KHARKIV NATIONAL MEDICAL UNIVERSITY

MEDICAL GENETICS
CONTENTS MODULE 6.
MITOCHONDRIAL DISEASES Guidelines for students ??????? ????????
????????? ?????? 6.
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??????????? ???????????? ???????? ??????????? MEDICAL GENETICS
CONTENTS MODULE 6.
MITOCHONDRIAL DISEASES Guidelines for students ??????? ????????
????????? ?????? 6.
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?.?. ?????? ?edical genetics. ?ontents module 6. ?itochondrial diseases : Guidelines
for students / Cont. E.Y. Grechanina, Y.B. Grechanina, L.V. Molodan et al.
- Kharkiv : KhNMU, 2013. - 73 p.
Contens E.Y. Grechanina
Y.B. Grechanina
L.V. Molodan
E.P. Zdubskaya
E.V. Bugayova
A.I. Bezrodnaya
L.A. Turova The largest number of mitochondrias contains enerhotrophy organs - brain,
heart, liver, skeletal muscle, kidney, endocrine and respiratory systems,
so first of all, suffer these organs and systems together or alternately.
Mitochondrial disease is genetically heterogeneous and clinically
polymorphic. Early onset results in a heavier flow, given that the early
manifestation of mitochondrial disease coincides with the abnormal
accumulation of mutant DNA and proceeds progressively quickly.
Depending on which organ affected, patients may present complaints of
violations of motor control, muscle weakness and muscle pain, as localized
and diffuse, gastrointestinal disturbances (vomiting, diarrhea with signs
of exocrine pancreatic insufficiency) and swallowing difficulties, voice
hoarseness, linked with weakness vocal ligaments, growth retardation, heart
disease in a large spread of mitral valve prolapse to the different
versions of cardiomyopathies, the formation of diabetes, liver disease,
which contain hepatomegaly or different versions of idiopathic autoimmune
hepatitis In these patients, may cause seizures or epi-equivalents,
followed by the formation of epilepsy, problems with hearing (sensorineural
deafness or hearing), visual (often changes associated with the optic
nerve, including retinitis pigmentosa), respiratory disorders (worth Memory
'mind that the primary manifestation of distress - respiratory syndrome,
which can lead to sudden death of a child or adult is repeated episodes of
apnea in children, snoring and periodic cyanosis nasolabial triangle under
emotional stress), lactic acidosis, which untreated can lead to acidotic
coma common developmental disorders and susceptibility to frequent
respiratory diseases (different types of immune disorders).
The most common symptoms include the following mitohondriopaty syptomo -
complex:
. myopathy, polymyositis;
. ophthalmopathy;
. encephalopathy;
. hepatomegaly;
. cardiomegaly;
. epilepsy;
. diabetes.
Most patients suffering from mitochondrial diseases impose the following
complaints:
. muscle weakness, fatigue, syndrome "lifeless baby" syndrome, chronic
fatigue, exercise intolerance;
. headaches, episodes of loss of consciousness and convulsive seizures,
loss of previously acquired skills, dementia;
. acidotic vomiting, coma;
. skeleton disorders (dwarfism);
. blurred vision, blindness, ophthalmoplegia;
. hearing impairment;
. cardialgia, myalgia.
An examination of these patients exhibit the following changes:
. elevated levels of lactate dehydrogenase;
. elevated levels of alkaline phosphatase;
. elevated kreatinfosfokinazy;
. hypoglycemia;
. hematuria;
. increasing ESR;
. rhabdomyolysis (identifying the phenomenon of "ragged" red fibers RRF by
light microscopy of muscle biopsies);
. lactic acidosis. Classification of mitochondrial diseases by type of mutations in mtDNA
(classification Wallace, 1992): |Type of |Diseases |
|mutation| |
|s | |
|1. |- Neyrooftalmopatia of Leber (LHON); |
|misens |- Retinitis pigmentosa |
|mutation| |
|s | |
|2. |- Syndrome MERF (myoclonus-epilepsy |
|Mutation|syndrome, "ragged red fibers"; |
|s in the|- Syndrome MELAS (mitochondrial |
|genes of|entsefalomiopatia, lactic acidosis, |
|t-RNA |insult-like episodes) |
|3. |- external ophthalmopathy; |
|deletion|- Cairns-Sayre syndrome (KSS syndrome); |
|s or |- Pearson syndrome (refractory anemia |
|duplicat|sydero-Blast cells with vacuolization tive|
|ions of |brain and exocrine pancreatic |
|parts |dysfunction); |
|mtDNA |- Asymmetric ptosis; |
| |- Bilateral ptosis with oftalmoparez and |
| |weakness of the muscles of the lower |
| |extremities; |
| |- Dilatational cardiomyopathy; |
| |- NARP - syndrome (neuropathy, ataxia and |
| |retinitis pigmentosa) |
|4. |- lethal infantile respiratory failure; |
|mutation|- Syndrome of lactic acidosis. |
|s that | |
|reduce | |
|the | |
|number | |
|of | |
|copies | |
|of mtDNA| |
|5. |- Fumaric acydemiya; |
|mutation|- Glutaric acydemiya; |
|s in |- Lack of acyl-CoA dehydrogenase fatty |
|nuclear |acids with long respiratory chain; |
|DNA |- Lack of 3-hydroksiatsyl-CoA |
| |dehydrogenase fatty acids with long |
| |respiratory chain; |
| |- Lack of 3-hydroksiatsyl-CoA |
| |dehydrogenase fatty acids with an average |
| |respiratory chain; |
| |- Lack of 3-hydroksiatsyl-CoA |
| |dehydrogenase fatty acids with short |
| |respiratory chain; |
| |- Subacute necrotizing entsefalomiopatia |
| |of Leigh; |
| |- Progressive sclerosing poliodystrofia of|
| |Alpers; |
| |- Tryhopolidystrofia of Menkes. | The overall aim - to be able to recognize common signs of mitochondrial
genetic diseases, diagnostic criteria for individual nosological forms with
different types of inheritance.
The aim of education:
1. recognize the clinical manifestations of these mitochondrial diseases:
MELAS, MERRF, MNGIE, Kearns-Sayre, Leigh and others;
2. determine the need for additional examination of the patient, including
biochemical, instrumental and molecular-genetic, based on common features
of mitochondrial diseases.
The aims of the initial level of knowledge and skills:
1. determine the general issues of etiology, pathogenesis, genetics of
mitochondrial diseases, their classification;
2. identify individual nosological forms of mitochondrial disease on the
basis of somato-genetic examination, clinical and genealogical and
syndromologic analysis;
3. Data Interpretation basic laboratory and special methods of examination
(biochemical, instrumental, molecular genetic) mitochondrial diseases;
4. determine the methods of prevention and treatment (pathogenetic and
symptomatic) studied mitochondrial disease.
To determine whether the output level of your knowledge and skills
required, perform the following tasks. The correctness problem solving
check, comparing with the standard. Tasks for self and self-correction baseline skills. Task 1.
What are the most frequent symptoms characteristic of mitochondrial
disease?
A. Scoliosis, kyphosis, aortic aneurysm, dislocation hrustaliku,
arachnodactyly.
B. Glucose intolerance, cataracts, stool disorders, mental retardation.
C. Progressive myopathy, cardiomyopathy, impaired vision.
Task 2.
The child is vomiting, deterioration of the background of infectious
diseases, the smell of acetone mouth during seizures, progressive muscle
weakness. In phenotype delay stature, cranial-facial dyzmorfia.
Examinati