Transient Corneal Edema and Left Hemisphere Dysfunction in Pearson Syndrome

Abstract

Pearson syndrome is a rare mitochondrial disorder of infancy manifested by sideroblastic anemia, pancytopenia, exocrine pancreatic insufficiency, and variable involvement of the kidneys and liver (1). Large deletions in the mitochondrial genome lead to derangement of oxidative metabolism and a decreased mitochondrial energy supply (2). The neurologic manifestations include hypotonia, developmental delay, ataxia, and tremor (3). There are no reported ophthalmic findings. Patients who survive infancy may later develop Kearns-Sayre syndrome (KSS) (4). Persistent corneal edema attributed to endothelial dysfunction has been reported in KSS (3,5,6) and in chronic progressive external ophthalmoplegia (CPEO) (7), but transient corneal edema has not been reported in any mitochondrial disorder. We recently examined a 3-year-old girl with Pearson syndrome who developed transient corneal edema in conjunction with transient left cerebral hemispheric dysfunction manifesting as left gaze deviation and right hemiparesis. Such phenomena have not been reported previously in Pearson syndrome. Pearson syndrome was diagnosed in the patient at 12 months of age after she presented with transfusion-dependent sideroblastic anemia. Testing revealed a large mitochondrial DNA deletion. She later developed pancreatic insufficiency and Fanconi renal disease. At 3 years and 9 months of age she was admitted for severe sepsis due to Salmonella infection. Before this admission, she had had no known neurologic abnormalities. A normal ophthalmologic examination with a pediatric ophthalmologist had occurred 1 month before admission. She required intubation, pressor support, and chest compressions for episodes of cardiac arrest. After extubation, she exhibited lingering reduced consciousness, left gaze deviation, and right hemiparesis. She failed to respond to verbal stimuli. A right extensor plantar reflex was present. Her eyes were fully deviated to the left and did not cross the midline to command, visual stimuli, or the oculocephalic maneuver. Both corneas were cloudy. Results of dilated fundus examination were unremarkable. Brain MRI obtained during this episode showed diffuse parenchymal volume loss but was otherwise unremarkable. MRI spectroscopy was not performed. Electroencephalography showed diffuse slowing but no epileptiform activity. The hemiparesis, gaze deviation, and corneal edema had resolved within 1 week. The patient was discharged in her baseline state. Stroke-like manifestations are well documented in many mitochondrial disorders, most notably the condition called mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) (8), but not in Pearson syndrome. Reversible corneal edema has not been described in any mitochondrial disorder. We presume that in our patient this ocular manifestation, together with transient cerebral hemispheric dysfunction, were related to an exacerbation of impaired mitochondrial function triggered by the sepsis (9) Lee et al (3) described a 3-year-old girl with Pearson syndrome who was discovered to have persistent corneal haze and early retinitis pigmentosa in conjunction with acute pancreatitis. She died 4 months later without autopsy. Chang et al (5) reported the histopathologic results on the post-mortem cornea of a patient with KSS who died at age 27 and had had persistent corneal edema since age 4. It showed edema of the epithelium with areas of bullous separation, thickening of Descemet's membrane, and absence of the endothelium and Bowman's membrane. Boonstra et al (6) reported stromal and epithelial corneal edema by biomicroscopy as the initial sign of KSS in a 6-year-old boy. At age 14, biomicroscopic examination showed endothelial edema as well. Nakagawa et al (10) described improvement of corneal edema in an 11-year-old boy with KSS during treatment with antioxidants. Brain MRI performed during stroke-like episodes in MELAS typically shows transient restricted diffusion predominantly affecting gray matter (11), a feature not seen in our patient. It is possible that a later MRI would have shown abnormalities. Magnetic resonance spectroscopy or positron emission tomography, reported to show abnormalities in mitochondrial disorders in which MRI appears normal might also have marked the left hemisphere dysfunction (12,13). Anna C. Momont, MD Jonathan D. Trobe, MD Kellogg Eye Center Department of Ophthalmology and Visual Sciences University of Michigan Ann Arbor, Michigan [email protected]