Mitochondrial_Diseases_Flashcards
Where is most DNA found in the cell?
Most DNA is found in the cell nucleus, but a small amount of double-stranded DNA is present in the mitochondria.
What does mitochondrial DNA encode?
It encodes protein components of the respiratory chain and some special types of RNA.
What are the characteristics of mitochondrial inheritance?
Inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote. None of the children of an affected male will inherit the disease. All of the children of an affected female will inherit the disease. Generally, encode rare neurological diseases. Poor genotype:phenotype correlation due to heteroplasmy (different mitochondrial populations within a tissue or cell).
What does muscle biopsy classically show in mitochondrial diseases?
Muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria.
What are examples of mitochondrial diseases?
Leber’s optic atrophy, MELAS syndrome (mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes), MERRF syndrome (myoclonus epilepsy with ragged-red fibres), Kearns-Sayre syndrome (onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa, ptosis), sensorineural hearing loss.
What are the symptoms of Leber’s optic atrophy?
Symptoms typically develop at around the age of 30 years: central scotoma → loss of colour vision → rapid onset of significant visual impairment.
What are the symptoms of MELAS syndrome?
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes.
What are the symptoms of MERRF syndrome?
Myoclonus epilepsy with ragged-red fibres.
What are the symptoms of Kearns-Sayre syndrome?
Onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa, ptosis.
summarise
Mitochondrial diseases
Whilst most DNA is found in the cell nucleus, a small amount of double-stranded DNA is present in the mitochondria. It encodes protein components of the respiratory chain and some special types of RNA
Mitochondrial inheritance has the following characteristics:
inheritance is only via the maternal line as the sperm contributes no cytoplasm to the zygote
none of the children of an affected male will inherit the disease
all of the children of an affected female will inherit the disease
generally, encode rare neurological diseases
poor genotype:phenotype correlation - within a tissue or cell there can be different mitochondrial populations - this is known as heteroplasmy
Histology
muscle biopsy classically shows ‘red, ragged fibres’ due to increased number of mitochondria
Examples include:
Leber’s optic atrophy
symptoms typically develop at around the age of 30 years
central scotoma → loss of colour vision → rapid onset of significant visual impairment
MELAS syndrome: mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes
MERRF syndrome: myoclonus epilepsy with ragged-red fibres
Kearns-Sayre syndrome: onset in patients < 20 years old, external ophthalmoplegia, retinitis pigmentosa. Ptosis may be seen
sensorineural hearing loss
A 27-year-old man is referred for genetic counselling following a diagnosis of Leber’s optic atrophy. The patient wishes to know the likelihood that his future children will inherit the condition.
The genetic counsellor explains that Leber’s optic atrophy is caused by a mutation in his mitochondrial DNA.
What is the probability that the patient will pass on this condition to his future children?
0%
25%
50%
75%
100%
0%
For a man with mitochondrial disease, none of his children will inherit the condition
0% is the correct answer. Mitochondrial diseases are inherited from mother to child only, mitochondria from the ovum and not the sperm are present in the zygote at fertilisation. As the patient is male, there is a 0% probability that any of his future children will inherit his mitochondrial disease.
25%, 50%, 75%, and 100% are incorrect answers, as there is a 0% probability of a man with a mitochondrial disease, such as Leber’s optic atrophy, passing on his condition to his offspring. Conversely, if the patient were female, 100% of her children would develop Leber’s optic atrophy, as only maternal mitochondrial is passed onto offspring.
A 43-year-old male with a history of Leber’s optic atrophy, presents to his GP. He and his wife have decided they would like to have children and he wants to know what chance his offspring have of inheriting his condition. He remembers his geneticist telling him ‘something about mitochondria’ but he can’t recall any more details about the inheritance pattern.
Assuming his wife does not carry the same gene defect, what is the probability that a child of his will inherit the condition?
0%
25%
50%
75%
100%
0%
For a man with mitochondrial disease, none of his children will inherit the condition
Leber’s optic atrophy is a mitochondrially inherited disease that can lead to a loss of vision.
Mitochondrial DNA is always passed down the maternal line. Mitochondrial genetic diseases are never transmitted from males to their offspring. Therefore the only answer that can be correct is ‘0%’.
Other examples of mitochondrial disorders include leigh syndrome, mitochondrial diabetes, MELAS syndrome, and MERFF syndrome.
