hereditary disease

1. MONOGENIC
DISEASES

2. Hereditary diseases
of amino acid
metabolism

3. Phenylketonuria

4. • In patients, the conversion of the amino
acid phenylalanine to tyrosine is impaired
due to a sharp decrease in the activity of
the enzyme phenylalanine hydroxylase. As
a result, the content of phenylalanine in the
blood and urine of patients increases
significantly. Further, phenylalanine is
converted to phenylpyruvic acid, which is
a neurotropic poison and disrupts the
formation of the myelin sheath around the
axons of the central nervous system.

5. • Phenylketonuria occurs on an average
global scale with a frequency of 1 per 1000
newborns.Locus (phenylhydroxylase) is
located in the long arm of the 12th
chromosome. Molecular genetic diagnosis
and detection of heterozygous carriage are
currently possible.The disease is inherited
in an autosomal recessive manner. Several
forms of phenylketonuria are known,
which differ in the severity of the course of
the disease. This is due to the presence of 4
alleles of the gene and their combinations.

6. A child with phenylketonuria is born healthy,
but in the first weeks, due to the intake of
phenylalanine in the body with mother's milk,
hyperexcitability,
convulsive syndrome,
a tendency to dermatitis develop,
urine and sweat of patients have a characteristic
"mouse" smell, and subsequently, without
treatment, psychomotor delay occurs.
development and oligophrenia.

8. Most patients
are blondes
with fair skin
and blue eyes,
which is
determined by
insufficient
synthesis of
melanin
pigment.

9. Diagnostics
• Produced by a semi-quantitative test or quantitative
determination of phenylalanine in the blood.
• In untreated cases, it is possible to identify the
breakdown products of phenylalanine
(phenylketones) in the urine (not earlier than 10-12
days of a child's life).
• It is also possible to determine the activity of the
enzyme phenylalanine hydroxylase in a liver biopsy
and search for mutations in the phenylalanine
hydroxylase gene.

10. Treatment and prevention
• With timely diagnosis, pathological changes can be
completely avoided if, from birth to puberty, the
intake of phenylalanine with food is limited..
• Late initiation of treatment, although it gives a
certain effect, does not eliminate the previously
developed irreversible changes in brain tissue.

11. Treatment and prevention
• At the birth of a child in maternity
hospitals for 3-4 days, a blood test is
taken and neonatal screening is
performed to detect congenital metabolic
diseases. At this stage, detection of
phenylketonuria is possible, and, as a
result, an early start of treatment is
possible to prevent irreversible
consequences.

12. Treatment and prevention
• The treatment is carried out in the form of a strict
diet from the discovery of the disease at least until
puberty, many authors are of the opinion that a
lifelong diet is necessary.The diet excludes meat,
fish, dairy products and other products containing
animal and, in part, vegetable protein.Protein
deficiency is replenished with amino acid mixtures
without phenylalanine. Breastfeeding of children
with phenylketonuria is possible and can be
successful with some restrictions.

13. • Some (mild) forms of the disease respond to
treatment with a cofactor (tetrahydrobiopterin) of
the affected enzyme (phenylalanine hydroxylase).
• New approaches to the treatment of phenylketonuria
are being developed - the use of replacement therapy
with phenylalanine lyase (PAL), a plant enzyme that
converts phenylalanine into harmless metabolites,
and gene therapy based on the introduction of a viral
vector containing the phenylalanine hydroxylase
gene into the body. These methods have not yet left
the walls of laboratories. Atypical forms are not
amenable to diet therapy and are treated only with
the introduction of tetrahydrobiopterin preparations
or its synthetic analogues (sapropterin).

14. Hereditary
connective tissue
diseases

15. Marfan syndrome

16. Marfan syndrome
autosomal dominant disease from the
group of hereditary connective tissue
pathologies.
The syndrome is caused by mutations in
the genes encoding fibrillin-1
glycoprotein synthesis and is
pleiotropic.
The disease is characterized by varying
penetrance and expressivity.

17. • The cause of the disease is a
mutation in the gene responsible
for the synthesis of the
connective tissue fiber protein
fibrillin. Blocking its synthesis
leads to increased extensibility of
the connective tissue.

19. In classic cases,
individuals with
Marfan syndrome are
tall
(dolichostenomelia),
have elongated limbs,
extended fingers
(arachnodactyly) and
underdevelopment of
adipose tissue.

20. Arachnodactyly

21. In addition to the
characteristic changes
in the organs of the
musculoskeletal
system, there is a
pathology in the
organs of vision and
the cardiovascular
system, which in the
classical versions
constitutes the Marfan
triad.

22. wrist test

23. thumb test

24. Patients with
Marfan's syndrome
are distinguished by
high growth, long
spider-like fingers,
chest deformity
(funnel-shaped,
keeled, flattened),
flat feet.

25. Often there is a deterioration in vision,
a change in the shape and size of the
lens, significant myopia up to retinal
detachment, heterochromia (different
staining of the iris); subluxation of the
lens, cataract, strabismus.
• In addition to the above,
Marfan syndrome is
characterized by congenital
heart defects, aortic expansion
with the development of an
aneurysm.

26. • Treatment is mainly
symptomatic. Massage,
physiotherapy exercises, and in
some cases surgery have a
positive effect. Early diagnosis
of the disease is of great
importance.

27. Cystic fibrosis

28. • Cystic fibrosis is a
systemic hereditary
disease caused by a
mutation in the cystic
fibrosis transmembrane
regulator gene and
characterized by damage
to the external secretion
glands, severe disorders
of the respiratory and
gastrointestinal tract.

29. The pathological gene is localized in the middle
of the long arm of the 7th chromosome. Cystic
fibrosis is inherited in an autosomal recessive
manner.

30. There are the following clinical forms of cystic
fibrosis:
• predominantly pulmonary form (respiratory,
bronchopulmonary);
• predominantly intestinal form;
• mixed form with simultaneous damage to the
gastrointestinal tract and respiratory organs;
• meconium ileus;atypical and erased forms
(edematous-anemic, cirrhotic, etc.).

31. • Pathological
changes in the
lungs are
characterized by
signs of chronic
bronchitis with the
development of
bronchiectasis and
diffuse
pneumosclerosis..

32. In the lumen of the
bronchi there is a viscous
content of a mucopurulent
nature. A frequent finding
are atelectasis and areas of
emphysema.

33. • In many patients, the
course of the pathological
process in the lungs is
complicated by the
layering of a bacterial
infection (pathogenic
Staphylococcus aureus,
Haemophilus influenzae
and Pseudomonas
aeruginosa) and the
formation of destruction.

34. • Diffuse fibrosis,
thickening of
interlobular
connective tissue
layers, cystic
changes in small
and medium ducts
are detected in the
pancreas.

35. • In the liver, there is
focal or diffuse fatty
and protein
degeneration of liver
cells, bile stasis in the
interlobular bile
ducts,
lymphohistiocytic
infiltrates in the
interlobular layers,
fibrous transformation
and the development
of cirrhosis.

36. • With meconium ileus,
atrophy of the mucous
layer is expressed, the
lumen of the intestinal
mucous glands is
enlarged, filled with
eosinophilic secretion
masses, in some places
there is swelling of the
submucosal layer,
expansion of the
lymphatic slits.

37. • Often, cystic
fibrosis is
combined with
various
malformations of
the
gastrointestinal
tract.

38. Diagnosis of cystic fibrosis
• DNA
diagnostics is
the most
sensitive and
specific.
False results
are obtained
in 0.5-3% of
cases.

39. Cystic fibrosis treatment
symptomatic.correction of impaired pancreatic
function by using pancreatin or combined
preparations containing, along with pancreatin,
other intestinal enzymes and lipotropic substances
(polyzyme, panzinorm, mexase, etc.)
Treatment of pulmonary syndrome includes a set of
measures aimed at thinning sputum and removing
it from the bronchi. For this purpose, physical,
chemical and instrumental methods are used.
Mucolytic therapy is carried out daily throughout
the patient's life

40. • The criterion for the quality of
diagnosis and treatment of cystic
fibrosis is the average life
expectancy of patients. In European
countries, this figure reaches 40
years, in Canada and the USA - 48
years, and in Russia - 22-29 years.

41. Congenital hypothyroidism is a group of thyroid
diseases heterogeneous in etiology, manifesting
immediately after birth and characterized by
partial or complete loss of its function.

42. The thyroid gland is small in size and mass (in a
newborn it weighs no more than a gram, in a child of
5-10 years old - about 10 grams, in an adult - 30-35
g), like a shield covering the larynx, this gland
performs a very important function in the body. role.
It concentrates iodine from the blood plasma, absorbs
it, forming the hormone thyroxine, and ensures a
regular supply of this hormone into the blood.
Congenital hypothyroidism (CH) is a thyroid disorder
that occurs in 1 in 4,000 to 5,000 newborns. In girls, the
disease is detected 2–2.5 times more often than in boys.

43. The thyroid gland performs the following important
functions:Controls basal metabolism and body
temperature.Regulates the metabolism of proteins, fats and
carbohydrates.Regulates calcium metabolism.Participates in the
formation of human intelligence.
The thyroid gland produces three types of hormones:
triiodothyronine (T3), thyroxine (T4) and thyrocalcitonin. The first
two hormones (triiodothyronine and thyroxine) contain iodine. In
the human body, their role changes with age: during fetal
development and early childhood, these hormones contribute to the
development of bones (osteogenesis) and nervous tissue (especially
the brain). Thyrocalcitonin is a hormone that promotes the
accumulation of calcium in the body, which is especially important
in the process of growth of the skeleton and teeth.

44. Thyroxine is an energetic stimulator of all types of
metabolism, all biochemical processes occurring in
the body. It affects practically all organs, but
especially the heart and brain; without it normal
life is impossible. Thyroxine is vital for a growing
organism. With its deficiency, the growth of bones
in length is delayed, not only physical, but also
mental development is inhibited. That is why
congenital hypothyroidism, which develops in
utero, during the formation of the fetal endocrine
system, is especially dangerous.

45. In congenital hypothyroidism, various disorders of the
hypothalamus-pituitary-thyroid gland system are
observed. Therefore, the pathogenetic syndrome of
hypothyroidism is heterogeneous.
Etiology and pathogenesis of hypothyroidism.Depending on the level
of violation of the biosynthesis of thyroid hormones, there are:
- Primary (thyroid) hypothyroidism due to primary pathology of the
thyroid gland:a) as a result of a decrease in the amount of its
functionally active tissue;b) as a result of various defects in the
biosynthesis of thyroid hormones.
- Secondary (pituitary) hypothyroidism - as a result of a decrease or
loss of production of thyroid-stimulating hormone (TSH).

46. Symptoms of hypothyroidism in the first days of a child's life can
only be diagnosed in 5% of cases of congenital hypothyroidism.
Suspicions of the presence of this serious disease may arise from a
neonatologist if the newborn has the following symptoms of
hypothyroidism:Hyperbilirubinemia (jaundice) lasts more than a
weekbloated bellyumbilical hernia low husky voiceenlarged
posterior fontanel and thyroid glandhypotension (low muscle
tone).
By the 3rd month of life, the symptoms of hypothyroidism of the
thyroid gland are joined by: decreased appetite,difficulty
swallowing,flatulence,deviations from the norms of weight gain
and linear growth, pallor and dryness of the skin.At 9 months,
with congenital hypothyroidism, a delay in the psychomotor
development of the child becomes apparent.

47. Symptoms of hypothyroidism in
the first days of a child's life can
only be diagnosed in 5% of cases
of congenital hypothyroidism.
Suspicions of the presence of
this serious disease may arise
from a neonatologist if the
newborn has the following
symptoms of
hypothyroidism:Hyperbilirubin
emia (jaundice) lasts more than a
weekbloated bellyumbilical
hernia low husky voiceenlarged
posterior fontanel and thyroid
glandhypotension (low muscle
tone).

48. By the 3rd month of life, the symptoms of
hypothyroidism of the thyroid gland are joined
by:
decreased appetite,
difficulty swallowing,
flatulence,deviations from the norms of weight
gain and linear growth, pallor and dryness of
the skin.
At 9 months, with congenital
hypothyroidism, a delay in the psychomotor
development of the child becomes apparent.

50. The Apgar scale allows the diagnosis of congenital
hypothyroidism in newborns according to the following
indicators:
puffiness of the face - 2 points;
constipation - 2 points
the presence of an umbilical hernia - 2 points;
pallor of the skin - 1 point;
duration of jaundice exceeding 3 weeks - 1 point;
birth weight over 3,500 g - 1 point;
muscle weakness - 1 point;
the posterior fontanel is open - 1 point;
the tongue is enlarged - 1 point;
duration of pregnancy exceeding 40 weeks. - 1 point.

51. • Newborn screening test
Used to detect metabolic and genetic disorders in an
infant. A blood sample is taken with a prick in the
heel. The test allows you to detect and subsequently
take measures to prevent physical disabilities,
mental retardation and premature death of the child.
The time of the test is the first 24-72 hours of life.
Measurement of the level of TSH or thyroxine (T4).
The sample is taken on the second or third day of
life.
Thyroid study
Detects the presence of structural abnormalities of
the thyroid gland. This procedure will help in
differentiating if the reason for the examination is a
congenital absence or defect of an organ.

52. • The most severe complication is
hypothyroid coma. It develops, as a rule, in
a situation with hypothyroidism not
detected in a patient, as well as in the
absence of its treatment for a long time or
when the treatment is not effective enough.
• Symptoms of hypothyroid coma:
• coldness of the skin,
• its pallor, yellowness, dryness;rare
breathing;urinary retention;
• low blood pressure;bradycardia

53. The following drugs are used: Levothyroxine
sodium. "L-thyroxine". "Eutiroks". "Tiro-4". "L-
thyroxine-acry". "L-thyroxine-Farmak«
To improve metabolism in the brain: "Piracetam"
("Lucetam", "Nootropil"). "Aminalon"
("Ganevrin", "Encephalon", "Gammalon")
"Pyriditol" ("Encephabol", "pyritinol") "Mexidol"
"Cerebrolysin" "Tanakan".
The following antianemic drugs are prescribed:
iron preparations - Ferrum Lek, Ferroplex,
Aktiferrin, Totema, Hemofer); folic acid; B
vitamins.
Laxatives: Bisacodyl. "Lactulose". "Senade".
Treatment

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