AIM: Mucopolysaccharidosis type I is a lysosomal storage disorder that can result in significant disease burden, disability and premature death, if left untreated. The aim of this review was to elaborate on the diagnosis of mucopolysaccharidosis type I and the pros and cons of newborn screening. METHODS: An international working group was established to discuss ways to improve the early diagnosis of mucopolysaccharidosis type I. It consisted of 13 experts in paediatrics, rare diseases and inherited metabolic diseases from Europe and the Middle East. RESULTS: It is becoming increasingly clearer that the delay between symptom onset and clinical diagnosis is considerable for mucopolysaccharidosis type I and other rare lysosomal storage disorders, despite numerous awareness campaigns since therapies became available. Diagnosis currently depends on recognising the signs and symptoms of the disease. The practice of newborn screening, which is being explored by pilot programmes around the world, enables early diagnosis and consequently early treatment. However, these studies have highlighted numerous new problems and pitfalls that must be faced before newborn screening becomes generally available. CONCLUSION: Newborn screening for mucopolysaccharidosis type I offers the potential for early diagnosis and early pre-symptomatic treatment, but existing hurdles need to be overcome.

Centre for Inherited Metabolic Diseases Department of Clinical Genetics Rigshospitalet Copenhagen University Hospital Copenhagen Denmark

Children's Hospital University Medical Center Johannes Gutenberg University Mainz Germany

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

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

Department of Pediatric Neurology and Metabolic Diseases UZ Brussel Brussels Belgium

Department of Pediatrics University of Padova Padova Italy

Division of Paediatric Neurology Department of Paediatrics Mafraq Hospital Abu Dhabi UAE

Metabolic Unit Great Ormond Street Hospital NHS Trust London UK

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

Reference Centre of Metabolic Diseases HFME Hospital Bron France

TIGET Institute IRCCS San Raffaele Hospital Milano Italy

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

Willink Biochemical Genetics Unit Manchester Centre for Genomic Medicine St Mary's Hospital Central Manchester Foundation Trust Manchester UK

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