An Overview aboutMITOCHONDRIAL DISEASE TESTING

INTRODUCTION

❖ Mitochondrial disease is a chronic, genetic disorder that occurs when the mitochondria of the cell fail to produce enough energy for cell or organ function.

❖ Mitochondrial disease result from failures of the mitochondria, specialized compartments present in every cell of the body.

❖ More than 90% of the energy needed by the body are created by the mitochondria.

❖ The energy produced by these mitochondria is responsible for sustaining life and support organ function.

❖ Mitochondria is known as the powerhouse of the cell.

Cause of Mitochondrial Diseases ● Mitochondrial disease or disorders may be caused by mutations, in

mitochondrial DNA or in nuclear genes that code for mitochondrial components.

● Also, these problems may be the result of the acquired mitochondrial dysfunction due to the adverse effects of drugs, infections or environmental causes.

Types of mitochondrial diseases● Mitochondrial myopathy

● Diabetes mellitus and deafness

● Lebers hereditary optic neuropathy

● Leigh Syndrome

● Myoclonic epilepsy with ragged red fibers

● MEALS Syndrome

● Mitochondrial DNA depletion syndrome

● Myoneurogenic gastrointestinal encephalopathy

Diagnosis Method❖ Mitochondrial disease are usually detected by analyzing muscle samples,

where the presence of these organelles is higher.

❖ The most common tests for the detection of these disease are

● Southern blot to detect big deletions or duplications

● PCR and specific mutation analysis

● Sequencing

Southern blot

● This is a laboratory test used to detect a specific DNA sequence in blood or tissue sample.

● Various steps in southern blot

➢ DNA Digestion➢ Gel Electrophoresis➢ Blotting➢ Probe labeling➢ Hybridisation and Washing➢ Detection

PCR and specific mutation analysis

➔ This is a technique which is used to make many copies of specific DNA region.

➔ Various steps of PCR includes

◆ Denaturation

◆ Annealing

◆ Extension

CONCLUSION❏ There are several laboratories all over the world where mitochondrial

disease testing has been done.

❏ Most diagnostic algorithms recommended the evaluation of selected mitochondrial biomarkers in blood, urine and spinal fluid.

❏ These typically include measurements of lactate and pyruvate in plasma and cerebrospinal fluid, plasma, urine and CSF amino acids, plasma acylcarnitines and urine organic acids.

❏ Primary mitochondrial disorders are caused by mutations in the maternally inherited mtDNA or one of many nDNA genes.