Send to

Choose Destination

Mucopolysaccharidosis Type I.


Clarke LA1.


GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2019.
2002 Oct 31 [updated 2016 Feb 11].

Author information

Professor, Medical Genetics, University of British Columbia, Vancouver, BC, Canada



Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. While affected individuals have traditionally been classified as having one of three MPS I syndromes (Hurler syndrome, Hurler-Scheie syndrome, or Scheie syndrome), no easily measurable biochemical differences have been identified and the clinical findings overlap; thus, affected individuals are best described as having either severe or attenuated MPS I, a distinction that influences therapeutic options. Severe MPS I. Infants appear normal at birth. Typical early manifestations are nonspecific (e.g., umbilical or inguinal hernia, frequent upper respiratory-tract infections before age 1 year). Coarsening of the facial features may not become apparent until after age one year. Gibbus deformity of the lower spine is common and often noted within the first year. Progressive skeletal dysplasia (dysostosis multiplex) involving all bones is universal. By age three years, linear growth decreases. Intellectual disability is progressive and profound. Hearing loss is common. Death, typically caused by cardiorespiratory failure, usually occurs within the first ten years of life. Attenuated MPS I. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decades to a normal life span complicated by significant disability from progressive joint manifestations and cardiorespiratory disease. While some individuals have no neurologic involvement and psychomotor development may be normal in early childhood, learning disabilities can be present. Clinical onset is usually between ages three and ten years. Hearing loss and cardiac valvular disease are common.


The diagnosis of MPS I is established in a proband with suggestive clinical and laboratory findings and either identification of biallelic pathogenic variants in IDUA on molecular genetic testing or detection of deficient activity of the lysosomal enzyme α-L-iduronidase.


Treatment of manifestations: Infant learning programs/special education for developmental delays; hats with visors/sunglasses to reduce glare; cardiac valve replacement as needed; physical therapy, orthopedic surgery as needed (joint replacement, atlanto-occipital stabilization, early median nerve decompression for carpal tunnel syndrome based on nerve conduction studies before clinical manifestations develop); cerebrospinal fluid (CSF) shunting for hydrocephalus; tonsillectomy and adenoidectomy for eustachian tube dysfunction and/or upper airway obstruction; tracheostomy for sleep apnea, pulmonary hypertension, right heart failure; PE tubes; surgical intervention for cervical myelopathy. Prevention of primary manifestations: Hematopoietic stem cell transplantation (HSCT) is considered as standard of care for children with severe MPS I. Outcome from HSCT is significantly influenced by disease burden at the time of diagnosis (and thus, by the age of the patient). HSCT can increase survival, improve growth, reduce facial coarseness and hepatosplenomegaly, improve hearing, and alter the natural history of cardiac and respiratory symptomatology. HSCT has lesser effects on the skeletal and joint manifestations or corneal clouding. HSCT may slow the course of cognitive decline in children with mild, but not significant, cognitive impairment at the time of transplantation. Due to the morbidity and mortality associated with HSCT, it is currently recommended primarily for children with severe MPS I. Enzyme replacement therapy (ERT) with laronidase (Aldurazyme®), licensed for treatment of the non-CNS manifestations of MPS I, improves liver size, linear growth, joint mobility, breathing, and sleep apnea in persons with attenuated disease. The timing of the initiation of ERT is likely to influence the outcome. Prevention of secondary complications: Bacterial endocarditis prophylaxis for those with cardiac involvement; special attention to anesthetic risks. Surveillance: Early and continuous monitoring of head growth in infants and children; routine median nerve conduction velocity testing; and educational assessment of children with attenuated disease prior to primary school entry. Annual assessment by: orthopedic surgeon, neurologist (for evidence of spinal cord compression), ophthalmologist, cardiologist (including echocardiogram), audiologist, and otolaryngologist. Evaluation of relatives at risk: Early diagnosis prior to significant disease manifestations is warranted in relatives at risk in order to begin therapy as early in the course of disease as possible.


MPS I is inherited in an autosomal recessive manner. At conception, each child of a couple in which both parents are heterozygous for a IDUA pathogenic variant has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk relatives and prenatal testing for pregnancies at increased risk are possible if both pathogenic IDUA variants have been identified in the family.

Copyright © 1993-2019, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

Supplemental Content

Support Center