Glycogenosis in children

Disorders of glycogen exchange are hereditary diseases associated with defects in glycogen cleavage, gluconeogenesis, and glycogen synthesis. All of them are called "glycogenoses", although not all processes of disintegration of glycogen are violated.

ICD-10 code

• E74.0 Diseases of accumulation of glycogen.
• E74.4 Infringements of exchange of pyruvate and gluconeogenesis.

Epidemiology

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

Glycogenosis III type, type IV glycogenosis, type V glycogenosis, type VI glycogenosis, type VII glycogenosis - the incidence is not exactly established; this is a rare hereditary metabolic disease.

Glycogenosis IX type - the exact frequency is not established. One of the most frequent variants of glycogenoses.

Glycogenosis type II - depending on the country and ethnicity, the frequency of this disease varies from 1 to 14 000 to 1 per 300 000. Infantile form of Pompe disease is quite common among African Americans, as well as in South China and Taiwan, while the adult the form of the disease is in Holland. The total frequency is estimated as 1 per 40 000.

Glycogenosis XI type - in the literature, five cases of this disease are described.

Glycogenosis of type X - about ten patients with this form of glyco-genesis are described.

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

Glycogenosis XIII type - described in one patient.

[1], [2], [3], [4], [5], [6], [7]

Causes of glycogenases

Glycogenoses are caused by a deficiency of enzymes involved in the synthesis or cleavage of glycogen; a deficiency can occur in the liver or muscles and cause hypoglycemia or the deposition of abnormal amounts or types of glycogen (or its intermediate metabolites) in tissues.

Glycogenoses are inherited in an autosomal recessive type, with the exception of glycogenase type VIII / IX, which is inherited in an X-linked type. The frequency is about 1/25 000 births, but it can be more, since mild subclinical forms may remain undiagnosed.

What causes glycogeneses?

[8], [9], [10], [11], [12], [13]

Pathogenesis of glycogeneses

Glycogenosis type I

Glucose-6-phosphatase catalyzes the final reaction of both gluconeogenesis and glycogen hydrolysis and carries out the hydrolysis of glucose-6-phosphate to glucose and inorganic phosphate. Glucose-6-phosphatase is a special enzyme among the liver involved in the metabolism of glycogen. 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, the inadequacy of the enzyme or the carrier protein of the substrate leads to similar clinical and biochemical consequences: hypoglycemia, even with the slightest starvation due to the blockade of glycogenolysis and gluconeogenesis, and the accumulation of glycogen in the liver (as a consequence - cirrhosis of the liver ), kidney and intestinal mucosa, leading to dysfunction these bodies.

Pathogenesis of glycogeneses

Symptoms of glycogenases

Age of onset, clinical manifestations and their severity vary depending on type, however the symptoms most often include signs of hypoglycemia and myopathy. The diagnosis is suspected based on anamnesis, examination and detection of glycogen and intermediate metabolites in tissues with MRI and biopsy.

Symptoms of glycogenases

Classification of glycogenases

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

Classification of glycogenases

Diagnosis of glycogenases

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 (Ha and IV types) or erythrocytes (VII type) or lack of increase in lactate in venous blood during movements / ischemia of the forearm (V and VII types).

Defects of glycolysis (rarely) can lead to the appearance of syndromes similar to glycogeneses. Deficiency of phosphoglycerate kinase, phosphoglycerate mutase and lactate dehydrogenase are similar to myopathies in glycogenases of V and VII types; deficiency of protein 2, involved in glucose transport (Fanconi-Bickel syndrome), clinically resembles hepatopathy in other types of glycogenes (eg, I, III, IV, VI).

Diagnosis of glycogenases

[14], [15], [16], [17]

Treatment of glycogenases

The prognosis and treatment vary depending on the type, but the treatment usually involves enriching the food with corn starch to provide a constant source of glucose in the hepatic forms of glycogenosis, as well as the exclusion of physical activity in muscle forms.

Treatment of glycogenases