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MPS Reference
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MPS VII: an overview

Patients with mucopolysaccharidosis (MPS VII) are at elevated risk for severe morbidity and early mortality1

MPS VII, also known as Sly syndrome, is a progressive, multisystemic disease caused by a deficiency of the enzyme β-glucuronidase, which is required for the degradation of the glycosaminoglycans (GAGs) heparan sulfate, dermatan sulfate and chondroitin sulfate.1
MPS VII can present as early as birth with hydropsis fetalis, or as a young child or adolescent with delayed motor development, mild to severe cognitive impairment and multi-organ disease.1-4

Observed presentation

  • Symptoms appear at varying ages, depending on rate of disease progression:
    • Rapidly progressing, birth1
    • Slowly progressing, late infancy to adolescence1-3
  • Observed presentation includes the following 1,2,4,5:
    • Coarse facial features
    • Hepatosplenomegaly
    • Gibbus deformity
    • Diastasis recti
    • Hernia
    • Short stature
    • Cognitive impairment
    • Frequent respiratory infections
    • Mild to moderate dysostosis multiplex
    • Corneal clouding
    • Hearing loss
    • Speech loss
    • Cardiac valve abnormalities
  • Specific recommendations for consideration of MPS VII include the following:
    • Infants presenting with hydrops fetalis at birth should be considered.1,4
    • In reported cases, coarse facial features, developmental delay, hepatosplenomegaly and cardiac valve abnormalities prompted testing.2,5,6

Disease progression

  • Overall disease burden:
    • Patients experience multi-organ dysfunction and possibly cognitive decline, with a resulting high disease burden.2-5
    • Patients can lose their ability to independently ambulate, communicate and care for themselves, thereby increasing caregiver needs.4,6,7
  • Rapidly progressing patients:
    • Disease presents at birth with hydrops fetalis and severe cognitive impairment.1
    • Patients have been reported to die early in life, within a year of birth, due to hydrops fetalis.1
  • Slowly progressing patients:
    • Disease presents with coarse facial features, developmental delay, hepatosplenomegaly and cardiac valve abnormalities.2,4
    • As the disease progresses, patients can also experience cognitive decline, loss of ambulation, loss of ability to take care of themselves, and loss of ability to communicate.4,6,7
    • Patients can survive into their 50s; death has been reported to be associated with cardiac or pulmonary failure.1,4,7
  • There is no conclusive information on the most frequent types of surgeries patients with MPS VII undergo, but the following have been detailed in case reports4,5,7:
    • Tracheostomy
    • Scoliosis repair surgery
    • Surgical repair of the mitral valve
    • Cervical fusion
  • Because patients with MPS often experience anaesthetic complications due to obstructed airways, care must be taken for patients undergoing surgery.8

Genetic information

  • MPS VII is caused by mutations in the β-glucuronidase gene, GUSB.1
  • There are 27 known pathogenic variants within GUSB.9
  • Mutations in GUSB and resulting enzyme deficiency leads to accumulation of the GAGs heparan sulfate, dermatan sulfate and chondroitin sulfate.1

Key management considerations

  • There are currently no approved therapies for MPS VII; new approaches for the treatment of MPS VII are under clinical investigation.
  • Available treatment and management recommendations:
    • Bernsen PLJA, Wevers RA, Gabreëls FJM, Lamers KJB, Sonnen AEH, Schuurmans Stekhoven JH Phenotypic expression in mucopolysaccharidosis VII. J Neurol Neurosurg Psychiatry. 1987;50(6):699-703.
    • Gniadek TJ, Singer N, Barker NJ, et al. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome). Cardiovasc Pathol. 2015;24(5):322-326. doi:10.1016/j.carpath.2015.06.001.
    • Tomatsu S, Montaño AM, Dung VC, Grubb JH, Sly WS. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat. 2009;30(4):511-519. doi:10.1002/humu.20828.
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References:  1. Tomatsu S, Montaño AM, Dung VC, Grubb JH, Sly WS. Mutations and polymorphisms in GUSB gene in mucopolysaccharidosis VII (Sly Syndrome). Hum Mutat. 2009;30(4):511-519. doi:10.1002/humu.20828.  2. Gehler J, Cantz M, Tolksdorf M, Spranger J, Gilbert E, Drube H. Mucopolysaccharidosis VII: β-glucuronidase deficiency. Humangenetik. 1974;23(2):149-158.  3. Bernsen PLJA, Wevers RA, Gabreëls FJM, Lamers KJB, Sonnen AEH, Schuurmans Stekhoven JH Phenotypic expression in mucopolysaccharidosis VII. J Neurol Neurosurg Psychiatry. 1987;50(6):699-703.  4. Gniadek TJ, Singer N, Barker NJ, et al. Cardiovascular pathologies in mucopolysaccharidosis type VII (Sly Syndrome). Cardiovasc Pathol. 2015;24(5):322-326. doi:10.1016/j.carpath.2015.06.001.  5. Nampoothiri S, Mahesh K, Hiran KR, Sunitha V. Sly disease: mucopolysaccharidosis type VII. Indian Pediatr. 2008;45(10):859-861.  6. Yamada Y, Kato K, Sukegawa K, et al. Treatment of MPS VII (Sly disease) by allogeneic BMT in a female with homozygous A619V mutation. Bone Marrow Transplant. 1998;21(6):629-634.  7. Fox JE, Volpe L, Bullaro J, Kakkis ED, Sly WS. First human treatment with investigational rhGUS enzyme replacement therapy in an advanced stage MPS VII patient. Mol Genet Metab. 2015;114(2):203-208. doi:10.1016/j.ymgme.2014.10.017.  8. Muenzer J, Beck M, Eng CM, et al. Long-term, open-labeled extension study of idursulfase in the treatment of Hunter syndrome Genet Med. 2011;13(2):95-101. doi:10.1097/GIM.0b013e3181fea459.  9. Online Mendelian Inheritance in Man, OMIM. Baltimore, MD: Johns Hopkins University Press. http://www.ncbi.nlm.nih.gov/omim. Updated December 20, 2015. Accessed December 21, 2015.