Growth Patterns in Patients with Mucopolysaccharidosis VII

Overview

Journal Mol Genet Metab Rep

Specialty Endocrinology

Date 2023 Jul 7

PMID 37415957

Authors

Adriana M Montano

Agnieszka Rozdzynska-Swiatkowska

Agnieszka Jurecka

Antonio Nino Ramirez

Lin Zhang

Deborah Marsden

Raymond Y Wang

Paul Harmatz

Affiliations

Soon will be listed here.

Abstract

Objective: This study assessed growth patterns in patients with mucopolysaccharidosis (MPS) VII before enzyme replacement therapy.

Methods: Height, weight, and body mass index (BMI) measurements and -scores from patients from three clinical studies were compared with those from CDC healthy population growth charts. Relationships with age/sex and history of non-immune hydrops fetalis (NIHF) were assessed by linear regression and ANOVA, respectively.

Results: Among 20 enrolled patients with MPS VII, height -scores were near normal until 1 year of age but declined thereafter, particularly among males. There was no consistent pattern in weight -score. BMI -scores were above normal and increased slightly with age among males and were slightly below normal among females. Male patients with a history of NIHF had greater declines in height and weight -scores over time versus males without history of NIHF. There was no clear effect of NIHF history on height and weight -scores in female patients.

Conclusions: In patients with MPS VII, declines in height -score began early in life, particularly among males, while changes in BMI varied by sex. Patients with MPS VII and a history of NIHF had greater declines in height -score with age than did patients without a history of NIHF. This retrospective analysis included patients enrolled in an open-label phase 2 study (UX003-CL203; ClinicalTrials.gov, NCT02418455), a randomized, placebo-controlled, blind-start phase 3 study (UX003-CL301; ClinicalTrials.gov, NCT02230566), or its open-label, long-term extension (UX003-CL202; ClinicalTrials.gov, NCT02432144). Requests for individual de-identified participant data and the clinical study report from this study are available to researchers providing a methodologically sound proposal that is in accordance with the Ultragenyx data sharing commitment. To gain access, data requestors will need to sign a data access and use agreement. Data will be shared via secured portal. The study protocol and statistical analysis plan for this study are available on the relevant clinical trial registry websites with the tabulated results.

References

Simonaro C . Cartilage and chondrocyte pathology in the mucopolysaccharidoses: The role of glycosaminoglycan-mediated inflammation. J Pediatr Rehabil Med. 2011; 3(2):85-8. DOI: 10.3233/PRM-2010-0120. View

Simonaro C, DAngelo M, He X, Eliyahu E, Shtraizent N, Haskins M . Mechanism of glycosaminoglycan-mediated bone and joint disease: implications for the mucopolysaccharidoses and other connective tissue diseases. Am J Pathol. 2007; 172(1):112-22. PMC: 2189614. DOI: 10.2353/ajpath.2008.070564. View

Kakkis E, Marsden D . Urinary glycosaminoglycans as a potential biomarker for evaluating treatment efficacy in subjects with mucopolysaccharidoses. Mol Genet Metab. 2020; 130(1):7-15. DOI: 10.1016/j.ymgme.2020.02.006. View

Peck S, Tobias J, Shore E, Malhotra N, Haskins M, Casal M . Molecular profiling of failed endochondral ossification in mucopolysaccharidosis VII. Bone. 2019; 128:115042. PMC: 6813906. DOI: 10.1016/j.bone.2019.115042. View

Viskochil D, Clarke L, Bay L, Keenan H, Muenzer J, Guffon N . Growth patterns for untreated individuals with MPS I: Report from the international MPS I registry. Am J Med Genet A. 2019; 179(12):2425-2432. PMC: 6899772. DOI: 10.1002/ajmg.a.61378. View

Smith L, Baldo G, Wu S, Liu Y, Whyte M, Giugliani R . Pathogenesis of lumbar spine disease in mucopolysaccharidosis VII. Mol Genet Metab. 2012; 107(1-2):153-60. PMC: 3428127. DOI: 10.1016/j.ymgme.2012.03.014. View

Montano A, Lock-Hock N, Steiner R, Graham B, Szlago M, Greenstein R . Clinical course of sly syndrome (mucopolysaccharidosis type VII). J Med Genet. 2016; 53(6):403-18. PMC: 4893087. DOI: 10.1136/jmedgenet-2015-103322. View

Sly W, Quinton B, McALISTER W, Rimoin D . Beta glucuronidase deficiency: report of clinical, radiologic, and biochemical features of a new mucopolysaccharidosis. J Pediatr. 1973; 82(2):249-57. DOI: 10.1016/s0022-3476(73)80162-3. View

Melbouci M, Mason R, Suzuki Y, Fukao T, Orii T, Tomatsu S . Growth impairment in mucopolysaccharidoses. Mol Genet Metab. 2018; 124(1):1-10. PMC: 5966322. DOI: 10.1016/j.ymgme.2018.03.004. View

10.

Smith L, Martin J, Szczesny S, Ponder K, Haskins M, Elliott D . Altered lumbar spine structure, biochemistry, and biomechanical properties in a canine model of mucopolysaccharidosis type VII. J Orthop Res. 2009; 28(5):616-22. PMC: 2975604. DOI: 10.1002/jor.21030. View

11.

Jiang Z, Derrick-Roberts A, Jackson M, Rossouw C, Pyragius C, Xian C . Delayed development of ossification centers in the tibia of prenatal and early postnatal MPS VII mice. Mol Genet Metab. 2018; 124(2):135-142. DOI: 10.1016/j.ymgme.2018.04.014. View

12.

Quartel A, Hendriksz C, Parini R, Graham S, Lin P, Harmatz P . Growth Charts for Individuals with Mucopolysaccharidosis VI (Maroteaux-Lamy Syndrome). JIMD Rep. 2014; 18:1-11. PMC: 4361922. DOI: 10.1007/8904_2014_333. View

13.

Simonaro C, DAngelo M, Haskins M, Schuchman E . Joint and bone disease in mucopolysaccharidoses VI and VII: identification of new therapeutic targets and biomarkers using animal models. Pediatr Res. 2005; 57(5 Pt 1):701-7. DOI: 10.1203/01.PDR.0000156510.96253.5A. View

14.

Tomatsu S, Orii K, Vogler C, Nakayama J, Levy B, Grubb J . Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease. Hum Mol Genet. 2003; 12(24):3349-58. DOI: 10.1093/hmg/ddg366. View

15.

Holtz M, Montano A, Sly W . Association between mucopolysaccharidosis Type VII and hydrops fetalis. Ultrasound Obstet Gynecol. 2019; 55(3):416-417. DOI: 10.1002/uog.20371. View

16.

Hinek A, Wilson S . Impaired elastogenesis in Hurler disease: dermatan sulfate accumulation linked to deficiency in elastin-binding protein and elastic fiber assembly. Am J Pathol. 2000; 156(3):925-38. PMC: 1876830. DOI: 10.1016/S0002-9440(10)64961-9. View

17.

Doherty C, Stapleton M, Piechnik M, Mason R, Mackenzie W, Yamaguchi S . Effect of enzyme replacement therapy on the growth of patients with Morquio A. J Hum Genet. 2019; 64(7):625-635. DOI: 10.1038/s10038-019-0604-6. View

18.

Tomatsu S, Montano A, Dung V, Grubb J, Sly W . Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat. 2009; 30(4):511-9. PMC: 3048808. DOI: 10.1002/humu.20828. View

19.

Patel P, Suzuki Y, Maeda M, Yasuda E, Shimada T, Orii K . Growth charts for patients with Hunter syndrome. Mol Genet Metab Rep. 2014; 1:5-18. PMC: 4060980. DOI: 10.1016/j.ymgmr.2013.10.001. View

20.

Vervoort R, Islam M, Sly W, Zabot M, Kleijer W, Chabas A . Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am J Hum Genet. 1996; 58(3):457-71. PMC: 1914559. View