Mucopolysaccharidoses (MPS) - Established & Emerging Treatments

Dr. Wang begins by explaining how MPS results from deficiencies in lysosomal enzymes needed to break down glycosaminoglycans (GAGs). When this breakdown fails, GAGs accumulate across multiple organ systems—including the central nervous system (CNS), eyes, joints, heart, and liver—leading to progressive symptoms. MPS I is used as the primary example, with attention to its clinical spectrum: from severe Hurler syndrome to the attenuated Scheie phenotype.

He highlights early symptoms such as macrocephaly, coarse facial features, hernias, frequent infections, kyphosis, and joint stiffness. Before the era of newborn screening, these children often saw multiple specialists—ENTs, surgeons, orthopedists—before receiving a correct diagnosis. Radiological findings like “dysostosis multiplex,” with hook-shaped vertebrae and pointed metacarpals, can provide critical diagnostic clues.

Diagnosis involves a tiered approach: urinary GAG quantification (especially dermatan and heparan sulfate), enzyme activity testing (e.g., alpha-iduronidase), and genetic sequencing. He emphasizes that some cases require multiple testing modalities, including tandem mass spectrometry and molecular panels, to confirm MPS subtypes.

Dr. Wang then turns to treatment options. Enzyme replacement therapy (ERT) for MPS I has been available since 2003 and is effective at reducing soft tissue GAG storage, improving endurance and respiratory function. However, due to poor vascularization, ERT has limited impact on joints, heart valves, cornea, and CNS. Weekly infusions also require central lines and carry risks of infusion reactions.

Hematopoietic stem cell transplantation (HSCT), particularly in infants diagnosed early, remains the only effective strategy to prevent cognitive decline in severe MPS I. Engrafted donor cells migrate to the brain and produce enough enzyme to prevent neurologic regression. Dr. Wang notes that newborn screening now enables earlier HSCT and better outcomes.

He concludes by touching on other MPS types, including MPS II (Hunter syndrome) and MPS III (Sanfilippo), for which CNS-targeted treatments remain under investigation. His closing message: early suspicion, prompt diagnosis, and timely treatment initiation are key to transforming the lives of children with MPS.