Mucopolysaccharidosis Type I - Hurler/Scheie And In Between

Prof. Gerit-Kircher begins by explaining the biochemical basis of MPS I. The disorder is caused by a deficiency in the enzyme alpha-L-iduronidase, which is essential for breaking down dermatan and heparan sulfate. The resulting accumulation of glycosaminoglycans (GAGs) leads to progressive tissue damage affecting multiple systems. She provides clear illustrations of how these complex sugar chains are synthesized and degraded, and how the lysosomal dysfunction central to MPS disrupts these pathways.

The presentation delves into early clinical signs—many of which are subtle and non-specific. Infants may appear healthy but gradually develop symptoms like macrocephaly, snoring, recurrent ear infections, hernias, joint stiffness, and coarse facial features. Prof. Gerit-Kircher underscores that signs such as lumbar kyphosis, thickened fingers, corneal clouding, and early carpal tunnel syndrome should prompt suspicion of MPS.

She introduces the concept of “dysostosis multiplex”—a set of skeletal abnormalities characteristic of MPS—highlighting changes in the skull, spine, ribs, and limbs as seen on radiographs. These features remain key diagnostic indicators and should alert radiologists and pediatricians to consider MPS in their differential diagnoses.

The session then contrasts the classical Hurler and Scheie phenotypes. Hurler syndrome presents in infancy with severe developmental delay, cognitive impairment, organomegaly, and rapid progression. Scheie patients, by contrast, may have normal intelligence, present later in life, and primarily exhibit joint, cardiac, and ocular issues. Importantly, Prof. Gerit-Kircher explains that most MPS I patients fall somewhere between these extremes.

She also discusses genotype-phenotype correlations, noting that while certain mutations can predict disease severity, individual presentations may vary. Treatment options, including hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT), are most effective when started early. New clinical trials—including intrathecal ERT and gene therapy—offer future hope.

The webinar concludes with practical diagnostic recommendations: start with urinary GAG analysis, confirm with enzyme assays, and use genetic panels when needed. Above all, early recognition—especially by general pediatricians—can dramatically improve outcomes for children with MPS I.

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