Early report EARLY REPORT lleal-lymphoid-nodular hyperplasia, non-specific colitis, and pervasive developmental disorder in children A J Wakefield, S H Murch, A Anthony, J Linnell, D M Casson, M Malik, M Berelowitz, A P Dhillon, M A Thomson, P Harvey, A Valentine, S E Davies, J A Walker-Smith Summary Background We investigated a consecutive series of children with chronic enterocolitis and regressive developmental disorder. Methods 12 children (mean age 6 years [range 3-10], 11 boys) were referred to a paediatric gastroenterology unit with a history of normal development followed by loss of acquired skills, including language, together with diarrhoea and abdominal pain. Children underwent gastroenterological, neurological, and developmental assessment and review of developmental records. lleocolonoscopy and biopsy sampling, magnetic-resonance imaging (MRI), electroencephalography (EEG), and lumbar puncture were done under sedation. Barium follow-through radiography was done where possible. Biochemical, haematological, and immunological profiles were examined. Findings Onset of behavioural symptoms was associated, by the parents, with measles, mumps, and rubella vaccination in eight of the 12 children, with measles infection in one child, and otitis media in another. All 12 children had intestinal abnormalities, ranging from lymphoid nodular hyperplasia to aphthoid ulceration. Histology showed patchy chronic inflammation in the colon in 11 children and reactive ileal lymphoid hyperplasia in seven, but no granulomas. Behavioural disorders included autism (nine), disintegrative psychosis (one), and possible postviral or vaccinal encephalitis (two). There were no focal neurological abnormalities and MRI and EEG tests were normal. Abnormal laboratory results were significantly raised urinary methylmalonic acid compared with age- matched controls (p=0.003), low haemoglobin in four children, and a low serum IgA in four children. Interpretation We identified associated gastrointestinal disease and developmental regression in a group of previously normal children, which was generally associated in time with possible environmental triggers. Lancet 1998; 351: 637-41 See Commentary page 611 Inflammatory Bowel Disease Study Group, University Departments of Medicine and Histopathology (A J Wakefield FRCS, A Anthony MB, J Linnell PhD, A P Dhillon MRCPath, S E Davies MRCPath) and the University Departments of Paediatric Gastroenterology (S H Murch MB, D M Casson MRCP, M Malik MRCP, M A Thomson FRCP, J A Walker-Smith FRCP,), Child and Adolescent Psychiatry (M Berelowitz FRCPsych), Neurology (P Harvey FRCP), and Radiology (A Valentine FRCR), Royal Free Hospital and School of Medicine, London NW3 2QG, UK Correspondence to: Dr A J Wakefield Introduction We saw several children who, after a period of apparent normality, lost acquired skills, including communication. They all had gastrointestinal symptoms, including abdominal pain, diarrhoea, and bloating and, in some cases, food intolerance. We describe the clinical findings, and gastrointestinal features of these children. Patients and methods 12 children, consecutively referred to the department of paediatric gastroenterology with a history of a pervasive developmental disorder with loss of acquired skills and intestinal symptoms (diarrhoea, abdominal pain, bloating and food intolerance), were investigated. All children were admitted to the ward for 1 week, accompanied by their parents. Clinical investigations We took histories, including details of immunisations and exposure to infectious diseases,