MITOCHONDRIAL DISEASE TESTING

An Overview about MITOCHONDRIAL 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.