MITOCHONDRIAL ENCEPHALOMYOPATHIES

BY

Caroline Karunya Ponnarasi Kanagaraj

Group-IV

INTRODUCTION

The mitochondrial myopathies are a clinically

heterogeneous group of disorders with structural

mitochondrial abnormalities on skeletal muscle biopsy.

Their morphologic signature is the “ragged red fiber” seen

with the modified Gomori stain, containing accumulations

of abnormal mitochondria.

Patients may present with:

– Kearns-Sayre-Daroff syndrome

– myoclonic epilepsy [myoclonic epilepsy, ragged red fiber

syndrome, (MERRF)]

– mitochondrial myopathy, encephalopathy, lactic acidosis, and

stroke like episodes (MELAS).

These various syndromes are caused by separate

abnormalities of mitochondrial DNA.

VITAMINS

V-Vascular

I-Infection

T-Trauma

A-Autoimmune

M-Metabolic

I-Inherited

N-Neoplasm

S-Seizures

MELAS

Six different Point Mutation:

80% of cases have a A to G point mutation in the

tRNA (Leu) gene at bp 3243

7.5% of cases have a T to C point mutation in the

tRNA (Leu) gene at bp 3271

All of these mutations are heteroplasmic

Heteroplasmic= within a single cell,there is a mixture of

mitochondria,some containing mutant DNA and some

containing normal DNA.

This feature of mitochondrial diseases might offer a

solution to the varied rates of progression and onset of

the disease.

PATHOPHYIOLOGY

Abnormal Mitochondria do not metabolize pyruvate

Excess pyruvate is reduced to Lactic acid which

accumulates in blood and other fluids.

Large clumps of abnormal mitochondria form in the

walls of small arteries and capillaries in the brain and

muscles.

Symptoms

Short stature

External ophthalmoplegia (a rare symptom in

MELAS) Paralysis of the muscles that open eyelids, and

control eye movement Results in drooping of the

eyelids.

Musculoskeletal:

Overall muscle weakness

Exercise intolerance

Neurological:

Seizures

Recurrent severe headaches and migraines

Altered states of consciousness

Dementia (loss of intellectual ability)

Ataxia

Temporary local paralysis

Sensorineural hearing loss – damage to the nerve of the

inner ear, resulting in deafness

•

Other symptoms :

Vomiting

Loss of bowel control

Kidney dysfunction

Hormonal problems causing diseases like diabetes

mellitus

Cardiac conduction block – problems in the electrical

system of the heart that controls heartbeat

MERRF

MERRF – Myoclonic epilepsy with ragged red fibres

Myoclonus:

The sudden contraction of muscles, causing brief

jerking movements

Epilepsy:

The condition of having severe, recurrent seizures

Ragged red fibres :

Abnormal mitochondria accumulated under the

muscle membrane, appear as red strands in muscles,

when stained

CHARACTERSTICS

MERRF generally affects children and adolescents or

even adults at times, and almost always occurs after

normal development in infancy.

MERRF is very rare with prevalence being less than 1 in

100 000.

No ethnic or gender predisposition is found in MERRF.

SYMPTOMS

Neurological:

Myoclonus

Generalized Epilepsy

Ataxia

Dementia

Ocular:

Retinitis Pigmentosa – a group of diseases

characterized by

Swelling of cells in the retina

Vision loss in the night

Peripheral vision loss

Central vision loss

•

External ophthalmoplegia/ophthalmoperesis

Paralysis/weakness of the muscles that open eyelids

and move the eyes, resulting in restricted eye

movement and droopy eyes.

Physical appearance:

Short stature( may be present)

Other Symptoms:

Exercise intolerance

Cardiomyopathy – disease affecting the heart muscle,

which may lead to heart failure

Lipomas – benign tumours found beneath the skin, that

are composed of fatty tissue

Testing

Body fluids:

A high lactic acid and pyruvic acid (acids found in the

mitochondria) concentration in cerebrospinal fluid

(CSF) and blood

An increase in protein concentration in CSF

Muscle Biopsy:

Abnormal mitochondria from under the muscle tissue

membrane appear as “ragged red fibres” under a

microscope

•

Brain scans using MRI or CT reveal:

Abnormal signals from certain

brain areas, often from the

basal ganglia

scan of a healthy brain.

MRS testing reveals increase in lactate concentration in

the brain

TREATMENT

Medical care under the following specialists may be

required: neurologist, medical geneticist,

ophthalmologist and cardiologist.

There is no known treatment for the underlying disease,

which is progressive and fatal.

Patients are managed according to what areas of the body

are affected at a particular time.

Enzymes, amino acids, antioxidants and vitamins have

been used, but there have been no consistent successes

reported.

CONCLUSION

After coming to know about these diseases and the worst

thinking's of the mankind about a child ,I think you

would have got the motivation to live long and stay

strong for anything and you will realize that your life is

not that tough compare to those who are suffering from

an incurable diseases.

Till now doctors all around through world are still

finding medicine and ways to cure this diseases .

I wish that someone here in the classroom will be the

first one who finds the cure for this diseases which we

discussed now in the future and help kids like who are

undergoing these unwanted sayings.