Mitochondrial Disorders Flashcards
What is the mnemonic of mitochondrial disorders?
LUMP
What are the mitochondrial diseases?
L = Leber’s optic atrophy (= LHON: Leber’s hereditary optic neuropathy)
Leigh syndrome
U = Usher’s syndrome
M = MELAS syndrome
MERRF syndrome
Mitochondrially inherited: Diabetes mellitus, and Deafness
P = Pearson syndrome
Progressive external ophthalmoplegia: Kearns-Sayre syndrome
Progressive neurodegenrative disease: NARP syndrome
Apart from nucleus, where else is the DNA located?
Mitochondria
Are Mitochondrial DNAs single stranded or double-stranded?
Double stranded
How does mitochondrial genes differ from nuclear genes?
- Mitochondrial genes have NO introns
- They encode some different amino acid codon
What are the functions of mitochondrial DNA?
To encode >>
- Respiratory chain enzyme subunits (protein components)
- Transfer RNAs (tRNAs)
Who can transmit the disease? father/mother?
Mother
(inheritence is only via maternal line)
Why is the inheritence of mitochondrial diseases only via maternal line?
because, mitochondria is present in cytoplasm
& sperm do NOT contribute any cytoplasm to the zygote
Type & Amount of genome in the cytoplasm of ovum (that is contributed to zygote)
Circular genome
16.5kilobase (kb)
What is heteroplasmy?
Within cells/tissues >>> mixed population of normal and abnormal mitochondria
Which type of genetic disorders does show heteroplasmy?
Mitochondrial disorders
What is threshold effect?
Different proportion of abnormal mitochondria may be required to cause disease in different tissues
If a male or female is affected with a mitochondrial disease, what is his/her family history?
Mother surely has the disease.
Father is not affected/not predictable.
If father is affected, what are the chances among children?
NONE of the children will be affected.
(presumed: mother is normal)
Can an affected father transmit the disease to his his children?
NO.
No transmission from father.
Which genetic inheritences have no male-to-male transmission?
X-linked dominant
X-linked recessive
Mitochondrial disorders
Which genetic inheritences have no male-to-female transmission?
Mitochondrial disorders
If mother is affected, what are the chances among children to inherit the disease?
All children will inherit the disease (sons/daughters all)
(father is normal/affected does not matter)
Which systems are involved commonly?
Muscles (Myopathy), brain (neurological diseases), eye (retinitis pigmentosa), heart, GIT
How is the correlation between genotype and phenotype in mitochondrial disorders?
Poor
Result of muscle biopsy in mitochondrial diseases
Histology: classical ‘red-ragged fibres’
(more in MERRF syndrome)
What do ‘red-ragged fibers’ indicate?
Increased number of mitochondria
Which nature of an organ is affected by mitochondrial diseases?
Organs that are highly dependant upon oxidative metabolism (e.g. muscles)
What is LHON?
Leber’s hereditary optic neuropathy
(AKA Leber’s optic atrophy)
What is the underlying pathology of LHON/Leber’s optic atrophy?
Degeneration of retinal ganglion cells (RGCs)
What is the first presentation of LHON/Leber’s optic atrophy?
Sudden blurring/cloudiness of central vision
(one/both eyes)
What is Leigh disease?
1. Subacute necrotising encephalopathy
2. Retinitis pigmentosa
2. Psychomotor regression:
- Cognitive impairment
- Ataxia
- Weakness
Commonly death within 2-3years due to respiratory failure
What is Usher’s syndrome?
Sensorineural deafness (non-progressive partial/total)
+
vision loss (due to retinitis pigmentosa) (worsen over time)
What is MELAS syndrome?
ME = Mitochondrial encephalomyopathy
LA = Lactic acidosis
S = Stroke like episodes
(also myopathy)
What is MERRF?
Myoclonus Epilepsy with Red Ragged Fibres
Can diabetes mellitus be mitochondrial disorder?
Yes, there are some mitochondrially inherited diabetes mellitus
What are the features of Pearson syndrome?
Sideroblastic anaemia +
Exocrine pancreatic dysfunction
What is the prognosis of Pearson syndrome?
Most are fatal in infancy
If Pearson syndrome survive to adulthood >>> what happens?
they develop Kearns-Sayre syndrome
What is the age of onset for Kearns-Sayre syndrome?
<20years
What is the triad of Kearns-sayre syndrome?
External ophththalmoplegia
Retinitis pigmentosa
Heart block
What is external ophththalmoplegia?
weakness of eye muscles (ocular myopathy)
What are the features of external ophthalmoplegia in Kearns-Sayre?
Ptosis
Symmetrical loss of eye movements (side to side mainly)
(so, usually no diplopia)
What are the features of retina in Kearns-Sayre?
Retinitis pigmentosa
Night blindless
What are the features of heart in Kearns-Sayre?
Cardiomyopathy
Heart block
Syncope
Heart failure
What are the features of ear in Kearns-Sayre syndrome?
deafness
vestibular function loss/loss of balance
What are the CNS features of Kearns-Sayre syndrome?
dementia
raised protein in CSF
sometimes:
seizures, tremor, stroke before 40years
What are the overall common features of Kearns-Sayre syndrome?
Triad:
- External ophththalmoplegia
- Retinitis pigmentosa
- Heart block
Eye features:
- external ophthalmoplegia (ptosis, side-to side loss of eye movement)
- Retinitis pigmentosa
- Night blindness
Heart features:
- Cardiomyopathy
- Heart block
- syncope
- Heart failure
Ear features:
- deafness
- vestibular function loss (loss of balance)
CNS features:
- dementia
- raised protein in CSF
- seizure, tremor
- maybe, stroke <40years
Others:
symptoms releated smooth/skeletal muscle myopathies in different organs
What is NARP?
Neuropathy
Ataxia
Retinitis Pigmentosa
Progressive neurodegenrative disorder
