Ihese conditions are discussed together because of a common overlap. y Most cases are spontaneous and have mtDNA deletions. Over 100 different deletions have been identified; 90 percent occur between the large arc between the two points of replication. Deleted mtDNAs localize to distinct regions along muscle fiber, whereas normal mtDNAs are evenly distributed, resulting in a periodic respiratory deficiency along the muscle fiber. Ihe loss of tRNAs is rate limiting in these areas, causing deficits in protein synthesis and oxidative phosphorylation. Duplications may occur spontaneously or be maternally inherited and are detected in quiescent (muscle) and actively dividing tissue (lymphocytes). Ihe mechanism of their generation is unclear. Ihe exact incidence of these conditions is unknown. Most all cases are sporadic.
If ophthalmoplegia before the age of 20 years is accompanied by atypical retinitis pigmentosa, mitochondrial myopathy, along with cardiac conduction defects, a cerebellar syndrome, or elevated CSF protein (above 100 mg/dl), this constellation is termed KSS. Chronic progressive ophthalmoplegia with onset after age 20 is termed CPEO and, if coupled with a variety of other manifestations, CPEO-plus. Ihese manifestations are many: lactic acidemia; eye and ear findings, including pigmentary retinopathy, optic atrophy,
and hearing loss; cardiac conduction defects, arrhythmias, and dilated or hypertrophic cardiomyopathies; CNS dysfunction, including dementia, seizures, and ataxias; peripheral nervous system damage, including motor/sensory neuropathies; mitochondrial myopathy; and mutisystemic organ involvement in the form of diabetes mellitus, hypoparathyroidism, glomerulosclerosis, proximal renal tubule dysfunction, gastrointestinal motility problems, and respiratory failure.
Conditions to exclude include other mitochondrial diseases, primarily MERRF and MELAS; any disease causing ophthalmoplegia when that is the sole presenting symptom, especially myasthenia gravis; other diseases that cause multisystem involvement, such as collagen vascular diseases, particularly systemic lupus erythematosus; and in the appropriate setting, Lyme disease (caused by infection with Borrelia burgdorferi) or Whipple's disease. Ihe ultimate diagnosis is made by muscle biopsy and mtDNA analysis. Ihere is no proven specific treatment, although coenzyme Q10 and carnitine have been used. Implanted cardiac pacemakers can be used for conduction defects. Associated endocrine abnormalities--growth hormone deficiency, diabetes mellitus, or hypoparathyroidism--can be treated medically. Although these conditions are considered chronic, complete heart block may result in sudden death.
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