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| A devastating yet underdiagnosed disease |
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| Wide variability in the clinical presentation of MPS diseases creates a diagnostic challenge, and as a result, diagnosis is often delayed. In MPS I, a disease with similar clinical presentation, the average time from initial presentation to correct diagnosis is 2.5 years. Underdiagnosis is likely due to the rarity of the disease and the broad spectrum of clinical presentation. Different patients progress at widely varying rates, and initial symptoms may be the same as common pediatric complaints. MPS VI requires a high index of suspicion as early diagnosis may minimize irreversible damage. |
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| MPS VI progresses at different rates |
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| Multisystemic abnormalities reduce mobility and impair endurance |
| Because of the multisystemic and progressive nature of the disease, reduced endurance and mobility are common in more advanced patients. Due to abnormalities in the heart, lungs, joints, and bones, all patients eventually experience impaired endurance. |
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| Have you seen Maroteaux-Lamy? |
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| Diagnosis requires a high index of suspicion. |
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| MPS VI patients usually appear normal at birth. The heterogeneous clinical features may become apparent in infancy, childhood, adolescence, or early adulthood, depending on the rate of progression of the disease. Physical symptoms may vary widely depending on the individual, making early diagnosis difficult. Usually, the physicians involved in evaluating individuals prior to diagnosis of MPS VI are pediatricians and other pediatric specialists. |
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| When clinical manifestations suggest MPS VI, referral to a medical geneticist is warranted. Usually, further evaluation by the geneticist consists of a thorough medical history, physical examination, radiographic studies, and diagnostic laboratory tests. |
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| Elevated urinary glycosaminoglycan (GAG) is indicative of an MPS disorder; enzyme assay confirms diagnosis |
| When MPS is suspected, the geneticist may first perform a test to determine whether an excess amount of GAG is excreted in the urine. |
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| Urinary GAG excretion reflects the amount of lysosomal storage of GAG in the kidney tubules and is considered, by association, to be related to the overall storage of GAG in other tissues.3 It is not, however, the gold standard for diagnosis. Only a specific enzyme assay, which reveals the amount of ASB activity, can distinguish between MPS diseases and confirm MPS VI diagnosis. |
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| MPS VI is caused by a deficiency in arylsulfatase B |
| MPS VI is caused by an inherited deficiency in the lysosomal enzyme arylsulfatase B (ASB; also called N-acetylgalactosamine-4-sulfatase).10 Owing to the presence of different mutations in the gene in different MPS VI patients, heterogeneity exists in the nature of the deficiency in the enzyme.10 For example, the intracellular synthesis, maturation, stability, amount, specific activity, transport, or localization of ASB may be deficient. |
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| Degradation of dermatan sulfate by ASB |
| Glycosaminoglycans (GAGs; formerly called mucopolysaccharides) have important roles in cellular structure and cell interactions, particularly in connective tissue and its extracellular matrix.11 Arylsulfatase B (ASB) is 1 of 5 enzymes necessary for the stepwise degradation of the GAG dermatan sulfate in cell lysosomes, the organelles responsible for the breakdown of metabolites.1 |
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| GAG accumulation in MPS VI |
| GAG catabolism occurs within lysosomes, the cellular organelles responsible for the selective hydrolysis of molecular byproducts. Lysosomes deficient in ASB retain excess amounts of GAG. Replete with excess GAG, the lysosomes crowd the nucleus and other critical organelles, engorging the cell. This leads to cellular malfunction and multisystemic organ damage. |
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