Fundamentals of Medical Genetics - Buzhyievska T.I. 2001

Hereditary diseases
Hereditary defects of non-enzymatic proteins

This group primarily includes hereditary neuromuscular disorders, which are exceptionally heterogeneous by nature; these are myopathies and myodystrophies that develop As a result of damage to Muscle structures or neural elements. Among progressive muscular dystrophies, X-linked disorders caused by various Mutations in the dystrophin Gene are the most thoroughly studied.

Duchenne muscular dystrophy is characterized by an early onset of clinical symptoms: the child becomes inactive and avoids games; by the age of 3 to 5 years, climbing stairs becomes difficult, and over the next 5 to 10 years, mobility is completely lost. Pseudohypertrophy of the calf Muscles develops due to the replacement of muscle structures with Connective Tissue, and The Heart muscles are also affected. In Blood serum, elevated levels of creatine kinase and creatine phosphokinase activity can be detected as early as the onset of clinical manifestations. However, this is a secondary biochemical marker indicating a disruption in muscle Cell membranes. As the clinical manifestations of myodystrophy progress and the patient's condition worsens, the activity level of creatine kinase in the blood decreases. The inheritance pattern is XR. DNA Diagnostics for this pathology is available, which also enables prenatal diagnostics using fetal Tissues.

Becker muscular dystrophy differs from the previous form by a later clinical onset at 20-30 years of age, a prolonged and benign course (without loss of mobility or cardiac involvement), less pronounced pseudohypertropy compared to Duchenne muscular dystrophy, and milder biochemical abnormalities. This hereditary disease is caused by a mutation in the same dystrophin gene, located in a different and shorter region. In other words, Duchenne and Becker myopathies are different allelic forms of the same genetic pathology. The inheritance pattern is XR. DNA diagnostics and prenatal Diagnosis are available.

The Treatment of myopathies is currently symptomatic, aimed at improving muscle trophism (amino acid complexes, ATP, Vitamins B and E, anticholinesterase agents, blood transfusions, and local stimulating therapy).

Cystic fibrosis, or mucoviscidosis (of the Pancreas), is a hereditary disease caused by a mutation in the gene encoding the transmembrane conductance regulator protein, which is responsible for The transport of sodium, chloride, and Water across cell membranes. For the first time in history, using molecular biology Methods (reverse genetics), the gene was discovered and localized on chromosome 7q31.1, and numerous mutations within this gene were identified and deciphered, which in a homozygous state or as compound heterozygotes (two different mutant alleles) cause the disease. At the same time, the primary biochemical defect—the product of this gene's expression—remained unknown. The disease has a prevalence of 1:2000 – 2500 newborns. The clinical course can begin in the neonatal period with a very severe symptom complex known as meconium ileus, where a thick and viscous meconium plug causes intestinal obstruction and all its subsequent complications. Subsequently, During the first 6 months of life, the clinical picture of cystic fibrosis develops, which may be dominated by spontaneous pulmonary lesions (pulmonary form), gastrointestinal involvement (intestinal form), or mixed symptoms. In all forms of the disease, secretory processes are impaired in the corresponding Cells of all exocrine glands. Patients experience breathing difficulties, pertussis-like spasmodic cough, chronic bronchopulmonary inflammation, emphysema, and Pulmonary Atelectasis. After the Introduction of complementary feeding, frequent bowel movements appear with large amounts of pale, oily, foul-smelling stools; the Liver enlarges, leading to cirrhosis, hypotrophy, and cachexia. Without proper treatment, patients die before the age of 10–12 years. Children with cystic fibrosis are intellectually well-developed. With consistent and appropriate treatment, patients can live up to 40 years. Elevated concentrations of sodium and chloride in sweat, Nails, and Hair hold specific diagnostic value ("salty child", "bitter tears"). In children aged 3–6 years, duodenal contents show decreased activity of lipase, diastase, and Trypsin. DNA diagnostics and prenatal testing are available. AR inheritance pattern. Treatment: dietary therapy (high-calorie, high-protein, salty, low-fat diet); enzyme therapy (Creon, Wobenzym, pancreatin, and similar products), inhalations with mucolytics, vibrational massage to facilitate mucus clearance, and anabolic Steroids. During infectious complications, antibiotic therapy is used as a preventive measure. Nosocomial infections are particularly dangerous for cystic fibrosis patients; therefore, isolated rooms (boxes) are required, and outpatient treatment combined with qualified home care, provided all physician requirements are met, is preferred.