Mitochondrial Encephalomyopathies: Diseases of Mitochondrial DNA
Two genomes control mitochondria: mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Diseases caused by nDNA mutations: Mendelian inheritance (see Chapter 99). Diseases caused by mutations in mtDNA: maternal inheritance or sporadic; mitochondrial encephalomyopathies.
General Principles
Mitochondrial Genetics
Human mtDNA encodes proteins in respiratory chain, translational proteins.
Each cell contains multiple copies of mtDNA (polyplasmy). Both mutant and wild-type mtDNA may coexist in individual (heteroplasmy). Manifestations of mtDNA mutation depend on amount of heteroplasmy (threshold effect). Distribution of mitochondria in tissue continues to change after birth (mitotic segregation); phenotype changes over time. Inheritance maternal (mitochondria contributed by oocyte, not sperm); distinguished from autosomal dominant disorders by absence of paternal transmission.
Multiple deletions in mtDNA may result from mutation in nDNA; inheritance is autosomal (dominant or recessive).
Clinical Features
Common neurologic findings: ophthalmoplegia, myopathy, peripheral neuropathy, sensorineural deafness, pigmentary retinopathy.
Prevalent systemic abnormalities: short stature, cardiomyopathy, cardiac conduction defects, diabetes mellitus, other endocrine disorders, lipomatosis.
Laboratory data: lactic acidosis in blood and CSF.
Pathology: ragged red fibers (RRFs) in muscle fibers (proliferation of mitochondria; not present in all conditions).
Diagnosis: (a) recognize appropriate clinical syndrome; (b) lactic acidosis; (c) RRFs; (d) document impaired respiration in biochemical assay of muscle extracts or isolated mitochondria; (e) identify mutation in mtDNA in blood or muscle. Not all criteria present in each syndrome.Related posts:
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