Fundamentals of Medical Genetics - Buzhyievska T.I. 2001

Genetic disorders
Amino acid metabolism disorders

In the vast majority of cases, this is an autosomal recessive disorder.

Alcaptonuria is the first enzymopathy described in humans. It manifests as dark urine immediately after birth. Subsequently, due to the accumulation of homogentisic acid in Tissues, the sclera and mucous membranes darken. At the age of 10–12 years, ochronotic Arthritis and cardiovascular diseases develop. As a result of a genetic defect in homogentisate oxidase, the METABOLISM of Phenylalanine and Tyrosine is disrupted. Alcaptonuria is inherited in an AR manner. Its Treatment includes restricting dietary Phenylalanine and Tyrosine, and administering high doses of ascorbic acid to enhance oxidative processes.

Phenylketonuria is a disorder of phenylalanine metabolism occurring at its earlier stages. It manifests in the first months of life (most commonly at 6–9 months of age) with developmental delay. The child has fair Hair and eyes (due to impaired pigment synthesis), and Skin pigmentation is absent. Oligophrenia, convulsive syndrome, and a characteristic musty odor are observed. Eczema, dermatitis, photosensitivity, pastiness, strabismus, and nystagmus are also frequently present. The disease is caused by the absence or reduced activity of the enzyme phenylalanine 4-hydroxylase. Pathomorphological examination reveals glial degeneration of the Brain. Phenylketonuria is inherited in an AR manner. Newborn mass screening is employed for preclinical detection. With early Structure/175.html">Implementation of a phenylalanine-restricted diet (dietary products such as Berlafen, Cymogran, Minafen, Aponti) and strict medical supervision, the child's physical and mental development proceeds normally. Without dietary therapy, severe mental retardation and idiocy develop in 100% of cases. More than one percent of individuals of Slavic descent are carriers of the mutant Gene.

Argininemia manifests with convulsions and vomiting shortly after birth. Later, hepatosplenomegaly, microcephaly, paraparesis, and mental and physical developmental delay join the clinical picture. The concentration of Arginine in the Blood and CEREBROSPINAL FLUID is elevated. Carriage of the Shope papilloma virus, which synthesizes arginase, leads to a decrease in blood arginine levels. Argininemia is inherited in an AR manner.

Albinism is a group of disorders caused by a defect in melanin metabolism, where melanin is synthesized from tyrosine. Tyrosinase-positive and tyrosinase-negative albinism (associated with hemorrhagic diathesis) are distinguished. There are forms of the disease accompanied by deafness as well as normal Hearing. It is inherited in an AD, AR, or XR manner.

In addition to the aforementioned AMINO ACID METABOLISM disorders, there are aminoacidemias associated with defects in the body's transport systems, specifically with Genetic Defects in the Urinary Organs.

Celiac disease is a hereditary pathology that occurs quite frequently (1:3000). It is associated with a deficiency of Enzymes that break down gliadin, a component of the gluten protein found in wheat, rye, barley, and oats—that is, all cereal grains. The condition manifests after the Introduction of complementary foods such as porridge and bread, mostly toward the end of the first year of life. Due to the Toxic Effect of glutamine peptide, the ciliated epithelium of the intestine is destroyed in patients. The absorption of all nutrients is impaired. Enteropathy, dehydration, frequent loose stools, and hypotrophy are observed. Celiac disease is inherited in an AR manner. Treatment consists of excluding porridges (semolina, oatmeal, pearl barley) and bread from the diet.

Nowadays, there are agliadin grains developed through the Selection of varieties mutated at the corresponding gene. Products made from such groats and flour can be given to children suffering from celiac disease.