and gluconeogenesis.

Epidemiology

Glycogenosis type I is a rare hereditary metabolic disease. The incidence of the disease is 1 in 50,000-100,000 live births.

Glycogenosis type III, glycogenosis type IV, glycogenosis type V, glycogenosis type VI, glycogenosis type VII - the incidence is not precisely established; these are rare hereditary metabolic diseases.

Glycogenosis type IX - the exact frequency has not been established. One of the most common types of glycogenoses.

Glycogenosis type II - depending on the country and ethnicity, the incidence of this disease varies from 1 in 14,000 to 1 in 300,000. The infantile form of Pompe disease is quite common among African Americans, as well as in southern China and Taiwan, while the adult form of the disease is common in the Netherlands. The overall incidence is estimated at 1 in 40,000.

Glycogenosis type XI - there are descriptions of five cases of this disease in the literature.

Glycogenosis type X - about ten patients with this form of glycogenosis have been described.

Glycogenosis type XII - there is only one description of a patient with this disease in the literature.

Glycogenosis type XIII - described in one patient.

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Causes of glycogenosis

Glycogenoses are caused by deficiencies of enzymes involved in the synthesis or breakdown of glycogen; the deficiency may occur in the liver or muscle and cause hypoglycemia or deposition of abnormal amounts or types of glycogen (or its intermediate metabolites) in tissues.

Glycogenosis diseases are inherited in an autosomal recessive manner, with the exception of glycogen storage disease type VIII/IX, which is inherited in an X-linked manner. The incidence is approximately 1/25,000 births, but may be higher because mild subclinical forms may remain undiagnosed.

What causes glycogen storage disease?

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Pathogenesis of glycogenoses

Glycogenosis type I

Glucose-6-phosphatase catalyzes the final reaction of both gluconeogenesis and glycogen hydrolysis and hydrolyzes glucose-6-phosphate into glucose and inorganic phosphate. Glucose-6-phosphatase is a special enzyme among those involved in liver glycogen metabolism. The active center of glucose-6-phosphatase is located in the lumen of the endoplasmic reticulum, which necessitates the transport of all substrates and reaction products through the membrane. Therefore, enzyme or substrate carrier protein deficiency leads to similar clinical and biochemical consequences: hypoglycemia even with the slightest starvation due to blockade of glycogenolysis and gluconeogenesis and to the accumulation of glycogen in the liver (as a consequence - liver cirrhosis ), kidneys and intestinal mucosa, leading to dysfunction of these organs.

Pathogenesis of glycogenoses

Symptoms of glycogenosis

Age of onset, clinical manifestations, and their severity vary depending on the type, but symptoms most often include signs of hypoglycemia and myopathy. Diagnosis is suspected based on history, physical examination, and detection of glycogen and intermediate metabolites in tissues by MRI and biopsy.

Symptoms of glycogenosis

Classification of glycogenoses

Glycogen is a branched homopolymer of glucose with a "tree-like" structure. Glucose residues are linked by an alpha (1-"4)-glycosidic bond, and at the branching points - by an alpha (1-"6)-glycosidic bond. Glycogen is stored in the liver and muscles. Liver glycogen serves primarily to maintain the level of glucose in the blood, while in muscles it is a source of hexose units used during glycolysis in the organ itself. There are 12 known forms of glycogenoses, the most common of them in children are types I, II, III, IX, and in adults - type V. The total frequency of glycogenoses is 1:20,000 live newborns. Glycogenoses are divided into two large groups - with predominant liver damage and with predominant muscle tissue damage. According to the accepted classification, each of the glycogenoses is assigned a number reflecting the sequence of their description.

Classification of glycogenoses

Diagnosis of glycogenoses

The diagnosis is confirmed by a marked decrease in enzyme activity in the liver (I, III, VI and VII I/IX types), muscles (IIb, III, VII and VIII/IX types), skin fibroblasts (types Ia and IV) or erythrocytes (type VII) or the absence of an increase in lactate in venous blood during forearm movement/ischemia (types V and VII).

Glycolysis defects (rare) may lead to syndromes resembling glycogenoses. Deficiencies of phosphoglycerate kinase, phosphoglycerate mutase, and lactate dehydrogenase resemble myopathies in glycogenoses types V and VII; deficiency of glucose transport protein 2 (Fanconi-Bickel syndrome) clinically resembles hepatopathy in other types of glycogenoses (e.g., I, III, IV, VI).

Diagnosis of glycogenoses

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Treatment of glycogenosis

Prognosis and treatment vary depending on the type, but treatment typically involves supplementing the diet with cornstarch to provide a constant source of glucose in the hepatic forms of glycogen storage disease and avoiding physical activity in the muscular forms.

Treatment of glycogenosis