Mitochondrial Cytopathies

Abstract

Mitochondrial cytopathies represent a heterogeneous group of multisystem disorders which preferentially affect the muscle and nervous systems. They are caused either by mutations in the maternally inherited mitochondrial genome, or by nuclear DNA-mutations. Today, approximately 200 different disease causing mutations of mitochondrial DNA (mtDNA) are known, and due to the increased knowledge about nuclear genetics during the last few years, more and more nuclear mutations are being described. Owing to the non-uniform distribution of mitochondria in tissues and the co-existence of mutated and wildtype mtDNA (heteroplasmy) in these organelles, these disorders may present with a huge variety of symptoms, even if the same mutation is involved. Diagnostic investigations should include the measurement of serum and CSF lactate, neuroradiological tests and a muscle biopsy to show the characteristic ragged-red fibres and cytochrome c oxidase deficient cells and also to provide material for genetic analysis. To date, the treatment of these diseases remains supportive and should focus on typical complications such as cardiac dysrhythmia and endocrinopathy.

MELAS: clinical features, muscle biopsy and molecular genetics

“…The onset of this disease occurs before age 40 and is often seen in childhood, with gradual deterioration 3,4,14 . Clinical symptoms are highly variable across patients 2 . The most common feature in MELAS is episodic headaches with vomiting; this symptom was present in almost all patients 3,4,15 .…”

“…We suggest that the second genetic diagnostic test should be the PCR/RLFP for T3271C 7,9,13 . MELAS could be also caused by mtDNA point mutations in other genes, as the tRNA Phe , tRNA Val , tRNA Lys , COXIII, ND1, ND5 or rRNA, or by small-scale mtDNA deletions 2,7 . However, as the tRNA Leu(UUR) mutations are still the most commonly involved in the MELAS phenotype, we also speculate that molecular analysis of this gene by direct sequencing should be the third molecular test in MELAS patients 7,24 .…”

“…Mitochondrial encephalomyopathies are a heterogeneous group of clinical syndromes, with various biochemical defects of the respiratory chain due to primary defects in cellular mitochondria [1][2][3][4][5] . Mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) is one of occurring mitochondrial disease which includes in its definition encephalopathy, frequently with seizures and progressive dementia; stroke-like episodes at a young age; and biochemical evidence for mitochondrial defects, such as lactic acidosis or ragged-red fibers (RRF) in the muscle biopsy 3,4,6 .…”

Recent Advances in the Molecular Pathogenesis of Dystonia-Plus Syndromes and Heredodegenerative Dystonias

“…Other mitochondrial enzymatic abnormalities have been described, including defects in pyruvate dehydrogenase and respiratory complexes I, II, IV and V [78]. Leigh syndrome may be inherited in a maternal, X-linked or autosomal recessive fashion.…”

Mitochondrial Encephalomyopathy Associated with Diabetes Mellitus, Cataract, and Corpus Callosum Atrophy

“…Mitochondrial disorders preferentially affect the muscle and nervous systems (2) but they may also affect the endocrine glands, heart, ears, gastrointestinal tract, liver, kidneys, bone marrow, and dermis (3).…”