Abstract
Mucopolysaccharidosis type VI (MPS VI, Maroteaux-Lamy syndrome, MIM 253200) is an autosomal recessive lysosomal storage disease (LSD) caused by decreased activity of arylsulfatase B (N-acetylgalactosamine 4-sulfatase) enzyme resulting in dermatan sulfate accumulation; mucopolysaccharidosis type IVA (MPS IVA, Morquio syndrome A, MIM 253000) by decreased activity of N-acetylgalactosamine 6-sulfatase enzyme resulting in accumulation of keratan sulfate. Clinical symptoms include coarse facial features, joint stiffness, hepatosplenomegaly, hip osteonecrosis, and dysostosis multiplex. MPS IVA symptoms are similar but with joint hypermobility.
With suspicion of MPS disease, clinicians request urine studies for quantitative and qualitative glycosaminoglycans (GAGs). Diagnosis is confirmed by decreased enzyme activity in leukocytes or cultured skin fibroblasts. Further confirmation is obtained with identification of two mutations in the ARSB gene for MPS VI or mutations in the GALNS gene for MPS IVA.
We report slowly progressing patients, one with MPS VI and two with MPS IVA, who presented with skeletal changes and hip findings resembling Legg-Calvé-Perthes disease or spondyloepiphyseal dysplasia and normal/near normal urine GAG levels. The urine analysis data presented suggest that present screening techniques for MPS are inadequate in milder patients and result in delayed or missed diagnoses. The patients presented in this paper emphasize the importance of enzymatic and molecular testing.
Competing interests: None declared
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Communicated by: Eva Morava, MD PhD
Appendices
Take-Home Message
Attenuated MPS types VI and IVA may present with orthopedic concerns and normal or near normal quantitative GAG studies. A high index of clinical suspicion and careful enzyme analysis should be considered for early diagnosis.
Details of Contributions of Individual Authors
Nancy J. Mendelsohn, MD: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
Timothy Wood, PhD, FACMG: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
Rebecca A. Olson, RN, CNP, APNG: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
Renee Temme, MS, CGC: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
Susan Hale, MN, ARNP: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
Haoyue Zhang, PhD: Quantification of GAGs, interpretation of data, drafting and editing of manuscript
Lisa Read, MPH: Collection and interpretation of data, drafting and editing of manuscript
Klane K. White, MD, MSc: Study idea conception, collection and interpretation of data, drafting and editing of manuscript
All authors read and approved of the final manuscript.
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Nancy J. Mendelsohn, M.D.
Potential Conflict of Interest/Financial Disclosures
Nancy J. Mendelsohn received honorarium from BioMarin for travel, and receives grant funding from BioMarin. Tim Wood serves as a consultant for BioMarin. Klane White has received honoraria from BioMarin and Shire HGT, and receives grant funding from Biomarin.
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No outside funding was obtained for this case review.
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This case review did not require formal approval from an ethics committee as it did not incur any risk to the patients, and all information regarding the patients was de-identified.
Patient Consent Statement
Patient consent was not required for this study as it required only chart review and did not incur risk to the patients. All patient information was de-identified.
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Mendelsohn, N.J. et al. (2013). Spondyloepiphyseal Dysplasias and Bilateral Legg-Calvé-Perthes Disease: Diagnostic Considerations for Mucopolysaccharidoses. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 11. JIMD Reports, vol 11. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2013_231
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DOI: https://doi.org/10.1007/8904_2013_231
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