Mucopolysaccharidosis type I (MPS I) clinical features and symptom presentation

Patients with mucopolysaccharidosis (MPS) I face a multitude of serious and often debilitating multisystemic manifestations.

In MPS I, the alpha-L-iduronidase (IDUA) enzyme is deficient or essentially absent, causing glycosaminoglycans (GAGs) substrates to accumulate in cells, leading to progressive damage to tissues and organs.^1-7 Learn more about the pathophysiology of MPS I.

Understanding the range of mucopolysaccharidosis type I symptoms

MPS I can present with a wide spectrum of signs and symptoms.  It is therefore important to identify the common manifestations across the spectrum of MPS I to piece together the diagnosis of this potentially fatal disease.⁶

MPS I characteristics

The types of MPS I include the severe form (Hurler syndrome) and the attenuated form (Hurler-Scheie and Scheie syndrome). These phenotypes differ in disease severity and speed of progression, however, show overlapping clinical features.^6,8

Hurler and Hurler-Scheie syndrome symptoms are both characterized by cognitive deficits⁸ while Scheie syndrome has no cognitive impairment.⁷

MPS I Can Present with a Wide Array of Signs and Symptoms

Features and symptoms of severe and attenuated MPS I forms

^aScheie form has no cognitive impairment.

The MPS I disease spectrum is marked by heterogeneity that can complicate diagnosis, with varying ages of onset, unusual symptom combinations, and a broad range of sometimes life-limiting and life-threatening clinical manifestations.^6,8

Mucopolysaccharidosis type I facial features

The appearance of some infants with severe and moderate-to-severe symptoms of MPS I may appear unaffected at birth, but as early as 3 months of age, parents may notice changes in their child’s facial features.⁹

Pronounced facial features of MPS I include:

• Enlarged lips and cheeks⁵
• Short noses, flat faces, prominent foreheads⁴
• Large heads, which tend to be longer than normal from front to back (scaphocephaly)⁴

Some individuals with the severe form of MPS I have macroglossia, characterized by an abnormally large tongue which protrudes past the dental arch when the mouth is closed, making swallowing and speaking difficult.^10,11

Mucopolysaccharidosis type I ocular manifestations

Corneal clouding of the eye is usually one of the first ocular manifestations in patients with the severe form of MPS I.^11–13

The accumulation of GAGs and subsequent disorganization of collagen fibrils in the cornea cause corneal opacity.^11,13 Corneal clouding often starts within the first year of life, causing vision impairment and often leading to blindness.^12,14 Retinal degeneration and optic nerve compression can also manifest in children.^12,13

Mucopolysaccharidosis type I musculoskeletal manifestations

Adults are often stocky in build, their trunks shorter than their limbs, and their necks may be short and stiff.^4,9 Bone abnormalities are common in those with MPS I, including:

• Hip deformations¹⁵
• Ovoid vertebrae¹⁵
• Widening of the ribs.¹⁵
• Poorly formed pelvis^7,15
• Gibbus deformity of the back^7,15
• Shortened phalanges of the hands^7,15
• Joint contractures^7,16

Skeletal dysplasia can occur in the severe types of MPS I but is frequently missing or subclinical in patients with attenuated MPS I.¹⁵

Joint stiffness, pain and contractures are common among patients with attenuated MPS I.⁷ Evolving joint pain and joint contractures in the absence of inflammation should always raise suspicion of an MPS disorder.¹⁶

Limited range of motion mobility in the absence of inflammation should raise suspicion of MPS I.

Cardiovascular manifestations

Cardiovascular manifestations are common in patients with MPS I.¹⁸ In particular, cardiomyopathy and endocardial fibroelastosis can occur in children with severe MPS I.¹¹ Patients with an attenuated form of MPS I may develop aortic or mitral valve disease, and this can lead to a slowly progressive valvular heart disease over several years.¹⁸ In some cases, these patients may need mitral or aortic valve replacement as early as in their teens and twenties.¹⁸

Developmental manifestations

Developmental delays are apparent in the severe form of MPS I starting at 12–24 months of age, typically with a maximum functional age of 2–4 years.¹⁹ The initial presentation of delay is then followed by slowed development and progressive regression in developmental skills until death.²⁰

Mildly affected patients with the attenuated form generally have unaffected cognition.⁷

Diagnosing and managing mucopolysaccharidosis type I patients

Recognizing symptoms and making an accurate early diagnosis are critical for MPS I disease management.³ Some common symptoms of MPS I can be similar to the symptoms of other diseases.

As MPS I can affect multiple organ systems, diagnosis and treatment may require collaboration and communication among geneticists, neurologists, pediatricians, developmental specialists, surgeons, cardiologists, gastroenterologists, physical therapists, and primary care providers.³

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References: 1. de Ru MH et al. Orphanet J Rare Dis. 2011;6(55):1-9. 2. Wraith JE. Expert Opin Pharmacother. 2005;6(3):489-506. 3. D’Aco K et al. Eur J Pediatr. 2012;171(6):911-919. 4. Scheie HG et al. Barness LA. Am J Ophthalmol. 1962;53:753-769. 5. Hampe CS et al. Cells. 2020;9(8):1838. 6. Beck M et al. Genet Med. 2014;16(10):759-765. 7. Neufeld EF et al. The Online Metabolic and Molecular Bases of Inherited Disease. Accessed May 1, 2025. https://ommbid.mhmedical.com/content.aspx?bookid=2709&sectionid=225544161 8. Kubaski F et al. Diagnostics (Basel). 2020;10(3):161. 9. Cleary MA, Wraith JE. Acta Paediatr. 1995;84(3):337-339. 10. Kutti Sridharan G, Rokkam VR. In: StatPearls. StatPearls Publishing;2025. Accessed May 1, 2025. https://www.ncbi.nlm.nih.gov/books/NBK560545/ 11. Sakuru R, Bollu PC. In: StatPearls. StatPearls Publishing;2025. Accessed May 1, 2025. https://www.ncbi.nlm.nih.gov/books/NBK2261/ 12. Ashworth JL et al. EYE. 2006;20(5):553-563. 13. Tomatsu S et al. J Clin Med. 2019;8(9):1467. 14. Vance M et al. Sci Rep. 2016;6(1):22131. 15. Clarke LA. GeneReviews^® [Internet]. Accessed May 1, 2025. https://www.ncbi.nlm.nih.gov/books/NBK1162/ 16. Cimaz R et al. Pediatr Rheumatol Online J. 2009;7(1):18. 17. Guffon N et al. Eur J Pediatr. 2019;178(4):593-603. 18. Braunlin EA et al. J Inherit Metab Dis. 2011;34(6):1183-1197. 19. Shapiro EG et al. Mol Genet Metab. 2017;122S:1-7. 20. Shapiro EG et al. Mol Genet Metab. 2015;116(1-2):61-68. 21. Tylki-Szymanska A et al. Acta Paediatr. 2018;107(8):1402-1408. 22. Thatayatikom A et al. StatPearls [Internet]. StatPearls Publishing; 2022. Accessed August 17, 2025. https://www.ncbi.nlm.mih.gov/books/BNK554605/ 23. Bhavani GSL et al. In: Adam MP, Arranger HH, Pagon RA, eds. GeneReviews^® [Internet]/ University of Washington, Seattle; 1993-2022. Accessed August 17, 2025. 24. Gupta V et al. Indian J Endocrinol Metab. 2011;15(Suppl 2):S99-S106. 25. Krakow D. Clin Perinatol. 2015;41(2):301-319, viii. 26. Lorne C et al. J Inborn Errors Metab Screen. 2018;7:1-12.