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Mucopolysaccharidosis, MPS-I-S(MPS1-S; MPS5, FORMERLY)

MedGen UID:
6453
Concept ID:
C0026708
Disease or Syndrome
Synonyms: MPS V; MUCOPOLYSACCHARIDOSIS TYPE IS; MUCOPOLYSACCHARIDOSIS TYPE V; Scheie Syndrome
SNOMED CT: Mucopolysaccharidosis, MPS-I-S (73123008); Scheie's syndrome (73123008); L-iduronidase deficiency, Scheie type (73123008); Mucopolysaccharidosis type I mild form (73123008); Mucopolysaccharidosis type I-S (73123008); MPS 1-S - Mucopolysaccharidosis type I-S (73123008); Scheie disease MPS type 1S (73123008)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): IDUA (4p16.3)
 
Monarch Initiative: MONDO:0011760
OMIM®: 607016
Orphanet: ORPHA93474

Disease characteristics

Excerpted from the GeneReview: Mucopolysaccharidosis Type I
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. Affected individuals are best described as having either a phenotype consistent with either severe (Hurler syndrome) 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, as is progressive arthropathy involving most joints. By age three years, linear growth decreases. Intellectual disability is progressive and profound but may not be readily apparent in the first year of life. Progressive cardiorespiratory involvement, hearing loss, and corneal clouding are common. Without treatment, death (typically from cardiorespiratory failure) usually occurs within the first ten years of life. Attenuated MPS I: Clinical onset is usually between ages three and ten years. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decade, 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 and psychiatric manifestations can be present later in life. Hearing loss, cardiac valvular disease, respiratory involvement, and corneal clouding are common. [from GeneReviews]
Authors:
Lorne A Clarke   view full author information

Additional description

From OMIM
The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs), or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypic involvement with 3 major recognized clinical entities: Hurler (MPS IH; 607014), Hurler-Scheie (MPS IH/S; 607015), and Scheie (MPS IS) syndromes. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression (McKusick, 1972).  http://www.omim.org/entry/607016

Clinical features

From HPO
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Pes cavus
MedGen UID:
675590
Concept ID:
C0728829
Congenital Abnormality
An increase in height of the medial longitudinal arch of the foot that does not flatten on weight bearing (i.e., a distinctly hollow form of the sole of the foot when it is bearing weight).
Aortic regurgitation
MedGen UID:
8153
Concept ID:
C0003504
Disease or Syndrome
An insufficiency of the aortic valve, leading to regurgitation (backward flow) of blood from the aorta into the left ventricle.
Aortic valve stenosis
MedGen UID:
1621
Concept ID:
C0003507
Pathologic Function
The presence of a stenosis (narrowing) of the aortic valve.
Mitral stenosis
MedGen UID:
44466
Concept ID:
C0026269
Disease or Syndrome
An abnormal narrowing of the orifice of the mitral valve.
Obstructive sleep apnea syndrome
MedGen UID:
101045
Concept ID:
C0520679
Disease or Syndrome
Obstructive sleep apnea is a common, chronic, complex disease associated with serious cardiovascular and neuropsychologic sequelae and with substantial social and economic costs (Palmer et al., 2003).
Cervical cord compression
MedGen UID:
167271
Concept ID:
C0852866
Finding
Compression of the spinal cord in the cervical region, generally manifested by paresthesias and numbness, weakness, difficulty walking, abnormalities of coordination, and neck pain or stiffness.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Constrictive median neuropathy
MedGen UID:
868610
Concept ID:
C4023009
Anatomical Abnormality
Injury to the median nerve caused by its entrapment at the wrist as it traverses through the carpal tunnel. Clinically, constrictive median neuropathy is characterized by pain, paresthesia, and weakness in the median nerve distribution of the hand.
Spondylolisthesis
MedGen UID:
52470
Concept ID:
C0038016
Disease or Syndrome
Spondylolisthesis is defined as forward slipping of a vertebral body on the one below it. Spondylolysis is defined as a defect in the pars interarticularis without vertebral slipping (summary by Wiltse et al., 1975).
Hurler syndrome
MedGen UID:
39698
Concept ID:
C0086795
Disease or Syndrome
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. Affected individuals are best described as having either a phenotype consistent with either severe (Hurler syndrome) 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, as is progressive arthropathy involving most joints. By age three years, linear growth decreases. Intellectual disability is progressive and profound but may not be readily apparent in the first year of life. Progressive cardiorespiratory involvement, hearing loss, and corneal clouding are common. Without treatment, death (typically from cardiorespiratory failure) usually occurs within the first ten years of life. Attenuated MPS I. Clinical onset is usually between ages three and ten years. The severity and rate of disease progression range from serious life-threatening complications leading to death in the second to third decade, 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 and psychiatric manifestations can be present later in life. Hearing loss, cardiac valvular disease, respiratory involvement, and corneal clouding are common.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Wide nose
MedGen UID:
140869
Concept ID:
C0426421
Finding
Interalar distance more than two standard deviations above the mean for age, i.e., an apparently increased width of the nasal base and alae.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Broad face
MedGen UID:
349223
Concept ID:
C1859680
Finding
Bizygomatic (upper face) and bigonial (lower face) width greater than 2 standard deviations above the mean (objective); or an apparent increase in the width of the face (subjective).
Full cheeks
MedGen UID:
355661
Concept ID:
C1866231
Finding
Increased prominence or roundness of soft tissues between zygomata and mandible.
Corneal opacity
MedGen UID:
40485
Concept ID:
C0010038
Finding
A reduction of corneal clarity.
Glaucoma
MedGen UID:
42224
Concept ID:
C0017601
Disease or Syndrome
Glaucoma refers loss of retinal ganglion cells in a characteristic pattern of optic neuropathy usually associated with increased intraocular pressure.
Retinal degeneration
MedGen UID:
48432
Concept ID:
C0035304
Finding
A nonspecific term denoting degeneration of the retinal pigment epithelium and/or retinal photoreceptor cells.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Mucopolysaccharidosis, MPS-I-S in Orphanet.

Professional guidelines

PubMed

Burlina AB, Gragnaniello V
Crit Rev Clin Lab Sci 2022 Jun;59(4):257-277. Epub 2022 Jan 17 doi: 10.1080/10408363.2021.2021846. PMID: 35037566
Spahiu L, Behluli E, Peterlin B, Nefic H, Hadziselimovic R, Liehr T, Temaj G
Pediatr Endocrinol Diabetes Metab 2021;27(3):201-208. doi: 10.5114/pedm.2021.109270. PMID: 34743503Free PMC Article
Donati MA, Pasquini E, Spada M, Polo G, Burlina A
Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. doi: 10.1186/s13052-018-0552-3. PMID: 30442156Free PMC Article

Curated

ACMG Algorithm, MPS I: Decreased Alpha-L-Iduronidase; Elevated Dermatan and Heparan Sulfates, 2023

American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, alpha-L-iduronidase deficiency with or without glycosaminoglycan (GAG) accumulation, Mucopolysaccharidosis Type 1 (MPS I), 2023

Recent clinical studies

Etiology

Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group
N Engl J Med 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596. PMID: 34788506
Hurt SC, Dickson PI, Curiel DT
J Inherit Metab Dis 2021 Sep;44(5):1088-1098. Epub 2021 Jul 9 doi: 10.1002/jimd.12414. PMID: 34189746Free PMC Article
Donati MA, Pasquini E, Spada M, Polo G, Burlina A
Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. doi: 10.1186/s13052-018-0552-3. PMID: 30442156Free PMC Article
Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S
Mol Genet Metab 2017 Jul;121(3):227-240. Epub 2017 May 26 doi: 10.1016/j.ymgme.2017.05.016. PMID: 28595941Free PMC Article
Wraith JE, Jones S
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:102-6. PMID: 25345091

Diagnosis

Burlina AB, Gragnaniello V
Crit Rev Clin Lab Sci 2022 Jun;59(4):257-277. Epub 2022 Jan 17 doi: 10.1080/10408363.2021.2021846. PMID: 35037566
Spahiu L, Behluli E, Peterlin B, Nefic H, Hadziselimovic R, Liehr T, Temaj G
Pediatr Endocrinol Diabetes Metab 2021;27(3):201-208. doi: 10.5114/pedm.2021.109270. PMID: 34743503Free PMC Article
Kingma SDK, Jonckheere AI
J Inherit Metab Dis 2021 Nov;44(6):1289-1310. Epub 2021 Sep 15 doi: 10.1002/jimd.12431. PMID: 34480380
Donati MA, Pasquini E, Spada M, Polo G, Burlina A
Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. doi: 10.1186/s13052-018-0552-3. PMID: 30442156Free PMC Article
Wraith JE, Jones S
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:102-6. PMID: 25345091

Therapy

Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group
N Engl J Med 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596. PMID: 34788506
Parini R, Deodato F, Di Rocco M, Lanino E, Locatelli F, Messina C, Rovelli A, Scarpa M
Orphanet J Rare Dis 2017 Jun 15;12(1):112. doi: 10.1186/s13023-017-0662-9. PMID: 28619065Free PMC Article
Wraith JE, Jones S
Pediatr Endocrinol Rev 2014 Sep;12 Suppl 1:102-6. PMID: 25345091
BioDrugs 2002;16(4):316-8. doi: 10.2165/00063030-200216040-00009. PMID: 12196045
Wraith JE
J Inherit Metab Dis 2001 Apr;24(2):245-50. doi: 10.1023/a:1010379320378. PMID: 11405343

Prognosis

Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group
N Engl J Med 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596. PMID: 34788506
Donati MA, Pasquini E, Spada M, Polo G, Burlina A
Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. doi: 10.1186/s13052-018-0552-3. PMID: 30442156Free PMC Article
Khan SA, Peracha H, Ballhausen D, Wiesbauer A, Rohrbach M, Gautschi M, Mason RW, Giugliani R, Suzuki Y, Orii KE, Orii T, Tomatsu S
Mol Genet Metab 2017 Jul;121(3):227-240. Epub 2017 May 26 doi: 10.1016/j.ymgme.2017.05.016. PMID: 28595941Free PMC Article
Shapiro EG, Nestrasil I, Rudser K, Delaney K, Kovac V, Ahmed A, Yund B, Orchard PJ, Eisengart J, Niklason GR, Raiman J, Mamak E, Cowan MJ, Bailey-Olson M, Harmatz P, Shankar SP, Cagle S, Ali N, Steiner RD, Wozniak J, Lim KO, Whitley CB
Mol Genet Metab 2015 Sep-Oct;116(1-2):61-8. Epub 2015 Jun 17 doi: 10.1016/j.ymgme.2015.06.002. PMID: 26095521Free PMC Article
Wraith EJ, Hopwood JJ, Fuller M, Meikle PJ, Brooks DA
BioDrugs 2005;19(1):1-7. doi: 10.2165/00063030-200519010-00001. PMID: 15691212

Clinical prediction guides

Miller BS, Fung EB, White KK, Lund TC, Harmatz P, Orchard PJ, Whitley CB, Polgreen LE
J Inherit Metab Dis 2023 Jul;46(4):695-704. Epub 2023 Mar 6 doi: 10.1002/jimd.12598. PMID: 36840680Free PMC Article
Kovac V, Shapiro EG, Rudser KD, Mueller BA, Eisengart JB, Delaney KA, Ahmed A, King KE, Yund BD, Cowan MJ, Raiman J, Mamak EG, Harmatz PR, Shankar SP, Ali N, Cagle SR, Wozniak JR, Lim KO, Orchard PJ, Whitley CB, Nestrasil I
Mol Genet Metab 2022 Feb;135(2):122-132. Epub 2022 Jan 7 doi: 10.1016/j.ymgme.2022.01.001. PMID: 35012890Free PMC Article
Gentner B, Tucci F, Galimberti S, Fumagalli F, De Pellegrin M, Silvani P, Camesasca C, Pontesilli S, Darin S, Ciotti F, Sarzana M, Consiglieri G, Filisetti C, Forni G, Passerini L, Tomasoni D, Cesana D, Calabria A, Spinozzi G, Cicalese MP, Calbi V, Migliavacca M, Barzaghi F, Ferrua F, Gallo V, Miglietta S, Zonari E, Cheruku PS, Forni C, Facchini M, Corti A, Gabaldo M, Zancan S, Gasperini S, Rovelli A, Boelens JJ, Jones SA, Wynn R, Baldoli C, Montini E, Gregori S, Ciceri F, Valsecchi MG, la Marca G, Parini R, Naldini L, Aiuti A, Bernardo ME; MPSI Study Group
N Engl J Med 2021 Nov 18;385(21):1929-1940. doi: 10.1056/NEJMoa2106596. PMID: 34788506
Donati MA, Pasquini E, Spada M, Polo G, Burlina A
Ital J Pediatr 2018 Nov 16;44(Suppl 2):126. doi: 10.1186/s13052-018-0552-3. PMID: 30442156Free PMC Article
Poletto E, Pasqualim G, Giugliani R, Matte U, Baldo G
Clin Genet 2018 Jul;94(1):95-102. Epub 2018 Apr 11 doi: 10.1111/cge.13224. PMID: 29393969

Recent systematic reviews

Dornelles AD, Artigalás O, da Silva AA, Ardila DLV, Alegra T, Pereira TV, Vairo FPE, Schwartz IVD
PLoS One 2017;12(8):e0184065. Epub 2017 Aug 31 doi: 10.1371/journal.pone.0184065. PMID: 28859139Free PMC Article
Pérez-López J, Morales-Conejo M, López-Rodríguez M, Hermida-Ameijeiras Á, Moltó-Abad M
Mol Genet Metab 2017 Jun;121(2):138-149. Epub 2017 Apr 9 doi: 10.1016/j.ymgme.2017.04.004. PMID: 28410878
Jameson E, Jones S, Remmington T
Cochrane Database Syst Rev 2016 Apr 1;4:CD009354. doi: 10.1002/14651858.CD009354.pub4. PMID: 27033167
Jameson E, Jones S, Wraith JE
Cochrane Database Syst Rev 2013 Nov 21;(11):CD009354. doi: 10.1002/14651858.CD009354.pub3. PMID: 24257962
Jameson E, Jones S, Wraith JE
Cochrane Database Syst Rev 2013 Sep 26;(9):CD009354. doi: 10.1002/14651858.CD009354.pub2. PMID: 24085657

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG Algorithm, 2023
      ACMG Algorithm, MPS I: Decreased Alpha-L-Iduronidase; Elevated Dermatan and Heparan Sulfates, 2023
    • ACMG ACT, 2023
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, alpha-L-iduronidase deficiency with or without glycosaminoglycan (GAG) accumulation, Mucopolysaccharidosis Type 1 (MPS I), 2023

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