Hereditary diseases and their effect on health

Hereditary diseases and their effect on health

I. Fundamentals of genetics and heredity

Hereditary diseases, or genetic disorders, occur as a result of changes or mutations in the human genetic material, DNA (deoxyribonucleic acid). Understanding the foundations of genetics and heredity is necessary for the realization of the nature of these diseases, ways to transfer them and their effects on health.

A. DNA, genes and chromosomes

DNA is “instructions” for the construction and functioning of the body. It consists of four nucleotide bases: adenina (a), tymin (t), cytosine (C) and guanine (G). The sequence of these bases determines the genetic code.

• Genes: DNA section containing information necessary for the synthesis of a certain protein or functional RNA. Proteins perform a wide range of functions in the body, from catalysis of biochemical reactions to the formation of structural components of cells.

• Chromosomes: DNA is organized in structures called chromosomes. A person has 23 pairs of chromosomes (46 in total), half of which are inherited from the mother, and half of his father. One pair – sexual chromosomes (XX in women, XY in men).

B. Mutations and their types

Mutations are changes in the DNA sequence. They can occur spontaneously in the process of DNA replication or be caused by external factors (for example, radiation, chemicals). Mutations can be:

• Crack mutations: Modification of one nucleotide in the genes.

  • Replacements: One nucleotide is replaced by another (for example, A on G).
    • Missens-Mutacii: Replacing nucleotide leads to a change in the encoded amino acid in the protein. This can affect the protein function.
    • Nonsense: Replacing nucleotide leads to the formation of a stop codon, which prematurely stops the synthesis of protein. Usually leads to non -functional protein.
    • Silent mutations: The replacement of nucleotide does not lead to a change in the amino acid (due to the degeneration of the genetic code).
  • Inserts and deletions: Adding or removal of one or more nucleotides in the gene. This can lead to a shift in the reading frame, which completely changes the sequence of amino acids in the protein.

• Chromosomal mutations: Changes in the structure or quantity of chromosomes.

  • Deletions: Loss of the chromosome site.
  • Duplications: Doubling the site of the chromosome.
  • Inversions: The section of the chromosome is turned 180 degrees.
  • Translocations: The section of the chromosome is transferred to another chromosome.
  • ANEULOIDIDID: Changing the number of chromosomes (for example, trisomy – the presence of three copies of the chromosome instead of two).

C. Types of inheritance

The method of transmitting a hereditary disease from parents to offspring depends on the type of gene in which a mutation (autosomal or sexual) occurred and on whether the mutation is dominant or recessive.

• Autosomal dominant inheritance: The disease manifests itself if a person has at least one copy of the mutant gene on one of the autosomes (not sex chromosomes). The probability of transmitting a mutant gene to the offspring is 50%if one of the parents is a carrier of a mutation. Examples: Huntington disease, neurofibromatosis.

• Autosomal recessive inheritance: The disease manifests itself only if a person has two copies of a mutant gene (one from each parent) on one of the autosomes. Parents with only one copy of the mutant gene are carriers and do not show signs of the disease. The probability of the birth of a sick child in two media is 25%. Examples: cystic fibrosis, phenylketonuria, sickle cell anemia.

• X-linked dominant inheritance: The mutant gene is located on the X chromosome, and the disease manifests itself even in the presence of one copy of the mutant gene. Women with one mutant X-chromosome will show a disease, and men with a mutant X-chromosome will also be sick (since they have only one X chromosome). Examples: Retta syndrome (in most cases is flying for boys), vitamin-D-resistant rickets.

• X-linked recessive inheritance: The mutant gene is located on the X chromosome, and the disease manifests itself in men who have only one X chromosome with a mutation. Women with one mutant X-chromosome are usually carriers and do not show signs of the disease, but can convey the mutation to their children. In order for a woman to get sick, she needs to inherit two mutant x chromosomes (one from each parent). Examples: hemophilia, Dyushenna dystrophy, color blindness.

• Y-linked inheritance: The mutant gene is located on the Y chromosome, and the disease is transmitted only from father to son.

• Mitochondrial inheritance: Mitochondria (organelles in cells responsible for energy production) have their own DNA. Mutations in mitochondrial DNA are transmitted only from mother to children, since spermatozoa practically do not contain mitochondria. Examples: mitochondrial myopathy.

• Multifactorial inheritance: Many diseases are the result of the interaction of genetic factors and environmental factors. They do not follow simple inheritance models. Examples: diabetes, cardiovascular diseases, some types of cancer, crevice of the lips and sky.

II. The most common hereditary diseases

There are a huge number of hereditary diseases, each of which is characterized by its own characteristics and impact on health. Consider some of the most common and clinically significant.

A. Cykovyskidosis (cystic fibrosis)

• Genetics: Autosomal recessive disease caused by mutations in the CFTR gene (Cystic Fibrosis Transmebrane Conductance Regulator), which encodes protein that regulates the transport of chlorides through cell membranes.
• Impact on health: Mutations in the CFTR gene lead to the formation of thick and viscous mucus, which affects the lungs, pancreas, intestines and other organs.
• Symptoms: Chronic coughing, recurring pulmonary infections, difficulty breathing, poor absorption of food, diarrhea, growth retardation, infertility in men.
• Treatment: Symptomatic treatment, including chest physiotherapy, antibiotics, mucolytic, enzyme drugs, diet therapy, as well as drugs that correct the CFTR protein function (CFTR modulators).

B. Phenylketonuria (FCU)

• Genetics: Autosomal recessive disease caused by mutations in the Pahnylalanine Hydroxylase gene, which encodes the enzyme phenylaneineryxylase, which is necessary for the transformation of phenylalanine into tyrosine.
• Impact on health: The deficiency of phenylaneineinexylasis leads to the accumulation of phenylalanine in the blood and tissues, which has a toxic effect on the brain.
• Symptoms: If FCU is not treated, this can lead to mental retardation, convulsions, behavioral problems, developmental delay, eczema, a “mouse” smell from the body.
• Treatment: A special diet with a restriction of phenylalanin, starting from birth. Early detection and treatment of FCU allows you to prevent irreversible brain damage.

C. sickle -cell anemia

• Genetics: Autosomal recessive disease caused by mutations in the HBB gene (Hemoglobin Subunit Beta), which encodes the beta-globine chain of hemoglobin.
• Impact on health: Mutations in the HBB gene lead to the formation of abnormal hemoglobin, which causes erythrocyte deformation in a sickle form. Sick -shaped cells pass less flexible and pass through small blood vessels, which leads to blockage of blood vessels and impaired blood supply to organs and tissues.
• Symptoms: Chronic anemia, pain in bones and joints (vaso -cluster crises), frequent infections, damage to organs (lungs, kidneys, heart, brain), growth and development retention.
• Treatment: Anesthetic drugs, antibiotics, blood transfusion, hydroxymochevin (a drug that increases the level of fetal hemoglobin), bone marrow transplantation.

D. Hemophilia

• Genetics: X-linked recessive disease. There are two main types of hemophilia:
  • Hemophilia A: It is caused by mutations in the F8 (Coagulation factor VIII), which encodes the coagulation factor VIII.
  • Hemophilia B: It is caused by mutations in the F9 gene (Coagulation factor IX), which encodes the coagulation factor IX.
• Impact on health: The deficiency of coagulation factors VIII or IX leads to a violation of the blood coagulation process and increased bleeding.
• Symptoms: Long bleeding after injuries or operations, spontaneous bleeding in the joints, muscles and internal organs.
• Treatment: Replacement therapy with coagulation factors VIII or IX, preventive administration of coagulation factors to prevent bleeding.

E. Huntington’s disease (Khorea Huntington)

• Genetics: Autosomalum-dominant disease caused by the expansion of trinucleotide repetitions of CAG in the HTT (HuntingTin) gene, which encodes the Hunting protein.
• Impact on health: CAG expansion leads to the formation of an abnormal HuntingTin protein, which damages neurons in the brain, especially in basal ganglias.
• Symptoms: Involuntary movements (chorea), impaired coordination, mental disorders (depression, irritability, psychosis), cognitive disorders (decrease in memory, attention, thinking). Symptoms usually appear in adulthood (30-50 years).
• Treatment: Symptomatic treatment to relieve motor and mental symptoms. There is no treatment that could stop the progression of the disease.

F. Muscle Distrophy Dyushenna (MDD)

• Genetics: X-linked recessive disease caused by mutations in the DMD (Dystrophin) gene, which encodes the dystrophin protein necessary to maintain the structure and function of muscle fibers.
• Impact on health: Deficiency of dystrophine leads to progressive muscle weakness and atrophy.
• Symptoms: Muscle weakness, starting from the feet, difficult movements, frequent falls, hypertrophy of the calf muscles (pseudohypertrophy), curvature of the spine (scoliosis), cardiomyopathy, respiratory failure. Symptoms usually appear in early childhood.
• Treatment: Symptomatic treatment, including physiotherapy, orthosis, corticosteroids (to slow down the progression of muscle weakness), respiratory support. There is no treatment that could cure MDD. Gene therapy is under development.

G. Trisomy 21 (Down Syndrome)

• Genetics: Chromosomal disease caused by the presence of an additional copy of the 21st chromosome (trisomy).
• Impact on health: Trisomy 21 leads to multiple disorders of the development and functioning of the body.
• Symptoms: Characteristic facial features (flat face, oblique eyes, short neck), mental retardation, heart defects, anomalies of the gastrointestinal tract, increased risk of leukemia, reduced immunity.
• Treatment: Symptomatic treatment aimed at correcting malformations, treatment of related diseases, development of skills and adaptation to life.

H. Spinal muscle atrophy (SMA)

• Genetics: Autosomal recessive disease caused by mutations or deeds in the SMN1 gene (Survival Motor Neuron 1), which encodes the SMN protein necessary for the survival of motor neurons (nerve cells that control muscles).
• Impact on health: SMN protein deficiency leads to the death of motor neurons, which causes progressive muscle weakness and atrophy.
• Symptoms: Muscle weakness, starting from the feet and spreading to other muscles, difficulty breathing, problems with swallowing, scoliosis. The severity of the symptoms depends on the type of SM (type 1 is the most severe).
• Treatment: Previously, treatment is crucial. There are drugs that increase the level of SMN protein (nusinersen, risads) and genetic therapy (A Semnogen Abeparuvets), aimed at replacing the defective gene SMN1.

I. Neurofibromatosis (NF)

• Genetics: There are two main types of neurofibromatosis:
  • Type 1 neurofibromatosis (NF1): Autosomalum-dominant disease caused by mutations in the NF1 gene (neurofibromin 1), which encodes a neurofibromin protein that regulates cell growth.
  • Type 2 neurofibromatosis (NF2): Autosomalum-dominant disease caused by mutations in the NF2 gene (Neurofibromin 2), which encodes Merlin protein (Schannanomin), which regulates cell growth and cell adhesion.
• Impact on health: Mutations in the genes of NF1 or NF2 lead to the formation of tumors (neurofiber, Swann) in the nervous system, skin and other organs.
• Symptoms:
  • NF1: Spots of the colors of “coffee with milk” on the skin, neurofibromes (benign tumors from Schwann cells), lichen nodules (pigment spots on the iris of the eye), bone anomalies, and learning problems.
  • NF2: Schannami auditory nerve (tumors that affect hearing and equilibrium), meningiomas (tumors of the brain shells), ependymum (spinal cord tumors), cataracts.
• Treatment: Surgical removal of tumors, radiation therapy, chemotherapy, symptomatic treatment.

J. Galacto -Zemoi

• Genetics: Autosomal recessive disease caused by mutations in genes encoding enzymes necessary for the metabolism of galactose. The most common form is the classic galactosemia caused by mutations in the GALT (Galactose-1-Phosphate Uridyltransferase).
• Impact on health: The deficiency of enzymes leads to the accumulation of galactose and its metabolites in the blood and tissues, which has a toxic effect on the liver, brain and kidneys.
• Symptoms: Vomiting, diarrhea, jaundice, hepatomegaly (enlargement of the liver), cataracts, developmental delay, mental retardation, convulsions.
• Treatment: A strict diet with the exception of galactose, starting from birth. Early detection and treatment of galactosemia allows you to prevent serious complications.

III. Diagnosis of hereditary diseases

Early and accurate diagnosis of hereditary diseases is crucial for the timely start of treatment and reducing the risk of complications. There are various diagnostic methods that are used at different stages of life.

A. Prenatal diagnosis

Prenatal diagnosis allows you to identify genetic diseases in the fetus during pregnancy.

• Screening of the first trimester: Combined screening, including an ultrasound examination (measurement of the thickness of the collar space) and a biochemical blood test of the mother (determination of the level of PAPP-A and free beta-HCG). Allows you to evaluate the risk of chromosome anomalies (for example, Down syndrome).
• Screening of the second trimester (triple or quadruple test): Biochemical analysis of the blood of the mother (determination of the level of AFP, hCG, estriol and inhibin A). Allows you to evaluate the risk of chromosomal abnormalities and defects in the nervous tube.
• Non -invasive prenatal test (NIPT): Analysis of fetal DNA in the blood of the mother. Allows you to identify chromosomal abnormalities (for example, Down syndrome, Edwards syndrome, Patau syndrome) with high accuracy.
• Amniocentez: Invasive procedure in which an example of amniotic fluid surrounding the fetus is taken. The amniotic fluid contains fetal cells that can be used for genetic analysis.
• Chorion Biopsy: Invasive procedure in which a sample of the chorion villi is taken (fabric, which will subsequently become a placenta). Chorion villi contain fetal cells that can be used for genetic analysis.
• Cordocentesis: Invasive procedure in which a blood sample is taken from the fetal umbilical cord. It is used less often than amniocentesis and choriona biopsy.

B. Screening of newborns

Screening of newborns is a program of mass examination of newborns for certain hereditary diseases. Early identification of these diseases allows you to start treatment in the early days of or week of life, which can prevent serious complications.

• Blood fence from the heel: A small amount of blood is taken from the heel of the newborn and applied to special filter paper.
• Blood test: Blood is analyzed for certain metabolites, which may indicate the presence of a hereditary disease.
• List of diseases: The list of diseases included in the newborns screening program varies depending on the country and the region. Typically, it includes phenylketonuria, cystic fibrosis, hypothyroidism, galactosemia, adrenogenital syndrome and others.

C. Genetic testing

Genetic testing allows you to identify mutations in genes that can cause hereditary diseases.

• Cariotipirani: Analysis of chromosomes to detect chromosomal abnormalities (for example, trisomy, deletion, translocation).
• Fluorescence hybridization in situ (fish): The method used to identify specific DNA sections on chromosomes.
• Polymerase chain reaction (PCR): A method used for amplification (multiplication) of a certain DNA section.
• DNA sequencing: Determination of the sequence of nucleotides in DNA. Allows you to identify accurate mutations, inserts, deletions and other changes in DNA.
  • Senger sequencing: The traditional method of DNA sequencing.
  • New generation sequencing (NGS): The high -performance method of DNA sequencing, which allows simultaneously securing many DNA sections or whole genomes.
• Analysis of microuines: The method used to identify delections and duplications in DNA.

D. Consultation of genetics

Consultation of genetics is recommended for families in which there are cases of hereditary diseases, or pairs planning pregnancy and having an increased risk of a child with a hereditary disease.

• Risk assessment: The geneticist evaluates the risk of a child’s birth with a hereditary disease based on a family history, ethnicity and other factors.
• Discussion of diagnostic options: The geneticist discusses various options for prenatal and postnatal diagnostics, as well as their advantages and risks.
• Interpretation of test results: The geneticist interprets the results of genetic tests and explains their significance for the family.
• Recommendations for treatment and prevention: The geneticist gives recommendations for the treatment and prevention of hereditary diseases.
• Psychological support: The geneticist provides psychological support to families faced with hereditary diseases.

IV. Treatment and prevention of hereditary diseases

Treatment and prevention of hereditary diseases is aimed at alleviating symptoms, preventing complications and improving the quality of life of patients.

A. Drug treatment

Drug treatment can be directed at:

• Replacing scarce substances: For example, enzyme preparations for cystic fibrosis, blood coagulation factors for hemophilia, thyroxine for hypothyroidism.
• Reducing the level of toxic substances: For example, a diet with a restriction of phenylalanine for phenylketonuria, iron heels with hemochromatosis.
• Relief of symptoms: For example, painkillers for sickle cell anemia, broncholitics for cystic fibrosis.
• Treatment of concomitant diseases: For example, antibiotics for infections in patients with cystic fibrosis, cardiac drugs for cardiomyopathy in patients with Dyushenna muscle dystrophy.

B. Surgical treatment

Surgical treatment may be necessary for the correction of malformations, removal of tumors or conducting organs.

• Correction of heart defects: With Down syndrome, heart defects are often found, which require surgical correction.
• Removing neurofibrom: With neurofibromatosis, tumors can squeeze nerves or other organs, which requires surgical removal.
• Bone marrow transplantation: It can be used to treat sickle cell anemia, talassemia and some other hereditary diseases.
• Lung transplantation: It may be necessary for patients with cystic fibrosis who developed severe respiratory failure.
• Transplantation Baked: It may be necessary for patients with galacto -people who have developed liver failure.

C. Physiotherapy and rehabilitation

Physiotherapy and rehabilitation play an important role in maintaining muscle function, improve mobility and prevent complications in patients with hereditary diseases that affect the nervous system and muscles.

• Exercises for strengthening muscles: Help maintain muscle strength and improve mobility.
• Exercises for stretching: Help prevent contractures and improve flexibility.
• Respiratory physiotherapy: Helps cleanse the respiratory tract of mucus and improve the function of the lungs.
• Orthes and auxiliary means: They can help maintain the correct position of the body, improve mobility and prevent deformations.

D. Diet therapy

Diet therapy plays an important role in the treatment of hereditary metabolic diseases.

• Restriction of certain products: For example, a diet with a restriction of phenylalanine with phenylketonuria, a diet with the exception of galactose in galactocurium.
• Adding certain substances: For example, enzyme preparations for cystic fibrosis, vitamin and mineral additives for various hereditary diseases.

E. Gene therapy

Gene therapy is a promising method of treating hereditary diseases, which is aimed at correcting a genetic defect.

• Introduction of a normal copy of the gene: A normal copy of the genet is entered into the patient’s cells to compensate for a defective copy.
• Genes editing: Special gene editing tools are used (for example, CRISPR-CAS9) to correct the defective gene in the patient’s cells.
• Inhibiting the expression of a defective gene: Special molecules are used to block the expression of a defective gene.

Gene therapy is under development and is still available for the treatment of a limited number of hereditary diseases.

F. Prenatal and preimplanting genetic diagnostics (PGD)

Prenatal diagnosis allows you to identify genetic diseases in the fetus during pregnancy. Preimplantation genetic diagnostics (PGD) is a method that is used for extorporeproof fertilization (ECO). The embryos obtained as a result of IVF are tested for the presence of genetic diseases, and only healthy embryos are transferred to the uterus.

G. Preventive measures

• Genetic counseling: Family couples planning pregnancy, especially if the family has cases of hereditary diseases, should turn to genetics to assess the risk of a child with a hereditary disease and discuss diagnostic and prevention options.
• Screening of carriage: Screening of carriage allows you to identify people who are carriers of mutations that cause autosomal recessive or X-combined recessive diseases. This can be useful for couples planning pregnancy and wanting to evaluate the risk of a child with a hereditary disease.
• Vaccination: Some hereditary diseases, such as Viscott-Oldrich syndrome, increase the risk of infections. Vaccination helps to protect these patients from infectious diseases.
• Healthy lifestyle: A healthy lifestyle, including a balanced nutrition, regular physical exercises and the rejection of smoking and alcohol, can help improve health and reduce the risk of complications in patients with hereditary diseases.

V. Psychological and social aspects of hereditary diseases

Hereditary diseases have a significant impact not only on physical health, but also on the psychological state of patients and their families.

A. Psychological impact

• Diagnosis: The diagnosis of a hereditary disease can be a shock for the patient and his family. This can lead to a feeling of fear, anxiety, depression, guilt and anger.
• Chronic disease: Life with a chronic hereditary disease can be complex and require constant care and treatment. This can lead to a sense of fatigue, frustration and social insulation.
• Uncertainty: The uncertainty regarding the future course of the disease and the risk of transferring it to the offspring may be a source of constant stress.
• Stigmatation: Patients with hereditary diseases may face stigmatization and discrimination in society.

B. Social aspects

• Family relations: Hereditary diseases can influence family relationships. This can lead to conflicts, misunderstanding and increased load on family members who care for the patient.
• Financial costs: Treatment and care of patients with hereditary diseases can be expensive. This can create financial difficulties for the family.
• Education and work: Hereditary diseases can limit the possibilities of patients in education and employment.
• Social support: It is important that patients and their families receive social support from friends, relatives, medical workers and patient organizations.

C. Psychological help

• Psychologist consultations: Consultations of a psychologist can help patients and their families cope with emotional difficulties associated with a hereditary disease.
• Support groups: Support groups allow patients and their families to communicate with other people faced with similar problems.
• Psychotherapy: Psychotherapy can help patients and their families change the negative thoughts and behavior associated with a hereditary disease.

VI. The future treatment of hereditary diseases

The future treatment of hereditary diseases looks promising. Studies in the field of genetic therapy, editing genes, the development of new drugs and improvement of diagnostic methods are ongoing.

A. Gene therapy and editing genes

General therapy and editing of genes are promising methods of treating hereditary diseases that can allow to correct the genetic defect and cure the disease.

B. New drugs

The development of new drugs that can relieve symptoms, prevent complications and improve the quality of life of patients with hereditary diseases.

C. Improvement of diagnostic methods

New diagnostic methods are being developed, which allow you to identify hereditary diseases in the early stages, which makes it possible to start treatment earlier and reduce the risk of complications.

D. Personalized medicine

Personalized medicine is an approach to treatment, which takes into account the individual genetic characteristics of each patient. This allows you to choose the most effective and safe treatment for each patient.

E. Ethical questions

The development of new technologies in the treatment of hereditary diseases poses ethical issues that must be taken into account.

• Accessibility of treatment: It is important that new methods of treating hereditary diseases are available to all patients, regardless of their financial situation.
• Safety: It is necessary to make sure that new methods of treating hereditary diseases are safe and do not cause serious side effects.
• Justice: It is necessary to ensure a fair distribution of resources aimed at the treatment of hereditary diseases.

Understanding of hereditary diseases and their impact on health is an important step towards improving the life of patients and their families. Thanks to progress in the field of genetics, diagnosis and treatment, the future of patients with hereditary diseases is becoming increasingly encouraging.