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.

Mucopolysaccharidosis Type I: A Review of the Natural History and Molecular Pathology

“…Skeletal disease in MPS I, collectively described as dysostosis multiplex, is one of the most prevalent and incapacitating manifestations [ 76 ] and is less likely to be modified by current therapies [ 77 , 78 , 79 ]. Most evident are stunted growth and thoracolumbar kyphosis [ 76 , 80 , 81 ]. Other abnormalities include flattened vertebral bodies, odontoid hypoplasia at cervical vertebra C2, oar-shaped ribs, short and thickened clavicles, bullet-shaped phalanges, a large skull with a thickened calvarium, and J-shaped sella turcica [ 82 ].…”

Intravenous Enzyme Replacement Therapy in Mucopolysaccharidoses: Clinical Effectiveness and Limitations

“…All types of MPSs experience abnormal growth with increased length at birth and decline of growth velocity beginning from 1 to 5-6 years of age [99,101,165,[169][170][171][172][173]. A complete or partial lack of pubertal growth spurt is also common in all MPS types [99,101,106,169,171,174]. In the first years of life, short height is more pronounced in MPS IVA, MPS I and MPS VI, but the final height is always shorter than healthy individuals in all MPSs, even in MPS III, the least affected type for growth [171].…”

“Growth patterns in children with mucopolysaccharidosis type I-Hurler after hematopoietic stem cell transplantation: Comparison with untreated patients”

“…In addition, auxological data collected between 9.0 and 9.99 years of age were recorded in those patients who had already achieved this age at the time of enrollment. This timepoint (t 9yrs ) was included in order to provide a longer-lasting comparison with the published centiles for untreated MPS-IH, that include patients as old as 10 years [ 24 ]. Height values recorded at older age could only be compared with the centiles for the general population but not with affected untreated patients.…”

“…In order to quantify the height gain in transplanted patients after HSCT compared to untreated ones, we also expressed all the auxological data recorded before the age of 10.0 years as SDS with reference to the centiles of untreated children published by Viskochil and colleagues [ 24 ].…”

“…However, MPS-IH growth curves after successful HSCT have never been compared to curves of untreated patients. Viskochil and colleagues have recently published the growth curves of untreated MPS-I patients, using data obtained from the MPS-I Registry [ 24 ]. Disease-specific growth charts were constructed on the basis of the auxological data available for 463 untreated individuals affected with MPS-IH.…”