Growth patterns in patients with mucopolysaccharidosis VII - PubMed (original) (raw)

Growth patterns in patients with mucopolysaccharidosis VII

Adriana M Montaño et al. Mol Genet Metab Rep. 2023.

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 _Z_-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 _Z_-scores were near normal until 1 year of age but declined thereafter, particularly among males. There was no consistent pattern in weight _Z_-score. BMI _Z_-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 _Z_-scores over time versus males without history of NIHF. There was no clear effect of NIHF history on height and weight _Z_-scores in female patients.

Conclusions: In patients with MPS VII, declines in height _Z_-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 _Z_-score with age than did patients without a history of NIHF.Clinical trial registration: 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.

Keywords: Growth; Height; MPS VII; Weight, BMI.

© 2023 The Authors. Published by Elsevier Inc.

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Conflict of interest statement

Adriana M. Montaño has received research support from 10.13039/100013220Ultragenyx Pharmaceutical Inc. Agnieszka Różdżyńska-Świątkowska declares no conflicts of interest. Agnieszka Jurecka, Antonio Nino Ramirez, Lin Zhang, and Deborah Marsden are employees of and own stock in Ultragenyx Pharmaceutical Inc. Raymond Y. Wang has received research support from Ultragenyx Pharmaceutical Inc. Paul Harmatz has received research and consulting support from Ultragenyx Pharmaceutical Inc.

Figures

Fig. 1

Fig. 1

Change over time in height in patients with MPS VII compared with a healthy population. Height was assessed in male (A) and female (B) patients with MPS VII aged ≤36 months and all ages versus the height percentiles of the healthy population using the Centers for Disease Control and National Center for Health Statistics Clinical Growth Chart. Each data represents a single measurement; colors show measurements over time in a single patient.

Fig. 2

Fig. 2

Relationship of height and weight with age in patients with MPS VII. Linear regression analysis of height _Z_-score in male (A) and female (B) patients with MPS VII aged ≤12 months and > 12 months. Linear regression of weight Z-score in male (C) and female (D) patients with MPS VII aged ≤12 months and > 12 months.

Fig. 3

Fig. 3

Change over time in weight in patients with MPS VII compared with a healthy population. Weight was assessed in male (A) and female (B) patients with MPS VII aged ≤36 months and all ages versus the height percentiles of the healthy population using the Centers for Disease Control and National Center for Health Statistics Clinical Growth Chart. Each data represents a single measurement; colors show measurements over time in a single patient.

Fig. 4

Fig. 4

Effect of history of NIHF on the change over time in height in patients with MPS VII. Height was assessed in male (A) and female (B) patients with MPS VII aged ≤36 months and all ages versus the height percentiles of the healthy population using the Centers for Disease Control and National Center for Health Statistics Clinical Growth Chart. Each red dot represents a single height measurement in a patient with a history of NIHF; each blue dot represents a single height measurement in a patient without a history of NIHF. MPS, mucopolysaccharidosis; NIHF, non-immune hydrops fetalis.

Fig. 5

Fig. 5

Effect of history of NIHF on the change over time in weight in patients with MPS VII. Weight was assessed in male (A) and female (B) patients with MPS VII aged ≤36 months and all ages versus the height percentiles of the healthy population using the Centers for Disease Control and National Center for Health Statistics Clinical Growth Chart. Each red dot represents a single weight measurement in a patient with a history of NIHF; each blue dot represents a single weight measurement in a patient without a history of NIHF. MPS, mucopolysaccharidosis; NIHF, non-immune hydrops fetalis.

References

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Further reading

    1. Islam M.R., Vervoort R., Lissens W., Hoo J.J., Valentino L.A., Sly W.S. beta-Glucuronidase P408S, P415L mutations: evidence that both mutations combine to produce an MPS VII allele in certain Mexican patients. Hum. Genet. 1996;98:281–284. -PubMed
    1. Tomatsu S., Montaño A.M., Dung V.C., Grubb J.H., Sly W.S. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly syndrome) Hum. Mutat. 2009 Apr;30(4):511–519. -PMC -PubMed
    1. Vervoort R., Islam M.R., Sly W.S., Zabot M.T., Kleijer W.J., Chabas A., Fensom A., Young E.P., Liebaers I., Lissens W. Molecular analysis of patients with beta-glucuronidase deficiency presenting as hydrops fetalis or as early mucopolysaccharidosis VII. Am. J. Hum. Genet. 1996 Mar;58(3):457–471. -PMC -PubMed

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