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Cardiovascular Histopathology of a 11-Year Old with Mucopolysaccharidosis VII Demonstrates Fibrosis, Macrophage Infiltration, and Arterial Luminal Stenosis

  • Valerie Lew
  • Louis Pena
  • Robert Edwards
  • Raymond Y. Wang
Research Report
Part of the JIMD Reports book series (JIMD, volume 39)

Abstract

Mucopolysaccharidosis type VII (MPS VII) is caused by β-glucuronidase deficiency, resulting in lysosomal accumulation of glycosaminoglycans (GAGs) and multisystemic disease. We present cardiovascular gross and histopathology findings from a 11-year-old MPS VII male, who expired after developing ventricular fibrillation following anesthesia induction. Gross anatomic observations were made at autopsy; postmortem formalin-fixed paraffin-embedded samples of the carotid artery, aorta, myocardium, and valves were sectioned and stained with hematoxylin-eosin, Verhoeff-Van Gieson, CD68, and trichrome stains. Gross heart findings include an enlarged, dilated heart, mitral valve prolapse with thick, shortened chordae tendinae, and thickened aortic valve cusps. The aorta contained raised intimal plaques mimicking conventional atherosclerosis. Cardiac myocytes included hypertrophic nuclei, subendocardial fibrosis, and increased interfascicular collagen. Coronary lumens were 40–70% stenosed by fibrointimal hyperplasia containing storage material-laden cells, CD68+ macrophages, and fragmented elastin laminae. Similar findings were visualized in aortic intimal plaques. We confirm that arterial plaques, elastin fragmentation, and activated CD68+ macrophage infiltration occur in human MPS VII, consistent with previously observed findings in murine and canine MPS VII. We also confirm ultrasonographically observed carotid intimal-medial thickening is an in vivo correlate of histopathologic vascular fibrointimal hyperplasia. MPS VII patients should be regularly monitored for cardiac disease, with methods such as Holter monitors and stress testing; MPS VII-directed treatments should effectively address cardiovascular disease.

Keywords

Cardiovascular Histopathology Mucopolysaccharidosis VII Outcome Postmortem Sly syndrome 

Notes

Acknowledgments

The authors are grateful to the patient’s parents for consenting to autopsy, and to Long Beach Memorial Hospital for obtaining autopsy consent. The authors are also grateful to the Los Angeles County Coroner’s Office (Dan Anderson, Dr. Jason Tovar, Dr. Christopher Rogers, and Dr. Kevin Miller), and to Dr. Lisa Shane of Long Beach Miller Children’s Hospital, for their efforts to make this publication possible. RYW is supported by the CHOC Children’s Specialists Tithe Grant and the Brian and Caris Chan Family Foundation. The findings and conclusions in this chapter are those of the authors, and do not necessarily represent the official position of the County of Los Angeles or the Los Angeles County Department of the Medical Examiner-Coroner.

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Copyright information

© SSIEM and Springer-Verlag Berlin Heidelberg 2017

Authors and Affiliations

  • Valerie Lew
    • 1
  • Louis Pena
    • 2
    • 3
  • Robert Edwards
    • 4
  • Raymond Y. Wang
    • 5
    • 6
  1. 1.UC Riverside School of MedicineRiversideUSA
  2. 2.Los Angeles County Department of Medical Examiner-CoronerLos AngelesUSA
  3. 3.Hidalgo Medical ServicesLordsburgUSA
  4. 4.Department of Pathology & Lab MedicineUniversity of California, Irvine School of MedicineOrangeUSA
  5. 5.Department of PediatricsUniversity of California, Irvine School of MedicineOrangeUSA
  6. 6.Division of Metabolic DisordersChildren’s Hospital of Orange CountyOrangeUSA

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