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MPS I: an overview

Patients with mucopolysaccharidosis (MPS) I are at increased risk for severe morbidity and early mortality1

MPS I is a progressive condition2 that has been divided into 3 subtypes known as Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S).3 All subtypes of MPS I are caused by a deficiency of the enzyme α-L-iduronidase, which is required for the degradation of the glycosaminoglycans (GAGs) heparan sulphate and dermatan sulphate,2,4 with resulting progressive, multisystemic manifestations.2

  • MPS I-H typically presents within the first 2 years of life with developmental delay, cognitive decline and rapid progression1,2
  • MPS I-H/S typically presents between the ages of 3 and 7 with mild or absent cognitive decline and slower progression1,2
  • MPS I-S typically presents between the ages of 5 and 13 with no cognitive decline and slower progression1,2
Observed presentation
  • Symptoms appear at varying ages depending on the specific enzyme deficiency and rate of disease progression:1
    • H, ages 0 to 2
    • H/S, ages 3 to 7
    • S, ages 5 to 13
  • Observed presentation includes:5
    • Change in facial features
    • Restricted joint movement
    • Skeletal deformity
    • Macrocephaly
    • Frequent respiratory infections
    • Cardiomyopathy
    • Recurrent ear infections
    • Hernias
    • Kyphosis/gibbus deformity
  • Specific recommendations for consideration of MPS I include:6
    • Children with gibbus deformity, enlarged tongue, and/or 2 or more surgeries before 18 months should prompt diagnostic testing
    • Children over 2 years of age with claw hands, cardiac problems and/or 2 or more surgeries before age 10 should prompt diagnostic testing
Disease progression
  • Overall disease burden:
    • Patients experience multiorgan dysfunction and have a high disease burden1
    • This progressive, debilitating disease also puts psychological and financial burdens on patients and their families5
  • Hurler (H):
    • Symptoms appear shortly after birth, progress rapidly, and typically include:1
      • Developmental delay and cognitive decline
      • Coarse facial features
      • Joint stiffness and contractures
      • Short stature
      • Hepatosplenomegaly
      • Respiratory and cardiac disease
    • Left untreated, patients typically die within the first decade of life, often due to cardiorespiratory failure and neurological disease1,5
  • Hurler-Scheie (H/S) and Scheie (S):
    • Symptom presentation varies according to age7:
      • Hernia typically occurs before age 5
      • Joint contractures and dysostosis multiplex typically arise between the ages of 5 and 12
      • Scoliosis, carpal tunnel syndrome, and congestive heart failure often occur in adolescence
      • Glaucoma, cardiomyopathy, and myelopathy typically arise in early adulthood
    • Left untreated, patients with MPS I-H/S typically die within the second or third decade of life1
    • Left untreated, patients with MPS I-S usually sustain significant morbidity1
  • Patients with MPS I have a high surgical burden, which may include:6
    • Myringotomies
    • Hernia surgery, often with repeat procedures
    • Adenoidectomy
    • Tonsillectomy
    • Ventriculoperitoneal shunt
    • Spinal procedures
    • Carpal tunnel surgery
    • Orthopaedic surgeries of hip, knee and foot
  • Because patients with MPS I often experience anaesthetic complications due to obstructed airways, special care must be taken when undergoing surgery8
Genetic information
  • MPS I is caused by mutations in the α-L-iduronidase gene, IDUA4
  • There are over 100 known pathogenic variants within IDUA9
  • These mutations lead to accumulation of the GAGs heparan and dermatan sulphate4
Key management considerations
  • The potential use of enzyme replacement therapy and hematopoietic stem cell transplantation (HSCT) are both important considerations in the management of MPS I:1,5
  • Patients with the Hurler phenotype diagnosed before 2.5 years should be treated with HSCT10
  • All other patients should be treated with enzyme replacement therapy.10
  • Available treatment guidelines include:
    • Martins AM et al. Guidelines for the management of mucopolysaccharidosis type I. J Pediatr 2009;155(4)(suppl 2):S32–S46.
    • Muenzer J et al. International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 2009;123(1):19–29.
    • de Ru MH et al. Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis 2011;6(55):1–9.
    • Langereis EJ et al. Treatment of hip dysplasia in patients with mucopolysaccharidosis type I after hematopoietic stem cell transplantation: results of an international consensus procedure. Orphanet J Rare Dis 2013;8(155):1–16.

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References:  1. Beck M et al. The natural history of MPS I: global perspectives from the MPS I Registry. Genet Med.2014;16(10):759–765.   2. Clarke LA et al. Long-term efficacy and safety of laronidase in the treatment of mucopolysaccharidosis I. Pediatrics 2009;132(1):229–240.   3. Yasuda E et al. Long-term follow-up of post hematopoietic stem cell transplantation for Hurler syndrome: clinical, biochemical, and pathological improvements. Mol Genet Metab Rep 2015;2:65–76.   4. Shapiro EG et al. Neurocognition across the spectrum of mucopolysaccharidosis type I: age, severity, and treatment. Mol Genet Metab 2015;116(1-2):61–68.   5. Muenzer J et al. International Consensus Panel on the Management and Treatment of Mucopolysaccharidosis I. Mucopolysaccharidosis I: management and treatment guidelines. Pediatrics 2009;123(1):19–29.   6. Arn P et al. Characterization of surgical procedures in patients with mucopolysaccharidosis type I: findings from the MPS I Registry. J Pediatr 2009;154(6):859–864.e3.   7. Thomas JA et al. Childhood onset of Scheie syndrome, the attenuated form of mucopolysaccharidosis I. J Inherit Metab Dis 2010;33(4):421–427.   8. Semenza GL et al. Respiratory complications of mucopolysaccharide storage disorders. Medicine 1988;67(4):209–219.  9. Clarke LA et al. Mucopolysaccharidosis type I. In: Pagon RA et al eds. GeneReviews® Seattle, WA: University of Washington, Seattle; 2002. http://www.ncbi.nlm.nih.gov/books/NBK1162/?report=reader. Accessed July 31, 2015.  10. de Ru MH et al. Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis. 2011;6(55):1–9.