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Although systemic disease is usually evident during infancy, ocular symptoms such as ptosis and ophthalmoplegia may not be apparent until adulthood in those that survive. The ocular myopathy in adults can resemble Kearns-Sayre syndrome (530000) as the result of a phenotypic shift from a predominantly hematopoietic disorder to a mitochondrial myopathy. Bilateral zonular cataracts and strabismus have been reported in a 3 year old male. A midperiphery pigmentary retinopathy has been observed. Endothelial cell failure leads to corneal edema.
Low birth weight, failure to thrive, hypoplastic anemia and exocrine pancreatic dysfunction are often seen in infancy. Precursor cells in the marrow show typical vacuolization. Malabsorption and insulin-dependent diabetes often develop. The pancreas and bone marrow may become fibrotic. Patients with the classic syndrome as a child can develop features of the Kearns-Sayre syndrome if they survive childhood. Progressive muscle weakness in pharyngeal, facial, neck, and limb muscles is sometimes seen in older individuals and muscle biopsy reveals ragged-red fibers characteristic of mitochondrial disease. Some patients have an organic aciduria and others develop hepatic failure with elevated transaminase, bilirubin and lipid levels. Kidney damage results in Fanconi syndrome. Young children may recover from the refractory anemia eventually but metabolic acidosis with life-threatening lactic acidosis is a constant threat and responsible for many childhood deaths.
Deletions in mtDNA involving numerous genes are responsible for this condition. As a result, it is maternally transmitted but somewhat inconsistently due to mitochondrial heteroplasmy. Both sexes are affected. The irregular size of the mtDNA deletions and the tissue distribution of affected mitochondria results in considerable variation in clinical expression. Defective oxidative phosphorylation seems to be the underlying cause of many of the signs and symptoms.
This multisystem disease requires careful monitoring throughout life. Blood transfusions may be required and careful attention needs to be given to nutrition and metabolic dysfunction. A few patients have required insulin. In spite of vigorous treatment of electrolyte imbalances, correction of acidosis, and hormonal supplements, many patients do not survive beyond childhood. Organ failure requires individualized treatment.