Syndromes Kearns-Sayre

Figure 10. Ragged-red fibers with peripheral accumulations of mitochondria in muscle from a patient with Kearns-Sayre syndrome (KSS).

The clinical symptoms of mitochondrial diseases are highly varied and include seizures, vomiting, deafness, dementia, stroke-like episodes, and short stature. Although there are many types of mitochondrial disorders, four of the most common types are as follows Kearns-Sayre syndrome, Leber s hereditary optic atrophy, MELAS (mitochondrial encephalopathy, lactic acidosis and stroke-like episodes) and MERRE (myoclonic epilepsy with ragged red fibres). 

Kearns-Sayre syndrome [17] A multisystem disorder characterized by the invariant triad onset before age 20 years, PEO, pigmentary retinal degeneration plus at least one of the following complete heart block, cerebrospinal fluid protein above 100 mg/dl, cerebellar ataxia. Large-scale heteroplasmic mitochondrial DNA deletions are frequently detected in skeletal muscle (rarely in other tissues). 

Articaine has been implicated in an episode of weakness of the limb muscles, fatigue, and anorexia in a patient with a rare respiratory chain disorder due to a genetic defect in mitochondrial DNA (Kearn-Sayre Syndrome). 

A 28 year-old woman with Kearns-Sayre Syndrome, previously exposed multiple times to lidocaine, underwent planned tooth extraction after injection of articaine 1.5 ml (60 mg) with adrenaline (0.009 mg) (168). Within 5 minutes she complained of a feeling of heat, fatigue, weakness, and a desire to sleep. She was unable to walk or stand and had frequent urination. At 20 hours after the injection she had diffuse weakness, reduced tendon and absent patellar reflexes, and sub-clonic Achilles tendon reflexes. She recovered fully 48 hours after the injection. 

Finsterer J, Haberler C, Schmiedel J. Deterioration of Kearns-Sayre syndrome following articaine administration for local anesthesia. Clin Neuropharmacol 2005 28 (3) 148-9. 

L13. Lou, H. C., Correction of increased plasma pyruvate and plasma lactate levels using large doses of thiamine in patients with Kearns-Sayre syndrome. Arch. Neurol. 38, 469 (1981). 

M19. Miiller-Hocker, J., Johannes, A., Droste, M., Kadenbach, B., Pongratz, D., and Hubner, G., Fatal mitochondrial myopathy in Kearns-Sayre syndrome with deficiency of cytochrome oxidase in the cardiac and skeletal muscle An enzyme-histochemical ultra-immunocytochemical fine structural study in longterm frozen autopsy tissue. Virchows Arch. B Cell Pathol. Incl. Mol. Pathol. 52, 353-367 (1986). 

Kearns-Sayre syndrome and dilatative mitochondrial myopathy. Hum. Pathol. 23, 1431-1437 (1992). 

Lestienne P, Ponsot G Kearns-Sayre syndrome with muscle mitochondrial DNA deletion. Lancet 1 885,1988. 

Kearns-Sayre syndrome (ragged red fibre myopathy or oculocraniosomatic syndrome)... 

Characterised by sideroblastic anaemia and exocrine pancreas dysfunction. Usually fatal in infancy. The few patients who survive into adulthood often develop symptoms of Kearns-Sayre syndrome. It is very rare less than 100 cases have been reported. 

Zeviani M, Moraes CT, DiMauro S, Nakase H, Bonilla E, Schon EA, et al. Deletions of mitochondrial DNA in Kearns-Sayre syndrome. Neurology 1988 38 1339-46. 

Large mtDNA deletions account for most cases of ocular myopathy and Pearson s marrow/pancreas syndrome. Ocular myopathy patients can exhibit a variety of clinical symptoms, from mild chronic progressive external ophthalmoplegia (CPEO) to Kearns-Sayre Syndrome (KSS). These diseases are characterized by an early onset of ophthalmoplegia, atypical retinitis pigmentosa, mitochondrial myopathy, and usually cerebellar syndrome and cardiac conduction abnormalities. More than 120 different mtDNA deletions have been identified from patients tissues. Partial duplications of mtDNA have been detected in ocular myopathy and Pearson s syndrome, however, duplications are much rarer than spontaneous deletions in patients with these conditions. Exactly how partial mtDNA duplications arise is unknown. 

KSS (Kearns-Sayre syndrome) CPEO plus retinal degeneration, cardiomyopathy, hearing loss, diabetes, renal failure. 

Eagle RC Jr, Hedges TR, Yanoff M. 1982. The atypical pigmentary retinopathy of Kearns—Sayre syndrome. A light and electron microscopic study. Ophthalmology 89 1433-1440. 

Horwitz, S.J. and Roessmann, U. (1978) Kearns-Sayre syndrome with hypoparathyroidism. Ann. Neurol. 3 513-518. 

Kearns-Sayre syndrome Onset before 20 years of age, characterized by opthalmoplegia, atypical retinitis pigmentosa, mitochondrial myopathy, and one of the following cardiac conduction defect, cerebellar syndrome, or elevated CSF proteins. Deletion of contiguous segments of tRNA and OXPHOS polypeptides, or duplication mutations consisting of tandemly arranged normal mtDNA and an mtDNA with a deletion mutation. 

In healthy people the rate of ketogenesis, and therefore the concentration of acetoacetate and 3-hydroxybutyrate in the blood, will decrease after meals, but may increase in mitochondrial disorders [15, 20]. Increased serum ammonia, creatine kinase or CSF protein concentration is not indicative for a mitochondrial disturbance. If found, urea cycle defects, liver cirrhosis, muscle dystrophy or brain necrosis must be considered. Patients with Kearns-Sayre syndrome and Leigh syndrome, however, often have increased protein concentrations in the CSF. 

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