A Step-By-Step Approach To Early Signs Of Mucopolysaccharidoses (MPS)

Prof. Scarpa begins by highlighting the rarity of MPS and its inclusion among lysosomal storage disorders (LSDs). While individually rare, MPS diseases collectively affect millions worldwide. He notes that delayed diagnosis is common—averaging 5 to 7 years—and often involves multiple misdiagnoses and inappropriate treatments before the correct one is reached. The consequences of late diagnosis include irreversible organ damage, poor quality of life, and premature mortality.

He uses compelling case examples to illustrate how early signs, such as joint stiffness, hernias, and ENT complications, are often misattributed to more common conditions like juvenile arthritis or skeletal dysplasia. One patient lived for over 50 years with undiagnosed MPS I, treated for rheumatoid arthritis until the correct diagnosis came too late for full therapeutic benefit.

Prof. Scarpa then transitions into a detailed explanation of the pathophysiology of MPS. He describes how enzymatic deficiencies lead to glycosaminoglycan (GAG) accumulation within lysosomes, initiating a cascade of events including inflammation, autophagy impairment, and progressive organ dysfunction. Importantly, he notes that CNS involvement occurs in 70–80% of patients, even though GAG storage in the brain may appear minimal under microscopy. This reinforces the concept that the pathological effects of MPS extend far beyond simple storage—disrupting cellular homeostasis, protein clearance, and mitochondrial function.

He explains that MPS types share many overlapping features, such as dysostosis multiplex, ENT manifestations, cardiac valve disease, and CNS decline, but that their clinical spectra can vary widely—from severe neuropathic forms to milder, somatic-only phenotypes.

Prof. Scarpa emphasizes the importance of newborn screening and early intervention. He outlines an ideal diagnostic pathway combining urinary GAG testing, enzyme assays, and next-generation sequencing. He also stresses the importance of multidisciplinary care, including orthopedic, cardiac, ENT, metabolic, and genetic specialists.

In conclusion, he underscores the urgent need for earlier diagnosis and proactive management, stating that with timely therapy, the cascade of damage can be significantly slowed or even halted—dramatically improving patient outcomes.