The document provides information on various mitochondrial disorders including Kearns-Sayre syndrome, MELAS syndrome, and Mitochondrial Neurogastrointestinal Encephalopathy Syndrome (MNGIE). It describes the symptoms, causes, and diagnosis of each disorder. Kearns-Sayre syndrome is characterized by progressive paralysis of the eye muscles and can affect multiple systems. MELAS syndrome causes seizures, headaches, and muscle weakness and is caused by mitochondrial DNA mutations. MNGIE is a rare multisystem disorder causing gastrointestinal problems and is caused by mutations in the TYMP gene encoding thymidine phosphorylase.
2. Mitochondria is present in the
cytoplasm of cell.
It contains two membrane
Mitochondria have round chromosome
Multiple copy number in the cell
Mutation rate is high .
3. Supply energy to cell in form of
ATP
Generate and regulate reactive
oxygen species
Regulate apoptosis
Serves as cellular site for the
following metabolic pathways-
Electron transport chain
Tricarboxylic acid cycle
Beta oxidation of fatty acid
Gluconeogenesis
Urea synthesis
4. Circular double stranded ,
composed of heavy and light
chains
Contains 16,569 bp
Encodes 13 protein, 22tRNA
,2rRNA
Smaller number of gene
Less effective repair
mechanism
Higher mutation rate
6. Due to defects in mitochondrial DNA
Due to defects in nuclear DNA
Defects in mitochondrial DNA
•Single base pair variants
•Mitochondrial DNA rearrangement ( deletion, insertion)
7. S.
N.
MITOCHONDR
IAL DNA
DISORDER
CLINICAL
PHENOTYP
E
mtDNA
GENOTYP
E
GENE STATUS INHERITAN
CE
1 Kearns-Sayre
syndrome
Progressive
myopathy,
ophthalmopl
egia,
cardiomyopat
hy
A single,
large scale
deletion
several
deleted
genes
Heteroplas
mic
Usually
sporadic
2 CPEO ophthalmopl
egia
a single,
large scale
deletion
Several
deleted
genes
heteroplas
mic
Usually
sporadic
3 Pearson
syndrome
Pancytopoeni
a,
Lactic
acidosis
A single,
large scale
deletion
Several
deleted
genes
Heteroplas
mic
Usually
sporadic
4 MELAS Myopathy,
encephalopat
hy lactic
acidosis,
stroke-like
episodes
3243A>G;
3271T>C
Individual
mutations
TRNL1
ND1
and
ND5
Heteroplas
mic
heteroplas
mic
Maternal
maternal
9. Classification of mitochondrial disorders
caused by nuclear genes
S.N
.
MECHANISM GENE
INHERITANCE
PHENOTYPE
1 Multiple mtDNA
deletions
TP
ANT1
TWINKLE
POLG
AR
AD
AD, AR
AD, AR
MNGIE
adPEO
adPEO, IOSCA
adPEO, arPEO, SANDO,
parkinsonism
2 mtDNA depletion POLG
TK2
SUCLA2
DGUOK
MPV17
AR
AR
AR
AR
AR
Alpers syndrome
MM, SMA
LS
Alpers syndrome
Alpers syndrome
3 RC subunit defect NDUSFx
NDFVx
SDHA
AR
AR
AR
LS, GRACILE
LS
LS
10. 4 Ancillary protein defect BCS1L
SURF1
SCO2
COX15
ATP12
AR
AR
AR
AR
AR
LS
LS
LS, hypertrop
cardiomyopat
Hypertrophic
LS
5 CoQ synthesis defect COQ2, PDSS2 AR Encephalomy
Tubulopathy,
6 Iron metabolism defect ALAS2, ABCB7
FRDA
x- linked
AR
Sideroblastic
Friedreich’s at
7 Motility defect KIFSA AD Spastic parap
8 Fusion defect MFN2
OPA1
AD
AD
CMT2A
Optic nerve a
9 Fission defect DLP1 AD Microcephaly
lactic acidosis
11.
12.
13. Introduction-
KSS is an uncommon neuromuscular
condition
That affects those below age 20 years
The condition is generally characterized
by a progressive paralysis of the eye
muscles
Condition is a multi-systemic disorder
that is progressive and can gravely affect
the life of the affected child.
Symptoms
Eyelid drooping known as ptosis
Pigmentation of retina
External opthalmoplegia
Cardiomyopathy
Muscles weakness
Deafness
Seizure problems
diabetes
14. CAUSES DIAGNOSIS
Checking the pH and glucose level
in the urine
Check creatinine level in
blood
Confirmatory test is through
muscles biopsy of the orbicularis
KSS occurs spontaneously
In some case inherited by
mitochondria , autosomal dominant ,
or autosomal recessive inheritance
KSS is the result of deletion in
mitochondrial DNA
Common 5kb mtDNA deletion,
deletion/duplication ,A3242G
Responsible gene are
ANT1,TWINKLE,POLG
15. INTRODUCTION
Rare disorder affecting the
muscles and nervous system
The symptoms of this disorder
begin as early as childhood
And the signs became evident
before the persons attains 15years
SYMPTOMS
It can cause seizures
Intense headaches
Muscles weakness
Loss of vision and hearing
Vomiting
Fatigue and abdominal pain
Loss of memory
CAUSES
This syndrome is caused due
to defective mutation of
mitochondrial DNA
Repeated mutation
Inherited by birth
A3243G point mutation in
tRNA-80%
DIAGNOSIS
Based on the symptoms of the
affected person, the doctor
would suspect MELAS
syndrome.
Brain biopsy
16.
17. INTRODUCTION
Mitochondrial Neurogastrointestinal
Encephalopathy Syndrome
MNGIE is rare multisystem
disorder
Characterized by
progressive degeneration of
the muscles of the
gastrointestinal tract causing
gastrointestinal dysmotility
Weakness of extra – ocular
muscles
Degeneration of peripheral
nerves causing altered
sensation
SYMPTOMS
Vomiting
Nausea
Diarrhea
Abdominal pain
Numbness or sensation altered
Ptosis
CAUSES
MNGIE is caused by changes in the TYMP
gene encoding thymidine phosphorylase
MNGIE caused by depletion,deletion or
point mutation.
DIAGNOSIS
A diagnosis of MNGIE is
suspected based upon detailed
patient history
MRI
A diagnosis may be confirmed
biochemically by
demonstratating low TP
enzyme activity in