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Jan D. Marshall, BA; Roderick T. Bronson, DVM; Gayle B. Collin, MS; Anne D. Nordstrom, PhD; Pietro Maffei, MD, PhD; Richard B. Paisey, MD; Catherine Carey, MD; Seamus MacDermott, MD; Isabelle Russell-Eggitt, MD; Sarah E. Shea, MD; Judy Davis, MD; Sebastian Beck, MD, PhD; Gocha Shatirishvili, MD; Cristina Maria Mihai, MD; Maria Hoeltzenbein, MD; Giovanni Battista Pozzan, MD; Ian Hopkinson, MD, PhD; Nicola Sicolo, MD; Jürgen K. Naggert, PhD; Patsy M. Nishina, PhD

Arch Intern Med. 2005;165:675-683.

Background  Alström syndrome is a recessively inherited genetic disorder characterized by congenital retinal dystrophy that leads to blindness, hearing impairment, childhood obesity, insulin resistance, and type 2 diabetes mellitus. We provide new details on cardiologic, hepatic, gastrointestinal, urologic, pulmonary, and neurobehavioral phenotypes in Alström syndrome and describe the histopathologic findings in 5 individuals.

Methods  We obtained data on 182 patients from clinical examinations, medical record reviews, standardized questionnaires, and personal interviews with physicians and parents.

Results  Dilated cardiomyopathy occurred in 60% of patients. Age at onset was either during infancy, often before vision disturbances were noted, or in adolescence or adulthood. There is a risk of recurrence of infantile cardiomyopathy. Hyperinsulinemia (92%) developed in early childhood and progressed to type 2 diabetes mellitus in 82% of those older than 16 years. Hypertriglyceridemia (54%) precipitated pancreatitis in 8 patients. Urologic dysfunction and gastrointestinal disturbances occurred in 48% and 35% of patients, respectively. Fifty-three percent of patients had persistent pulmonary symptoms. Neurologic symptoms in 20% of patients included clonic tic and absence seizures. Developmental motor or language delays were observed in 46% of patients. Fibrotic infiltrations of multiple organs, that is, kidney, heart, liver, lung, urinary bladder, gonads, and pancreas, were observed.

Conclusions  The wide-ranging and complex spectrum of phenotypes reported herein broadens those previously described for Alström syndrome. These findings will aid physicians in making an early and accurate diagnosis and will help effect appropriate monitoring and treatment.

Author Affiliations: The Jackson Laboratory, Bar Harbor, Me (Mss Marshall and Collin and Drs Bronson, Naggert, and Nishina); Department of Sociology, University of New Hampshire, Durham (Dr Nordstrom); University School of Medicine, Padua, Italy (Drs Maffei, Pozzan, and Sicolo) Torbay Hospital, Torquay, England (Drs Paisey, Carey, and MacDermott); Department of Paediatric Ophthalmology, Great Ormond Street Hospital, London, England (Dr Russell-Eggitt); Department of Developmental Pediatrics, Izaak Walton Killam Health Centre, Halifax, Nova Scotia (Dr Shea); California Digestive Disease Center, Fresno (Dr Davis); Laboratório Biologia Molecular, Centro Genética Clínica, Porto, Portugal (Dr Beck); Program for Rare Diseases, Ministry of Labour, Health and Social Affairs of Georgia, Tbilisi (Dr Shatirishvili); Clinica de Pediatrie, Compartimentul de Diabet, Nutritie si Boli de Metabolism, Spitalul Clinic de Urgenta, Constanta, Romania (Dr Mihai); Max Planck Institute for Molecular Genetics, Berlin, Germany (Dr Hoeltzenbein); Department of Primary Care and Population Sciences, Royal Free University College Medical School, Whittington Campus, London, England (Dr Hopkinson); and Cardiovascular Genetics Unit, Department of Medicine, The Rayne Institute, University College London (Dr Hopkinson).

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