Basics of Medical Genetics - Buzhyievska T.I. 2001

Hereditary diseases
Pathology of carbohydrate metabolism

An AD inheritance pattern for these disorders is extremely rare. The vast majority of syndromes are inherited in an AR manner (such as Glycogen Storage Diseases, galactosemias, hyperbilirubinemias, etc.). Diabetes Mellitus is classified among the genetically heterogeneous group of Carbohydrate METABOLISM disorders.

Aglycogenosis (hyperglycemic seizures) is characterized by severe hypoglycemia, morning seizures, and a complete lack of hepatic glycogen. The primary biochemical defect involves impaired Enzymes responsible for glycogen synthesis: glycogen synthetase and uridine diphosphate glucose-glycogen transferase. Seizure episodes are prevented through frequent feedings, including at night. Aglycogenosis is inherited in an AR fashion.

Galactosemia manifests shortly after birth with vomiting, jaundice, hepatomegaly, and ascites. Cataracts develop later in life, accompanied by delayed GROWTH AND DEVELOPMENT.

Biochemical analysis reveals galactosemia along with reduced activity of galactose-1-phosphate uridyltransferase in erythrocytes and Tissues. Galactosemia is also inherited in an AR manner. Children who are homozygous for this mutation cannot tolerate milk, and infants typically refuse breastfeeding. Treatment involves dietary management using milk-free formulas.

Galactokinase deficiency also presents with galactose intolerance. The Clinical symptoms of galactosemia and galactosuria mirror those of the aforementioned enzymopathy. It is inherited in an AR pattern. Treatment requires the exclusion of milk from the diet.

Beckwith-Wiedemann syndrome is characterized by fetal gigantism and hypoglycemia. Its Pathogenesis remains unclear, though it may be linked to an enzymopathy within glycogen metabolism. All possible inheritance patterns have been reported (predominantly AD), and The Role of Genomic Imprinting in the pathogenesis of this syndrome is currently being discussed. The condition manifests at birth with macrosomia, macroglossia, umbilical hernia, and earlobe creases. Clinical findings include hypoglycemia, hyperlipidemia, hypercholesterolemia, and hypocalcemia. Moderate intellectual disability develops over time. Treatment involves dietary management and surgical correction of birth defects.

Neonatal hypoglycemia is marked by infant hypertrophy, making affected newborns resemble infants born to mothers with diabetes mellitus. Clinical manifestations include seizures, hypoglycemia, and muscular hypotonia. This disorder is inherited in an AR pattern, and its pathogenesis is unknown. Idiopathic familial hypoglycemia manifests before the age of two, occurring more frequently in boys. Symptoms include lethargy, diaphoresis, increased appetite, tremors, seizures, and potential coma. The condition can be triggered by leucine. Defects in insulinase, which delays Insulin degradation, are suspected.

Diabetes mellitus is a genetically heterogeneous pathology that can result from autoimmune processes driven by Mutations in HLA system genes, mutations in the structural and regulatory Regions of the insulin Gene, Cell membrane receptor defects, circulating insulin inhibitors in the Blood, increased insulin degradation, or other genetic defects and various combinations thereof.

Great hopes are pinned on biotechnology Methods for treating this condition (genetically engineered insulin, direct gene correction).