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In this session, Prof. Roberto Giugliani, a leading expert in medical genetics from Brazil, offers a comprehensive review of diagnostic strategies for mucopolysaccharidoses (MPS) using real-world case studies and diagnostic algorithms. The session emphasizes practical approaches for clinicians to identify and confirm MPS early, using both biochemical and molecular tools.
Prof. Giugliani begins by outlining classic clinical features of MPS: progressive symptoms in a child who appears normal at birth, joint stiffness, hepatosplenomegaly, dysostosis multiplex, corneal clouding, frequent ENT surgeries, and—in some types—cognitive decline. However, he cautions that similar signs may also appear in other lysosomal disorders like mucolipidosis, Niemann-Pick disease, or alpha-mannosidosis, reinforcing the need for laboratory confirmation.
A central message is that clinical suspicion is essential but insufficient. Diagnosis requires a stepwise process beginning with quantitative urinary glycosaminoglycan (GAG) analysis—preferably using age-adjusted reference values and avoiding unreliable qualitative tests. An elevated GAG level strengthens suspicion but does not confirm the diagnosis.
He details the interpretation of urinary GAG species (e.g., dermatan, heparan, keratan sulfates), which can help narrow the subtype of MPS. For example:
Enzyme assays follow to confirm the specific enzymatic deficiency. These can be done from leukocytes, plasma, or dried blood spots, though the latter is mainly a screening tool. Importantly, enzyme assays are highly reliable for confirming patient diagnoses but are not suitable for identifying carriers.
Molecular genetic analysis is critical for confirming diagnoses, identifying carriers, predicting phenotype severity, and enabling prenatal diagnosis. Prof. Giugliani explains how genotype–phenotype correlations can guide clinical expectations and treatment choices.
He concludes with a case of a 13-year-old boy diagnosed late with MPS II. The patient had early ENT surgeries, joint stiffness, and mild heart valve thickening but remained undiagnosed for years. Through the MPS Brazil Network, the team performed GAG analysis, enzyme testing, and genetic confirmation, leading to diagnosis and initiation of enzyme replacement therapy (ERT). While some symptoms improved, irreversible damage could not be reversed—underscoring the need for early intervention.
Prof. Giugliani’s message is clear: systematic suspicion, structured testing, and timely referral can significantly improve outcomes for MPS patients.