Clinical Features & Enzyme Replacement Therapy in MPS

Dr. Lagler begins by situating MPS within the broader context of lysosomal storage diseases (LSDs), explaining that MPS encompasses seven main subtypes and several variants. He emphasizes the multisystemic and often progressive nature of the disease, noting that approximately 70% of patients present with central nervous system (CNS) involvement. Using historical references and vivid clinical examples, he outlines hallmark signs such as short stature, macrocephaly, joint contractures, coarse facial features, ENT complications, and skeletal deformities (dysostosis multiplex).

He describes how diagnosis hinges on identifying a constellation of symptoms—often involving the skeletal system, CNS, and visceral organs—rather than a single red flag. However, early-onset carpal tunnel syndrome or claw-hand deformity in children are specific signs that should prompt suspicion of MPS. Imaging, urine glycosaminoglycan (GAG) testing, enzyme assays, and genetic analysis are the mainstays of diagnosis.

The webinar provides a detailed account of ERT, now available for several MPS types (I, II, IV, VI, and VII). Dr. Lagler explains how recombinant enzymes administered via weekly infusions can reduce GAG accumulation, improve endurance and lung function, and slow disease progression. However, he is candid about its limitations—ERT does not significantly affect skeletal deformities or CNS symptoms, due largely to poor enzyme penetration into bones and across the blood-brain barrier.

He discusses infusion-related reactions, stressing the importance of premedication with antihistamines, ibuprofen, or steroids, and careful handling of enzymes to prevent denaturation. Despite occasional side effects, ERT is well-tolerated and can be administered at home.

Dr. Lagler also reviews emerging therapeutic strategies: intrathecal ERT for CNS access, pharmacological chaperones, receptor-mediated delivery (Trojan horse approach), gene therapy (in vivo and ex vivo), and implantable bioreactors. These aim to enhance enzyme delivery, achieve continuous therapeutic levels, and overcome current barriers to efficacy.

The session concludes with an appeal for early diagnosis and referral, emphasizing the need for a multidisciplinary care team and the promise of new therapies on the horizon. Recognizing subtle patterns in symptoms and acting swiftly can dramatically alter the trajectory for children with MPS.

‍