[Frontiers in Bioscience, Landmark, 22, 385-406, January 1, 2016]

Mucopolysaccharidosis VI: Pathophysiology, diagnosis and treatment

Paul R. Harmatz 1 , Renee Shediac 2

1UCSF Benioff Children’s Hospital Oakland, Department of Gastroenterology, Oakland, CA, USA, 2BioMarin Pharmaceutical Inc., Novato, CA, USA

FIGURES
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Figure 1. Photograph of patients with MPS VI illustrating the phenotypic spectrum of the disease.

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Figure 2. Location of all the mucopolysaccharidosis VI (MPS VI) mutations in the human arylsulfatase B (ARSB) gene identified in a mutational analysis study by Karageorgos et al., 2007 (25) and predicted clinical severity associated with the mutations (represented by different colors) categorized on the basis of clinical criteria defined in the natural history study by Swiedler et al. (7). The boxes with Roman numerals represent exons of the gene. Reprinted with permission from Wiley and Sons.

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Figure 3. Radiographs of (A) the hands of a patient (16 years old, male) with MPS VI showing short, broad, and irregular metacarpals and phalanges and moderately severe Madelung deformity; and (B) hips from a patient with MPS VI (19 years old, male) showing bilateral hip dysplasia with flaring of iliac wings and flattening of the acetabulum bilaterally. There is also flattening and flaring of proximal femur with incomplete containment of the femoral heads.

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Figure 4. Association between urinary glycosaminoglycan (uGAG) levels and clinical outcomes in the MPS IV Survey study. Reprinted from Swiedler et al., 2005 (7), with permission from Wiley and Sons.

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Figure 5. Algorithm for the laboratory diagnosis of mucopolysaccharidosis VI (MPS VI). Reprinted from Wood et al., 2012 with permission from Elsevier (60).

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Figure 6. Impact of enzyme replacement therapy with galsulfase versus placebo on distance walked in a 12-minute walk test (12-MWT) in the phase 3 double-blind, 24-week clinical trial and 24-week open-label extension. Reprinted from Harmatz et al., 2006 with permission from Elsevier (69).

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Figure 7. Mean percent change in height and pulmonary function (forced vital capacity (FVC) and forced expiratory volume in one second (FEV1)) after onset of enzyme replacement therapy (ERT) by age group in the phase 1/2, 2 and 3 studies. Reprinted from Harmatz et al., 2010 with permission from Springer (84).