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Page 162 Sulaiman et al. J Transl Genet Genom 2020;4:159-87 I https://doi.org/10.20517/jtgg.2020.27

Figure 2. Common diseases associated with mtDNA mutations and the genes involved [24] . LHON: leber hereditary optic neuropathy;
CPEO: chronic progressive external ophthalmoplegia; MERRF: myoclonic epilepsy with ragged-red fibers; MND: motor neuron disease;
MELAS: mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes; PD: Parkinson’s disease

Different types of mitochondrial diseases
Mutations of mtDNA or nuclear DNA (nDNA) that encodes mitochondria components lead to an
ineffective mitochondrial respiratory chain, and hence mitochondrial dysfunction [1,7,15] . The mitochondrial
respiratory chain is an essential pathway for aerobic metabolism. Tissues and organs that are highly
[17]
dependent on aerobic metabolism are prone to mitochondrial diseases . Mitochondrial diseases can
affect single or multiple organ systems [1,7,15] , thus the association with various disease conditions including
neurodegenerative conditions, cardiovascular diseases, neurometabolic problems, cancer and metabolic
diseases such as obesity [3,4,10] . Mitochondrial diseases are considered rare, with a prevalence of 1:1,000,000.
However, recent epidemiological studies suggested that at least 1 in 5000 individuals are affected by
[20]
mitochondrial diseases [18,19] . Mitochondrial diseases may occur at any age , where mutations in mtDNA
account for about 75% of adult diseases but only about 25% of childhood-onset diseases [21,22] . Initially, it
[18]
was postulated that nDNA abnormalities are present in childhood, while mtDNA abnormalities are only
present in late childhood. Recently, many mtDNA diseases also present in childhood, and nDNA mutations
[23]
are also present in adult life . Mitochondrial diseases are classified into several categories, including
primary and secondary mitochondrial diseases (SMD), which are discussed in detail in the next section
[Figure 2].

Primary mitochondrial disease
As the mitochondrial components are inter-dependent of mtDNA and nDNA, most of the primary
mitochondria diseases are due to these components. About 90% of mitochondrial proteins are from nuclear
genes, which include the majority of the OXPHOS system. Also, mtDNA replication, transcription, and
translation are dependent on these nuclear-encoded proteins. Primary mitochondrial diseases (PMD) are
genetically inherited and diagnosed by identifying mutations in the mtDNA or nDNA , which could result
[21]
in mitochondrial dysfunction [Tables 1 and 2]. Such examples are mitochondrial encephalomyopathy, lactic
acidosis and stroke-like episodes (MELAS), neuropathy, ataxia and retinitis pigmentosa (NARP), Leigh
syndrome, myoclonic epilepsy with ragged-red fibers (MERRF), Leber hereditary optic neuropathy (LHON),
Kern-Sayre syndrome (KSS), mitochondrial neurogastrointestinal encephalopathy (MNGIE), and Alpers.