Textbook - BIOLOGICAL CHEMISTRY - Gubsky Yu.I. - 2000

Chapter III. METABOLISM OF MAJOR CLASSES OF BIOMOLECULES

CHAPTER 13. CARBOHYDRATE METABOLISM. III. GLYCOGEN AND GLYCOCONJUGATE METABOLISM

13.3. GENETIC DISORDERS OF GLYCOGEN METABOLISM

Hereditary disorders of Glycogen breakdown or synthesis manifest as enzymopathies, specifically Glycogen Storage Diseases (glycogenoses) and aglycogenoses.

Class="center">Glycogenoses

Glycogenoses are hereditary disorders whose molecular basis is an innate deficiency in the Synthesis of specific Enzymes involved in Glycogenolysis, caused by defects in the cellular genetic system. In glycogenoses, Internal Organs and Tissues (primarily the Liver, Muscles, and Blood Cells) exhibit an accumulation of abnormally excessive amounts of glycogen—sometimes with an altered molecular Structure—that cannot be utilized in metabolic processes (Table 13.2).

Table 13.2. Biochemical characteristics of glycogenoses (adapted from R. Berkow (Ed.): The Merck Manual of Diagnosis and Therapy, 1992, with modifications)

Clinically, glycogenoses manifest as severe hypoglycemia resulting from the inability of liver glycogen to break down and release glucose molecules. Glycogenoses involving impaired enzyme systems for liver glycogen mobilization are characterized by hepatomegaly, fatty degeneration of hepatocytes, and cirrhosis. Deficiency of glycogenolytic enzyme systems in muscles is accompanied by cramps during physical exertion.

Aglycogenoses

Aglycogenoses are hereditary disorders of glycogen storage whose molecular basis involves genetic defects that disrupt The formation of the glycogen synthase enzyme.

Due to glycogen synthase deficiency, hepatocytes are unable to form glycogen reserves, and intracellular glycogen concentration is significantly reduced. Because of this lack of glycogen reserves, patients with aglycogenoses—much like those with glycogenoses—suffer from profound hypoglycemia, particularly in the fasting state or after a long interval following dietary glucose intake. Hypoglycemia in aglycogenoses can lead to severe coma due to cerebral energy deprivation. Such patients typically die in early childhood.