Resolution of Elevated Urine Glycosaminoglycans and Clinical Features of Mucopolysaccharidosis After Successful Treatment of Neuroblastoma Megan V. Hilgers, MD,* Chester B. Whitley, PhD, MD,w and Christopher L. Moertel, MDz Summary: We report a patient with stage 3 ganglioneuroblastoma who initially presented with clinical and laboratory features con- sistent with mucopolysaccharidosis including coarse facial features, developmental delay, and an elevated quantitative urine glyco- saminoglycan (GAG) level. All mucopolysaccharidosis features resolved following successful treatment of neuroblastoma. High GAG levels have been documented in the pediatric oncology lit- erature, yet not as a potential marker of malignancy or other target for clinical utility. This patient prompts further investigation into the relationship between neuroblastoma and elevated GAG levels. Key Words: neuroblastoma, glycosaminoglycans, mucopolysa- ccharidosis (J Pediatr Hematol Oncol 2016;00:000–000) N euroblastoma is a malignant tumor derived from immature cells of the sympathetic nervous system and is most often diagnosed in children younger than 5 years of age. 1–4 Clinical presentation may consist of constitutional symptoms including fever, fatigue, weight loss or diarrhea, in addition to symptoms related to the tumor location such as abdominal distention, difficulty breathing, or bone pain. Treatment of neuroblastoma is based on risk stratification and may include chemotherapy, surgery, radiation, immu- notherapy, myeloablative therapy with autologous bone marrow transplantation, administration of 13-cis retinoic acid or use of radioactive iodine with methyl- iodobenzylguanine therapy. 2–5 Neuroblastoma outcomes, dependent on stage and histology, range from spontaneous regression to aggressive metastasis and death. 1,2,4,5 Mucopolysaccharidoses (MPSs) are inherited meta- bolic disorders caused by absence or dysfunction of lyso- somal enzymes responsible for the catabolism of glyco- saminoglycans (GAGs). 6 Accumulation of GAGs disrupts cellular functioning in multiple organ systems leading to the phenotypic heterogeneity of MPS. 6,7 Excess GAGs are excreted in urine, thus quantification of urinary GAGs is the initial diagnostic step for MPS while leukocyte enzyme assays and genetic mutation analyses are confirmatory. 6 MPS Type I, including Hurler and Scheie syndromes, is caused by absent or defective a-L-iduronidase and leads to accumulation of dermatan sulfate and heparan sulfate. 6,8,9 MPS I is typically diagnosed toward the end of the first year of life as patients progressively develop characteristic coarse facial features, corneal clouding, skeletal dysplasia, cardiac disease, hernias, hepatosplenomegaly, and/or devel- opmental delay. 6,8,9 Treatment options for MPS I include enzyme replacement therapy and hematopoietic stem cell transplantation. 8,9 Early intervention leads to improved outcomes and may preserve intellectual development. 8,9 We report a patient with ganglioneuroblastoma who presented with clinical and laboratory features of MPS I that resolved after successful treatment with chemotherapy and tumor debulking. This patient prompts inquiry into the correlation between neuroblastoma, urinary GAGs, and a MPS-like clinical picture. FIGURE 1. Photograph of the patient on presentation. Institu- tional Review Board approval and parental written consent were obtained for inclusion of this photograph. Received for publication August 17, 2015; accepted March 27, 2016. From the *Department of Pediatrics; wDepartment of Pediatrics, Division of Pediatric Genetics and Metabolism; and zDepartment of Pediatrics, Division of Pediatric Hematology and Oncology, Uni- versity of Minnesota Masonic Children’s Hospital, Minneapolis, MN. The authors declare no conflict of interest. Reprints: Christopher L. Moertel, MD, Division of Pediatric Hema- tology and Oncology, University of Minnesota, MMC 484 Mayo Building, 420 Delaware St. SE, Minneapolis, MN 55455 (e-mail: moert001@umn.edu). Copyright r 2016 Wolters Kluwer Health, Inc. All rights reserved. CLINICAL AND LABORATORY OBSERVATIONS J Pediatr Hematol Oncol  Volume 00, Number 00, ’’ 2016 www.jpho-online.com | 1 Copyright r 2016 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.