Two studies of Boudewijn van Binsbergen and colleagues published in the European and American Journal of Hand Surgery highlight how close collaboration between metabolic specialists and hand surgeons allows to pinpoint persistent hand problems in children with mucopolysaccharidosis type I (MPS I), even in the era of ‘effective’ systemic treatment.
MPS I is a rare lysosomal storage disorder in which accumulation of glycosaminoglycans (GAGs) leads to progressive, multisystem disease. Hematopoietic stem cell transplantation (HSCT) has significantly improved survival and systemic outcomes. However, these new studies from UMC Utrecht show that musculoskeletal complications—particularly in the hands—remain a major clinical challenge.
In a cohort of 33 patients followed at the national expertise centre, 39% developed trigger digits, typically around the age of five. The cumulative risk increased to 57% by age twelve. Triggering involved multiple fingers, particularly the index, middle and ring fingers, which added to overall impaired hand function. Surgical intervention proved highly effective. Release of the tendon pulley—most commonly the A1 pulley—resulted in resolution of pain and triggering and led to clear functional improvement in nearly all patients. Recurrence was rare and no major complications were reported during long-term follow-up.
In the same cohort, 82% developed carpal tunnel syndrome, typically around the age of three and a half. The cumulative risk increased to 95% by age fifteen. A release of the transverse carpal ligament was performed in most patients showing varying improvement in sensory and motor latency values. However, despite release of the transverse carpal ligament, recurrence was frequently diagnosed, increasing to a cumulative risk of 45% by age eleven. The mechanism underlying this high rate of recurrence has yet to be uncovered, but hypotheses will be researched by Boudewijn van Binsbergen and colleagues (UMC Utrecht).
Importantly, these complications occurred despite successful HSCT. Indeed, histopathological analysis demonstrated persistent accumulation of storage material in tendon pulley and carpal ligament tissues years after transplantation. The observed lack of clearance helps explain why connective tissues such as tendons remain difficult to treat with systemic therapy alone.
These studies underscore the importance of structured, multidisciplinary follow-up to monitor residual disease in this multifaceted disorder. At UMC Utrecht, patients are routinely assessed by a team of specialists, headed by pediatric metabolic physician Peter van Hasselt. Hand function is evaluated, and if necessary treated, by specialized hand surgeons, including Aebele Mink van der Molen.
According to the authors, this collaboration between metabolic medicine and surgery is critical. While systemic therapies address the underlying metabolic defect, they do not fully prevent local tissue pathology. Timely recognition of functional impairment and referral for surgery can therefore make a substantial difference in quality of life.
The findings also have implications for future research. Persistent GAG accumulation in connective tissue suggests that improved treatment strategies—such as increased enzyme availability through gene-augmented haematopoietic stem cell transplantation currently evaluated in the HURCULES study or therapies with better tissue penetration—may allow to prevent long-term complications.
Overall, the study reinforces that MPS I require lifelong, multidisciplinary care. Integrating metabolic expertise with surgical interventions enables clinicians to address both systemic disease and its local manifestations, ultimately improving outcomes for patients.
