Development of a Clinical Algorithm for the Early Diagnosis of Mucopolysaccharidosis III

Maria Escolar,Nicole Muschol,Jessica Bradshaw,Lynn Golightly,Tessa Wirt,Charles Marques Lourenço,Tim Wood,Lonnie Zwaigenbaum,Valerie Tharp Byers,Jennifer Siedman,Kimberly Mcdonald,Roberto Giugliani,Martha L Solano,Imogen Newsom-Davis,Holly L Peay,Cara O’Neill

doi:10.1590/2326-4594-jiems-2020-0002

Abstract

Abstract Mucopolysaccharidosis III (MPS III) is a rare inherited metabolic disease primarily affecting the central nervous system, leading to developmental and/or speech regression. Early diagnosis of the disease is important to introduce appropriate management measures and to optimize therapeutic outcomes. The diagnosis of MPS III is often significantly delayed due to the rarity of the disease, the more attenuated somatic presentation compared to other MPS types, and the symptom overlap with other developmental disorders. To shorten the time to diagnosis, a list of eight early signs and symptoms was identified through an expert system approach by a global, multidisciplinary working group of 13 specialists with expertise in various aspects of MPS and developmental disorders and three parents of MPS III patients. Coarse facial features and persistent hirsutism or prominent, thick eyebrows were identified as the most important MPS III early signs. The list of eight early MPS III signs and symptoms is the first step towards the development of a clinical algorithm aiming to identify neonates and infants with MPS III before the onset of neurocognitive damage, ultimately shortening the diagnostic journey of MPS III patients.

Highlights

Mucopolysaccharidoses (MPSs) are a group of rare, autosomal recessive lysosomal storage disorders
Subtle behavioral differences supporting the differential diagnosis do exist and the autistic-like symptoms of Mucopolysaccharidosis III (MPS III) patients differ from those seen in children with autism spectrum disorder in several ways
New treatment options for the disease are being developed, neurocognitive deterioration will likely only be prevented if treatment is initiated before the onset of developmental delay

Summary

Introduction

Mucopolysaccharidoses (MPSs) are a group of rare, autosomal recessive lysosomal storage disorders. An expert system approach[22] was applied to select the most important early signs and symptoms that should be tested in an MPS III early diagnosis algorithm aiming at reducing the average diagnostic age of MPS III patients to less than 2 years. Part of the signs and symptoms that were identified, including behavioral problems, speech regression, coarse facial features, gastro-intestinal problems, mouthing, sensorineural hearing loss, hip dysplasia, and sleep disturbances, might only occur after the age of 1 year, especially in patients with a more slowly progressing disease.

Results

Conclusion