Examples up regulate the synthesis of insulin that

Examples of
Mitochondrial Genetic Disorders in human:

inherited diabetes and deafness:

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MIDD is a
mitochondrial induced genetic disorder that is followed by loss in hearing
capability and diabetes. MIDD is characterized by sensorineural deafness
and hyperglycemia in which sugar levels of the blood raised to the hazardous
level due to limited availability of insulin hormone.1


than deafness and diabetes, Symptoms of MIDD includes cardiomyopathy,
dysfunction of kidney and problems related to GI track.2


beginning of diabetes in MIDD takes place between the age of 15 to 70 years
(average is 32.8 to 38.8 yr), while the age of inception of deafness occurs at
the mean age of 33.2 years with a progressive nature.3


exact commonness of MIDD is
not known but around 0.2 to 3% of the patients of diabetes suffer from MIDD.4


MIDD is the consequence
of point mutation in MT-TL1, MT-TE and MT-TK
genes which codes for mt tRNA for Leucine, Glutamic Acid and
Lysine respectively.

Mitochondria plays an important role in the
pancreatic beta cells by maintaining the sugar level of the body, as the sugar
increases mitochondria up regulate the synthesis of insulin that will utilize
glucose and decrease blood sugar level. But mutation in any one of the MT-TL1,
MT-TE and MT-TK gene results in diminished capability of the
transfer RNA to attach new amino acids to the developing polypeptide chain,
which ultimately results in the decline of the function of mitochondria to
produce insulin. Hence these point mutations reults in diabetes.5

MT-TL1 gene codes for tRNA that is known as tRNALeu(UUR).
UUR is the triplet codon of Leucine, where R can either be A or G.  it is coded by the sequence of nucleotides
ranging from 3230 to 3304. The point mutation that prevails in this gene is
replacement of Adenine with Guanine at the nucleotide position of 3243 hence
known as A3243G6

gene codes for tRNA of
lysine amino acid. It is coded by the sequence of nucleotides ranging
from 8295 to 8364. The point mutation that prevails in this gene is replacement
of Adenine with Guanine at the nucleotide position of 8296 hence known as

gene codes for mt
tRNA of Glutamic acid. It is coded by the sequence of nucleotides ranging
from 14674 to 14742. And this nucleotide range falls in L-strand of the DNA. The
point mutation that prevails in this gene is replacement of Thymine with
Cytosine at the nucleotide position of 14709 hence known as T14709C. 8


is inherited in a mitochondrial pattern, which is also known as maternal
inheritance. This pattern of inheritance applies to genes contained in
mitochondrial DNA. Because egg cells, but not sperm cells, contribute
mitochondria to the developing embryo, only females pass mitochondrial
conditions to their children. 9


Leigh Syndrome is the syndrome that involves in the
loss of various movement and mental capabilities (also known as psychomotor
regression) with failure in respiratory system that within 3 years, ultimately
results in the death of the patient. It is a genetic disorder that can either
be caused by mutation in nuclear DNA or mitochondrial DNA, with more chances in
nuclear DNA. 10


of the syndrome includes; Loss in appetite, seizures, vomiting, crying
(continuos one) and irritability. While with the progression of the disorder
body undergo different problems including weakness and continuos contraction of
muscles. It also results in lactic acidosis that eventually leads to kidney and
respiratory functions impairment. 11

Onset Age

This neurological syndrome most commonly occurs at
the 1st year of child’s life. 12


As far as prevalence of Leigh syndrome is concerned
it affects 1 person in every 30,000 to 40,000 individuals at the time of
birth.  Mt DNA induced disorder are less
prevalent it affects 1 out of 100,000 to 140,000 individuals at the time of
birth. 13


In total 75 genes are responsible efor Liegh
Syndrome. Out of which only 20% mutations are present in mtDNA. As it is known
fact that most of the mitochondrial genes are involved in the the production of
energy productions mechanism. Mitochondria is involved in the oxidative
phosphorylation which requires oxygen for the convertion of food into useable
energy i.e. ATP. In total there are 5 protein complexs that are involved in
this process of oxidative phosphorylation. Most of the mutations, responsible
for leigh syndrome, influence the structure of these complexes that ultimately
leads to leigh’s syndrome.14

Fig 1# different complexes are
involved in oxidative phosphorylation

Mutations is complex 1

1 is also known as NADH:ubiquinone
oxidoreductase, which is the most prevalent cause of Leigh syndrome out of 75
genese responsible for the disorder, 25 (both in nuclear and mitochondria) are
responsible for mutation in complex 1. Following are the mutations in
mitochondrial DNA.


Mutations in Complex 4

like complex 1, mutation in complex 4 can also be coded by mitochondrial DNA
.i.e. MTCO3.

Mutations in Complex V

gene mutation is the most frequent mutation caused by mitochondrial DNA, and
this mutation affects the assembly of complex 5.  The normal product of the gene codes for ATP
synthase enzyme that produce in oxidative phosphorylation step of energy
generation. Around 10% of the patients of Leigh syndrome are affected with this

Fig 2# genes that are involved in
complexes of oxidative phosphorylation


tRNA Mutations:

above mentioned mutations other mutations also exists that codes for Trna of
mitochondria which are; MTTK, MTTV, MTTL1and MTTW 16.

Pearson syndrome

is a other mt disorder that consists of exocrine pancreas dysfunction and sideroblastic anemia (combination of
sideoblasts  and anemia). 17


Syndrome usually affects 1 person in every million births of the population.18

 Age of onset

disease occurs at the time of birth with death of the patient usually takes
place within three years. This disease is due to lactic acidosis and septic
risks. While if some lucky soul survives he gets suffered from ataxia,
Kearns-Sayre syndrome, pigmentary retinitis and even myopathy.19

Genetic Basis:

syndrome is due to a large, single deletion mutation ranging from 1K to 10k
Nucleotides. Around 20% of the patients undergo deletion of 4997 nucleotides.20


Fig 3# mtDNA with pointing out which
set of genes are involved in which syndromes.

Effects of Mutation:

mutations in mtDNA causes the deformation of proteins that are involved in the
process of oxidative phosphorylation, hence cells deplete out of the energy.
Till now it is absolutely not clear that how does these deletion mutations
results in symptoms of  Pearson’s

major effect of this disorder is dysfunctioning of Bone marrow which involves
hematopoitic cells that leads to the formation of RBCs, WBCs and Platelets.

Fig 4# Bone marrow dysfunctioning
involves blood cells problems


are the symptom of Pearson Syndrome:


Anemia is the major symptom of
Pearson syndrome which involves in reduction of RBCs which results in general
weakness, pale coloration of body and early tiredness.

Fig 5# Anemia a
consequence of Pearson syndrom


This is the condition of reduced
WBCs which leads to reduction in immunity of the body.

Fig 6# Reduction of WBCs
in the patients of Pearson’s syndrome.



This is the condition of less platelets in the body. Whose consequence
is reduction in cloting capacity of the blood. That may results in excessive
loss of blood as a result of injury or cuct.

Fig7# thrombocytopenia
condition in the patients of Pearson syndrome


Other symptoms of person syndrome includes; Diarrhea, hard
to overfeed, pain in stomach and even diabetes (in extreme and limited cases).
Other patients may have effects on kidney, eyes, heart, ears and liver.22