Table 6.

Mucopolysaccharidosis Type I: Targeted Treatment

Targeted TreatmentIndication/DosageBenefitsConsideration
Hematopoietic stem cell transplantation (HSCT) 1, 2 Considered the standard of care for children w/MPS I & is generally recommended to be performed before age 2 years to maximize benefit
  • Improved survival 3
  • Reduction in facial coarseness & hepatosplenomegaly, & improvement in hearing 4
  • Initial stabilization & improvement in myocardial function w/regression of hypertrophy & normalization of chamber dimensions; however, long-term follow up shows continued progression of valvular involvement 3
  • • HSCT is the only therapeutic approach that alters the natural history of neurocognitive disease in MPS I. 5, 6
  • HSCT has more limited impact on cardiac valvular, ocular, & skeletal manifestations. 7, 8
  • Outcome from HSCT is significantly influenced by disease burden at time of diagnosis (& thus age of affected person). 9
  • HSCT has been successful in ↓ rate of progression of some findings in children w/severe MPS I.
Laronidase (Aldurazyme®) 10 enzyme replacement therapy (ERT)
  • Premedication w/anti-inflammatory & antihistamine drugs
  • Intravenous weekly infusion of 100 U/kg of Aldurazyme® over 4 hours
  • Package insert provides details that may differ by country.
Benefits have included: 11
  • ↓ & sustained urinary GAG levels 12
  • Normalization of hepatic & splenic volume
  • Stabilization (but not improvement) in respiratory function
  • Gradual ↑ in shoulder range of motion (typically w/in 1st 2 years, then plateauing)
  • Improvements in mobility w/in 1st 2 years 13
  • Improvement in quality of life index
  • Currently licensed widely for use in treating non-CNS manifestations
  • Aldurazyme® does not cross blood-brain barrier & thus is not expected to influence CNS disease.
  • The effect on rate of disease progression & effect when started very early in a person w/attenuated disease has not been comprehensively studied.
  • ERT does not impact corneal involvement, cardiac valvular disease progression, progressive arthropathy of involved large joints & hands, & progressive spinal diseases w/cord compression.
  • Carpal tunnel syndrome remains a potential complication.

GAG = glycosaminoglycan

1.

HSCT is not curative but does significantly alter the natural history of the disorder.

2.

HSCT should be used only in carefully selected children with extensive pre-transplantation clinical assessment and counseling in whom systematic long-term monitoring will be possible [Aldenhoven et al 2015a, Aldenhoven et al 2015b]. Adults have not undergone HSCT.

3.
4.
5.
6.

The degree to which HSCT relieves neurologic complications other than progressive intellectual decline is not clear. In children undergoing HSCT before evidence of significant developmental delay (i.e., usually age 12-18 months), HSCT appears to slow the course of cognitive decline. Children showing significant cognitive impairment prior to undergoing HSCT do not show correction of existing impairment.

7.

In part because of increased longevity after HSCT, treated individuals develop increasing pain and stiffness of the hips and knees, carpal tunnel syndrome, spinal cord compression, and progressive thoracolumbar kyphosis. The age of HSCT appears to influence the age of onset of carpal tunnel syndrome and cervical compression.

8.

The skeletal manifestations and corneal clouding continue to progress in children treated with HSCT and in untreated children [van den Broek et al 2020b].

9.

Individuals who have received HSCT require continued multidisciplinary follow up and monitoring related to MPS I complications.

10.

Comparative sib studies indicate improved outcomes when ERT is initiated early in the disease course.

11.
12.

Response is usually within 12 weeks, with some individuals achieving normal values.

13.

As measured by timed-walk measurements; after two years mobility may be variably affected by hip, knee, and spinal disease progression.

From: Mucopolysaccharidosis Type I

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