Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux–Lamy Syndrome)

Abstract

Background: The skeletal phenotype of mucopolysaccharidosis VI (MPS VI) is characterized by short stature and growth failure.Objective: The purpose of this study was to construct reference growth curves for MPS VI patients with rapidly and slowly progressive disease.Methods: We pooled cross-sectional and longitudinal height for age data from galsulfase (Naglazyme ® , BioMarin Pharmaceutical Inc.), treatment naïve patients (n ¼ 269) who participated in various MPS VI studies, including galsulfase clinical trials and their extension programs, the MPS VI clinical surveillance program (CSP), and the MPS VI survey and resurvey studies, to construct growth charts for the MPS VI population. There were 229 patients included in this study, of which data from 207 patients 25 years of age with 513 height measurements were used for constructing reference growth curves.Results: Height for age growth curves for the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles were constructed for patients with rapidly and slowly progressing disease defined by the pre-enzyme replacement therapy (ERT) uGAG levels of > or 200 mg/mg creatinine. The mean (SD) pre-ERT uGAG levels were 481.0 (218.6) and 97.8 (56.3) mg/mg creatinine for the patients 25 years of age with rapidly (n ¼ 131) and slowly (n ¼ 76) progressing MPS VI disease, respectively. The median growth curves for patients with and >200 mg/mg creatinine were above and below the median (50th percentile) growth curve for the entire MPS VI population.Conclusion: MPS VI growth charts have been developed to assist in the clinical management of MPS VI patients.

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

“…Median body length for individuals with severe MPS I was slightly greater than the reference median in the first year. This is similar to observations in other MPS subtypes, including MPS II, MPS III, and MPS VI, where either normal growth or overgrowth is observed early in life in both severe and attenuated phenotypes (Montano et al, ; Muschol et al, ; Patel et al, ; Quartel et al, ; Rozdzynska‐Swiatkowska, Jurecka, Cieslik, & Tylki‐Szymanska, ; Tomatsu et al, ). Thus, short stature is not a common finding in the first 2 years of life for individuals with either severe or attenuated MPS I.…”

“…Disordered growth is a common manifestation of the mucopolysaccharidosis (MPS). Disease‐specific growth charts are available for several MPS disorders (Montano, Tomatsu, Brusius, Smith, & Orii, ; Patel et al, ; Quartel et al, ) but have not been developed for MPS I. Describing the natural history of growth patterns in MPS I could prove helpful in the evaluation of treatment impact and provide insights into disease pathogenesis for this condition.…”

Relationships among Height, Weight, Body Mass Index, and Age in Taiwanese Children with Different Types of Mucopolysaccharidoses

“…Knowledge about the natural history and growth pattern of MPS is important when assessing the therapeutic efficacy. Previous studies have described the growth pattern in MPS patients, however, these reports only focused on a specific type of MPS without comparing the results with other types of MPS in a single population [5,[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22]. The purpose of this study was to compare growth patterns among Taiwanese patients with different types of MPS.…”

Mucopolysaccharidosis VI pathophysiology diagnosis and treatment

“…Musculoskeletal disease can result in short stature (adult height below 120 cm in rapidly progressing patients), low body weight, nerve entrapment syndromes such as spinal cord compression, nerve root compression and carpal tunnel syndrome, and poor mobility (8,9). Patients with rapidly progressing MPS VI generally show normal to accelerated growth velocity during the first year of life, which slows down in the second year of life to below the fifth percentile of Centre for Disease Control (CDC) reference curves after the age of 3 years (10)(11)(12). Other common findings in these patients are coarse facial features with frontal bossing, depressed nasal bridge, enlarged tongue, gingival hypertrophy, teeth abnormalities, hirsutism, compromised pulmonary function, impaired vision (due to corneal clouding, high hyperopia, optic nerve injury, or retinopathy), impaired hearing, cardiac valve abnormalities, hepatosplenomegaly, and umbilical and inguinal hernias (6,7).…”

“…The slowly progressing phenotype of MPS VI is associated with a slower clinical course or with clinically significant symptoms occurring in fewer systems. Adult patients with this phenotype tend to have heights above 140 cm (6,7,12). They generally show normal or only mildly coarsened facial features, a slightly reduced to normal body height, and less prominent skeletal dysplasia compared to the rapidly progressing phenotype.…”