What causes glycogeneses?

The glycogenases la and lb type are inherited autosomally recessively. The gene encoding glucose-6-phosphatase (G6PC) is mapped on chromosome 17q21. More than 100 mutations were identified. The gene encoding the transport protein (G6PT) is mapped on chromosome llq23. About 70 different mutations are described.

Glycogenosis type III is an autosomal recessive disease caused by deficiency of amylo-1,6-glucosidase (debranching enzyme) (GDE). The defect of this enzyme leads to the accumulation of glycogen anomalous structure. The GDE gene is mapped on chromosome 1p21. Approximately 50 mutations of this gene were identified. Glycogenosis IIIb is usually caused by mutations of the third exon of the gene, while mutations in other regions, as a rule, lead to glycogenesis of Sha. Clear genophenotypic correlations between the severity of the mutation and the clinical manifestations of the disease have not been revealed.

Glycogenosis IV type is inherited autosomal recessive. The gene encoding the GBE enzyme is mapped on the chromosome of Sp. 14. Three point mutations - R515C, F257L and R524X - were found in the majority of patients with hepatic form of the disease. In patients with non-progressive hepatic form, a mutation of Y329S was detected. In the adult form of the disease, all mutations detected are relatively mild, which may explain the late manifestation of the disease.

Glycogenosis of type VI is an autosomal recessive disease associated with mutations of the hepatic isoform gene of glycogen phosphorylase. There are three isoforms of phosphorylase, which are encoded by different genes. The gene for the hepatic isoform of glycogen phosphorylase PYGL is mapped on chromosome 14q21-q22.

Glycogenosis IX type. Kinase phosphorylase (RNA) is a decahexameric protein consisting of four subunits. Two isoforms of the a-subunit (aL - hepatic and aM - muscle) are encoded by two genes located on the X chromosome (RNAA2 and RNKA1, respectively); beta-subunit (encoded by the RNKB gene ), two isoforms of the y-subunit (yT-liver / testes and yM-muscle, are encoded by the PKHG2 and PKHG1 genes respectively) and three isoforms of calmodulin (CALM1, CALM2, CALM3), encoded by autosomal genes. The RNKA2 gene is mapped to Chp22.2-p22.1, the RNAV gene on 16ql2-ql3, and the PKHG2 gene on the 16p12-p11 chromosome.

The most frequent hepatic variant, XLG or GSD IXa (due to mutations in the RNA2 gene ) is divided into two subtypes: XLG 1, classical, frequent, and XLG 2. With XLG 1, the activity of RNA in the liver and blood cells is reduced, with XLG 2 activity RNA in the liver, erythrocytes and leukocytes is normal. Therefore, even the normal activity of this enzyme does not exclude the glycogenesis of XLG. This is due to the fact that XLG 2 is due to mutations that have a regulatory effect on the enzyme activity, but do not alter its activity in vitro.

Glycogenosis of type 0 is an autosomal recessive disease caused by mutations in the glycogen synthase gene. The glycogen synthase gene (GYS2) is mapped on chromosome 12p12.2.

Glycogenosis type II, or Pompe disease, is inherited autosomal recessively. The gene encoding a-glycosidase (GAA) is mapped on chromosome 17q25. More than 120 mutations are known. For some mutations, clear gene-phenotypic correlations are established, for example, the mutation of the splice site IVSI (-13T-> G) occurs in more than half of patients with late disease.

Glycogenosis of type V

Autosomal recessive disease associated with mutations of the myophosphorylase gene. The myophosphorylase gene (PYGM) is mapped on the chromosome llql3. There are more than 40 mutations. The most common mutation is R49X, 81% of the mutant alleles in Europe. Genophenotypic correlations have not been revealed - in patients with the same genotype there may be a more severe or more mild course of the disease.

Glycogenosis type VII

Autosomal recessive disease caused by mutations of the PFK-M gene . The PFK-M gene is mapped on chromosome 12, it encodes the muscle subunit of phosphofructokinase. At least 15 mutations are described in the PFK-M gene in patients with PFK deficiency.

Glycogenosis IIb type

Coupled with the X chromosome is a dominant disease associated with a deficiency of LAMP-2 (lysosomal-associated membrane protein 2). The LAMP2 gene is mapped to Xq28.

Insufficiency of phosphoglycerate kinase

Phosphoglycerate kinase (PGK) is a protein encoded by the PGK1 gene . The gene is mapped to Xql3.

Glycogenosis of the XI type, or deficiency of lactate dehydrogenase, is an autosomal recessive disease. Lactate dehydrogenase, a tetrameric enzyme composed of two subunits of M (or A) and H (or B), is represented by 5 isoforms. The gene of the M-subunit of LDHM is mapped on chromosome 11.

G type glycogenesis, or phosphoglycerate mutase deficiency (PGAM), is an autosomal recessive disease. Phosphoglycerate mutase is a dimeric enzyme: different tissues contain different proportions of the muscle (MM) or brain isoform (BB) and hybrid variants (MB). In the muscle tissue, the MM isoform predominates, while in most other tissues it is BB. The PGAMM gene is mapped on chromosome 7 and encodes the M subunit.

Glycogenosis XII type, or deficiency of aldolase A, is an autosomal recessive disease. Aldolase has three isoforms (A, B, C): skeletal muscles and erythrocytes contain predominantly the A-isoform, which is encoded by the ALDOA gene . The gene is mapped on chromosome 16.

Glycogenosis XIII type or insufficiency beta enolase, - an autosomal recessive disease, beta-enolase - dimeric enzyme which exists in several isoforms, formed by the combination of three subunits, a, beta and beta-subunit is encoded by a gene EN03, charted on chromosome 17.