Kearns–Sayre Syndrome Presenting as 2-Oxoadipic Aciduria Bruce A. Barshop, William L. Nyhan, Robert K. Naviaux, Karen A. McGowan, Martin Friedlander, and Richard H. Haas Departments of Pediatrics, Medicine and Neurosciences and The Institute of Molecular Genetics, University of California San Diego, and Department of Ophthalmology, Scripps Clinic and Research Foundation, La Jolla, California 92093 Received August 16, 1999, and in revised form November 9, 1999 A patient with 2-oxoadipic aciduria and 2-amino- adipic aciduria presented at 2 years of age with manifestations typical of organic acidemia, epi- sodes of ketosis and acidosis, progressive to coma. This resolved and the key metabolites disappeared from the urine and blood. At 9 years of age she developed typical Kearns–Sayre syndrome with complete heart block, retinopathy, and ophthalmo- plegia. Southern blot revealed a deletion in the mi- tochondrial genome. © 2000 Academic Press Kearns–Sayre syndrome is a progressive disorder with onset prior to 20 years of age in which multiple organ systems are affected (1). The diagnostic triad includes progressive external ophthalmoplegia, ret- inopathy, and the age of onset, and these are asso- ciated classically with abnormalities in cardiac con- duction, cerebellar signs, and elevated cerebrospinal fluid protein (2). Other nonneurologic manifesta- tions include shortness of stature. In most patients with Kearns–Sayre syndrome there are heteroplas- mic deletions in the mitochondrial DNA (3,4). Some patients have rearrangements or duplications. 2-Oxoadipic aciduria is an abnormality in the ca- tabolism of lysine and tryptophan (5), in which ab- normal quantities of 2-aminoadipic acid are found in body fluids along with 2-oxoadipic acid. Clinical manifestations have been varied, and some reported individuals have been asymptomatic, but acidosis has been documented in infancy and to follow the administration of lysine (5,6). It is the purpose of this report to describe a patient who presented with 2-oxoadipic aciduria and later developed typical Kearns–Sayre syndrome. CASE REPORT S.M. appeared well and was developing normally until the age of 2 years, when she developed a mild upper respiratory infection which was complicated by somnolence which progressed to coma. Dextrostix reading of the glucose in the blood was 90 mg/dl. The ammonia was 53 g/dl. She was resuscitated with intravenous fluid, electrolytes, and glucose and transferred to Children’s Hospital and Health Cen- ter, San Diego, California, where CT scan, MRI, and EEG were normal. She responded and was dis- charged after a few days. Three months later she was again difficult to arouse from sleep and was admitted to the hospital where the concentration of bicarbonate in serum was 16 mEq/liter, and ketonu- ria was prominent. Urine was sent for metabolic evaluation, and she was found to have 2-oxoadipic aciduria and 2-aminoadipic aciduria (Table 1). 2-Aminoadipic acid was also found on analysis of the amino acids of the plasma. She had another episode at 29 months in which development of cough and rhinitis was followed by vomiting and lethargy. On admission to hospital the concentration of glucose was 47 mg/dl and the bicar- bonate was 14 mEq/liter. The urine tested 2+ for ketones. She again responded promptly to paren- teral fluid therapy and was discharged after 2 days. She had been born after an uneventful pregnancy and delivery weighing 3 kg. She was fed a standard commercial formula. Two older half-siblings were well. The father had 2 adult-onset seizures and was treated with dilantin. The mother, who was 30 years of age at birth of the patient, began to wear glasses for poor night vision at the age 37 years. Molecular Genetics and Metabolism 69, 64 – 68 (2000) doi:10.1006/mgme.1999.2946, available online at http://www.idealibrary.com on 64 1096-7192/00 $35.00 Copyright © 2000 by Academic Press All rights of reproduction in any form reserved.