Abnormalities in Gastrointestinal Motility Are Associated With Diseases of Oxidative Phosphorylation in Children Denesh K. Chitkara, M.D., Samuel Nurko, M.D., John M. Shoffner, M.D., Timothy Buie, M.D., and Alejandro Flores, M.D. Division of Gastroenterology and Nutrition, Children’s Hospital, Division of Pediatric Gastroenterology and Nutrition, Massachusetts General Hospital, and Division of Pediatric Gastroenterology and Nutrition, Floating Hospital for Children, Boston, Massachusetts; and Horizon Molecular Medicine Laboratory, Department of Biology, Georgia State University, Norcross, Georgia OBJECTIVE: Disorders of the mitochondrial electron trans- port chain enzymes of oxidative phosphorylation (OX- PHOS) have neurologic, musculoskeletal, ophthalmologic, cardiac, and GI manifestations. Many adult and pediatric patients with disorders of OXPHOS have abnormalities in intestinal motility. The purpose of this study was to describe pediatric patients who initially presented with signs of GI dysmotility and were later evaluated and found to have a disorder of OXPHOS. METHODS: Data were collected on six patients, including initial GI and neurologic symptoms, histology of skeletal muscle biopsies, mitochondrial DNA mutational analysis, OXPHOS enzyme assay, upper GI barium imaging, tech- netium-99M liquid gastric emptying scan, upper GI endos- copy, esophageal manometry, and antroduodenal manome- try. RESULTS: All six children presented with symptoms of GI dysmotility within 2 wk of life. Patients later developed symptoms of neurologic disorders. All patients had abnor- malities in OXPHOS enzyme analysis. Muscle histology showed nonspecific changes with no ragged red fibers. Se- quencing of the mitochondrial DNA showed no recognized mutations. No patient had any evidence of intestinal ob- struction or malrotation by upper GI barium imaging. Four patients had delayed gastric emptying. Three patients had endoscopic and histologic evidence of esophagitis. All six had demonstrable neuropathic abnormalities by antroduo- denal manometry, including the following: nonpropagated antral bursts, absent migrating motor complexes, postpran- dial antral hypomotility, retrograde migrating motor com- plexes, and tonic contractions with the migrating motor complex. CONCLUSION: Abnormalities in GI motility may be an early presenting sign of disorders of OXPHOS in children. (Am J Gastroenterol 2003;98:871– 877. © 2003 by Am. Coll. of Gastroenterology) INTRODUCTION Disorders of the mitochondrial electron transport enzymes of oxidative phosphorylation (OXPHOS) affect the neuro- logic, musculoskeletal, ophthalmologic, and cardiac, as well as the GI system (1). A hallmark of these disorders is that they involve a number of seemingly unrelated organ sys- tems. The phenotypic expression of these disorders of OX- PHOS has been grouped into a number of syndromes, such as Kearns-Sayre syndrome (chronic progressive external ophthalmoplegia, atypical pigmentary retinopathy, ataxia, and heart block), MELAS syndrome (mitochondrial en- cephalomyopathy, lactic acidosis, and stroke-like episodes), MNGIE (mitochondrial neurogastrointestinal encephalomy- opathy), as well as others (2). Patients with MNGIE have GI dysmotility, peripheral neuropathy, ophthalmoparesis, and muscle biopsy shows histologic features of mitochondrial myopathy (ragged red fibers, abnormal mitochondria, in- creased succinate dehydrogenase stain on muscle fibers) (3). However, there are reports of patients with disorders of OXPHOS and intestinal dysmotility who do not meet the full criteria for MNGIE (4 – 8). Here, we report the clinical presentation and characteristics of six pediatric patients who were initially diagnosed with idiopathic intestinal dysmotil- ity and were later found to have disorders of OXPHOS but who did not have MNGIE syndrome. MATERIALS AND METHODS Patient History A retrospective chart review was conducted on six patients with a history of GI dysmotility who were later proven to have a disorder of OXPHOS. Information regarding the GI and neurologic symptoms, magnetic resonance imaging of the head, histology on skeletal muscle biopsy, workup for This study was supported by National Institute of Health training grant number T32 DK07471-19. THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 98, No. 4, 2003 © 2003 by Am. Coll. of Gastroenterology ISSN 0002-9270/03/$30.00 Published by Elsevier Science Inc. doi:10.1016/S0002-9270(03)00049-2