AIM: The aim of this study was to develop an algorithm to prompt early clinical suspicion of mucopolysaccharidosis type I (MPS I). METHODS: An international working group was established in 2016 that comprised 11 experts in paediatrics, rare diseases and inherited metabolic diseases. They reviewed real-world clinical cases, selected key signs or symptoms based on their prevalence and specificity and reached consensus about the algorithm. The algorithm was retrospectively tested. RESULTS: An algorithm was developed. In patients under two years of age, kyphosis or gibbus deformity were the key symptoms that raised clinical suspicion of MPS I and in those over two years they were kyphosis or gibbus deformity, or joint stiffness or contractures without inflammation. The algorithm was tested on 35 cases, comprising 16 Hurler, 10 Hurler-Scheie, and nine Scheie patients. Of these 35 cases, 32 (91%) - 16 Hurler, nine Hurler-Scheie and seven Scheie patients - would have been referred earlier if the algorithm had been used. CONCLUSION: The expert panel developed and tested an algorithm that helps raise clinical suspicion of MPS I and would lead to a more prompt final diagnosis and allow earlier treatment.

Center for Rare Diseases Clinic for Paediatric and Adolescent Medicine HELIOS Dr Horst Schmidt Kliniken Wiesbaden Wiesbaden Germany

Centre for Inherited Metabolic Diseases Departments of Paediatrics and Clinical Genetics Copenhagen University Hospital Rigshospitalet Copenhagen Denmark

Department of Paediatric Neurology and Metabolic Diseases Brussels Belgium

Department of Paediatrics Academic Medical Center Amsterdam The Netherlands

Department of Pediatrics and Adolescent Medicine 1st Faculty of Medicine Charles University and General University Hospital Prague Czech Republic

Department of Pediatrics Nutrition and Metabolic Diseases The Children's Memorial Health Institute Warsaw Poland

Department of Pediatrics University of Padova Padova Italy

Division of Child Neurology Department of Pediatrics Mafraq Hospital Bani Yas Abu Dhabi United Arab Emirates

Rare Metabolic Diseases Unit Paediatric Clinic Fondazione MBBM San Gerardo University Hospital Monza Italy

Reference Centre of Metabolic Diseases Hôpital Femme Mère Enfant Bron France

Unit of Rare Diseases Department of Paediatrics IRCCS Giannina Gaslini Genova Italy

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