MEDICAL BIOLOGY, HUMAN ANATOMY, PHYSIOLOGY AND PATHOLOGY - Ya.I.Fedoniuk 2010

BIOLOGY

SECTION 1. BIOLOGICAL BASES OF HUMAN VITAL ACTIVITY

1.4. ONTOGENETIC LEVEL OF LIFE ORGANIZATION

1.4.2. Fundamentals of human genetics

Enzymopathies

The largest group of Gene disorders consists of enzymopathies (inborn errors of METABOLISM), which are metabolic diseases caused by enzyme defects. The Molecular Basis of hereditary enzymopathies is enzyme deficiency resulting from Mutations in the genes that control the synthesis of these Enzymes. The enzyme either alters its Structure and Functional properties or fails to form altogether. In such cases, the biochemical reaction catalyzed by this enzyme is blocked. This may result in: 1) insufficient production of the products of this reaction or its downstream metabolites; 2) accumulation in the body of the blocked reaction substrate or its precursors; 3) a shift in the primary metabolic pathway and increased production of byproducts that are normally present in negligible amounts.

The Classification of inherited Metabolic Disorders is based on the Chemical Nature of the substances involved. They include:

1) inherited Amino acid metabolism disorders — phenylketonuria, albinism, alkaptonuria, maple syrup urine disease, homocystinuria;

2) inherited Carbohydrate Metabolism disorders — galactosemia, fructosemia, Glycogen Storage Diseases;

3) inherited Lipid Metabolism disorders — plasma lipoidosis, Tay-Sachs disease (amaurotic idiocy);

4) inherited purine and pyrimidine metabolism disorders — Lesch-Nyhan syndrome;

5) inherited metal metabolism disorders.

Diagnosis of enzymopathies is carried out using Biochemical Methods. Early diagnosis and pharmacological or dietary intervention make it possible to treat and prevent The Development of these hereditary disorders.

Phenylketonuria is an inherited metabolic disorder (enzymopathy) caused by a genetic deficiency of the enzyme phenylalanine hydroxylase, which is required to convert The amino acid phenylalanine into Tyrosine. This leads to the accumulation of phenylalanine, phenylpyruvate, and phenylacetate in the Blood, CEREBROSPINAL FLUID, and Tissues, exerting a toxic effect on the Central Nervous system. Children are born healthy, but with the intake of phenylalanine from breast milk, mental retardation gradually develops. Since impaired phenylalanine metabolism leads to decreased tyrosine levels, patients exhibit reduced pigmentation of the Skin, Hair, and iris. The frequency of phenylketonuria in European populations averages 1:10,000 newborns. The inheritance pattern is autosomal recessive. The phenylalanine hydroxylase gene is located on chromosome 12.

Clinical diagnostic features: fair hair, blue eyes, unpigmented skin, "mousy" odor (due to The excretion of phenylalanine in urine); after 6 months — lethargy, apathy, loss of all acquired psychomotor Functions, seizures, and progressive mental retardation ranging to idiocy.

The diagnosis is established based on clinical examination and biochemical detection of phenylpyruvate in urine and phenylalanine in blood. Treatment involves diet therapy: exclusion of foods containing phenylalanine (eggs, meat, milk) from the diet. Early diagnosis and dietary management prevent the Development of the clinical picture of the disease.

Albinism is an inherited metabolic disorder (enzymopathy) caused by a deficiency of the enzyme tyrosinase, which catalyzes the reactions necessary for the synthesis of dark pigments, known as Melanins. The absence of melanin in skin melanocytes manifests as insufficient (or absent) pigmentation of the skin and hair, increased sensitivity of the skin to sunlight, and visual impairment. The inheritance pattern is autosomal recessive.

Alkaptonuria is an inherited disease with an Autosomal Recessive Inheritance pattern, caused by a genetically determined deficiency of homogentisic acid oxidase. A characteristic manifestation of the disease is the excessive excretion of homogentisic acid in the urine, which turns dark upon The addition of alkalis. Homogentisic acid accumulates in Connective Tissue. Articular Cartilage acquires a yellow-orange color (ochronosis), the cartilage of the auricles and Nose darkens, and Arthritis develops.