Growth patterns for untreated individuals with MPS I: Report from the international MPS I registry.

Abstract

Mucopolysaccharidosis Type I (MPS I), caused by deficiency of α‐L‐iduronidase results in progressive, multisystemic disease with a broad phenotypic spectrum including patients with severe (Hurler syndrome) to attenuated (Hurler–Scheie and Scheie syndromes) disease. Disordered growth is common with either phenotype. The study objectives were to construct sex‐ and age‐specific estimated length/height and head circumference growth curves for untreated individuals with severe and attenuated disease and compare them with clinical reference standards. Untreated individuals in the MPS I Registry with at least one observation for length/height and/or head circumference and assigned phenotype as of May 2017 were included. Median growth for 463 untreated individuals with severe disease deviated from reference growth curves by ~6 months of age and fell below the third percentile by 4 years of age. Median head circumference was above reference curves from 3 to 4 months through 3 years of age. Among 207 individuals with untreated attenuated disease, median height fell below the third percentile by 9 years of age with divergence from reference curves by 2 years of age. MPS I‐specific growth curves will be useful in evaluation of long‐term outcomes of therapeutics interventions and will provide a foundation for understanding the pathogenesis of skeletal disease in MPS I.