Mitochondrial Disorders

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problems

Table 2: shows effect of mitochondrial changes (diseases) on heart, liver, ears and eyes function.

Causes:-

MD caused by mutations in mitochondrial DNA or in the nuclear gene .they may be result in disorder due to infection and other environmental causes. Each mitochondrial organelle contains multiple copies of mtDNA. When the cell division takes place then the existing mitochondria segregate randomly between two new cells, then more copies are made by mitochondria. If few copies are defective which are inherited from the mother then mitochondrial division cause most defective copies. Mitochondrial DNA lack the error checking capability due to this mitochondrial mutation occurs frequently. Mitochondrial disorders occur spontaneously. Enzyme that involve in mitochondrial replication if there is defect in that enzyme it may cause mutation which leads to disorder. Nuclear DNA control most mitochondrial function and biogenesis. If there is defect in nuclear-encoded mitochondrial genes it may leads of clinical disease phenotypes including anaemia, dementia, hypertension and lymphoma (masahito tachibana; shoukhrat mitalipovet al).

INHERITENCE AND GENETICS

AUTOSOMAL RECESSIVE INHERITANCE:

AUTOSOMAL recessive inheritance mostly common in mitochondrial disorder including fatty acid oxidation disorders, kerb cycle, nuclear –encoded subunit of the respiratory chain assembly factors and transports. We all have two copies of genes one from mother and other from father. In AUTOSOMAL inheritance if we have one defective copy of gene while other normal copy of gene then we can say it is not defective. If both sperm and egg carried defective copy of gene then the child has not normal copy of the gene. Thus in AUTOSOMAL inheritance 25 % children inherit defective gene from both parents while 25% children have original copy of gene.50% of inherited defective gene from one parent. (herodotos ellinas* and elizabeth a.m et al)

Maternal inheritance:-

Maternal inheritance also known as mitochondrial or cytoplasm inheritance is most complicated to all. Mitochondrial disorders are due to maternal inheritance .examples are LHOH MERRF, NARP and MELAS. In this case children inherited their mitochondrial DNA only from their mother.

Each of our cells contains 2 copies of nuclear gene. We used the concept heteroplasmy in which people have some of mitochondrial DNA normal which means they don’t cause mutation and some mitochondrial DNA not normal or cause mutation. The proportion of Heteroplasmy among maternal family member in the case of homoplasmic they contain normal mitochondrial DNA. It showed that mitochondrial disorders can vary within the family. If a mother which have a mutation in mitochondrial DNA that mutation will pass onto all of her children

X-linked recessive inheritance:-

In x-linked inheritance defective gene locate on x chromosome. Male affected by x-linked inheritance because male have only one x-chromosomes female have 2 x-chromosomes /if one is defected other is normal they do not posse disorder called carrier for that gene. On the other hand if male have defective copy of gene they develop disorder. Mitochondrial disorders which are inherited in this manner are muscular dystrophy haemophilia and colour blindness. The most common type of mitochondrial disorder which has x-linked recessive inheritance is pyruvate dehydrogenase complex deficiency (e1 alpha) is x-linked.

Autosomal dominant inheritance:-

In AUTOSOMAL inheritance only one defective inheritance involves to develop a disorder. They have 50% chance one of the genes in children; with one normal and one defective gene all of individuals may or may not develop disorders. Mitochondrial disorder KEARNS-SAYRE syndrome is AUTOSOMAL dominant inheritance.

Some disorder known to be related with MTDNA

Mutation

Merrf

Meals

Narp

Myoneurogastrointestinal disorder

And encephalopathy (mngie

Aminoglycoside-associated deafness

Diabetes with deafness

Kearns-sayre-cpeo

Leber hereditary optic neuropathy

(lhon

Some other primary disorders of

Intra mitochondrial enzymes

maple syrup urine disease

Nonketotic hyperglycaemia

Hereditary sideroblastic

Anaemia

Otc deficiency

Cps deficiency

Prop ionic academia

Acute intermittent porphyries

Variegate porphyries

Methylmalonic academia

Erythropoietin porphyries Some mendelian (NDNA) disorders of mitochondrial function involving regulation

Of fuel homeostasis

Lethal infantile cardiomyopathy

Friedreich ataxia

Maturity onset diabetes of young

Malignant hyperthermia

Disorders of ketone utilization

Mtdna depletion syndrome

Reversible cox deficiency of infancy

Various defects of the krebs cycle

Pyruvate dehydrogenase deficiency

Pyruvate carboxylase deficiency

Fumarase deficiency

Carnitine palmitoyl transferase

Deficiency

Luft disease

Leigh syndrome (complex i,