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Mucopolysaccharidosis type 1

MedGen UID:
44171
Concept ID:
C0023786
Disease or Syndrome
Synonyms: Alpha-L-Iduronidase deficiency; Attenuated MPS I (subtype); Hurler syndrome (former subtype); Hurler-Scheie syndrome (former subtype); IDUA deficiency; MPS 1; MPS I; Mucopolysaccharidosis type I; Scheie syndrome (former subtype; formerly known as Mucopoly-saccharidosis type V); Severe MPS I (subtype)
SNOMED CT: Mucopolysaccharidosis, MPS-I (75610003); MPS I (75610003); L-iduronidase deficiency (75610003); MPSI - Mucopolysaccharidosis type I (75610003); Mucopolysaccharidosis type I (75610003); Alpha-L-iduronidase deficiency (75610003)
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).
 
Related gene: IDUA
 
Monarch Initiative: MONDO:0001586
Orphanet: ORPHA579

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 MedlinePlus Genetics
Mucopolysaccharidosis type I (MPS I) is a condition that affects many parts of the body. This disorder was once divided into three separate syndromes: Hurler syndrome (MPS I-H), Hurler-Scheie syndrome (MPS I-H/S), and Scheie syndrome (MPS I-S), listed from most to least severe. Because there is so much overlap between each of these three syndromes, MPS I is currently divided into the severe and attenuated types.

Children with MPS I often have no signs or symptoms of the condition at birth, although some have a soft out-pouching around the belly-button (umbilical hernia) or lower abdomen (inguinal hernia). People with severe MPS I generally begin to show other signs and symptoms of the disorder within the first year of life, while those with the attenuated form have milder features that develop later in childhood.

Individuals with MPS I may have a large head (macrocephaly), a buildup of fluid in the brain (hydrocephalus), heart valve abnormalities, distinctive-looking facial features that are described as "coarse," an enlarged liver and spleen (hepatosplenomegaly), and a large tongue (macroglossia). Vocal cords can also enlarge, resulting in a deep, hoarse voice. The airway may become narrow in some people with MPS I, causing frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea).

People with MPS I often develop clouding of the clear covering of the eye (cornea), which can cause significant vision loss. Affected individuals may also have hearing loss and recurrent ear infections.

Some individuals with MPS I have short stature and joint deformities (contractures) that affect mobility. Most people with the severe form of the disorder also have dysostosis multiplex, which refers to multiple skeletal abnormalities seen on x-ray. Carpal tunnel syndrome develops in many children with this disorder and is characterized by numbness, tingling, and weakness in the hand and fingers. Narrowing of the spinal canal (spinal stenosis) in the neck can compress and damage the spinal cord.

While both forms of MPS I can affect many different organs and tissues, people with severe MPS I experience a decline in intellectual function and a more rapid disease progression. Developmental delay is usually present by age 1, and severely affected individuals eventually lose basic functional skills (developmentally regress). Children with this form of the disorder usually have a shortened lifespan, sometimes living only into late childhood. Individuals with attenuated MPS I typically live into adulthood and may or may not have a shortened lifespan. Some people with the attenuated type have learning disabilities, while others have no intellectual impairments. Heart disease and airway obstruction are major causes of death in people with both types of MPS I.  https://medlineplus.gov/genetics/condition/mucopolysaccharidosis-type-i

Professional guidelines

PubMed

Herbst ZM, Hong X, Urdaneta L, Klein T, Waggoner C, Liao HC, Kubaski F, Giugliani R, Fuller M, Gelb MH
Mol Genet Metab 2023 Sep-Oct;140(1-2):107632. Epub 2023 Jun 24 doi: 10.1016/j.ymgme.2023.107632. PMID: 37407323Free PMC Article
Hollak CE, Weinreb NJ
Best Pract Res Clin Endocrinol Metab 2015 Mar;29(2):205-18. Epub 2014 Aug 27 doi: 10.1016/j.beem.2014.08.006. PMID: 25987174
Paciotti S, Persichetti E, Pagliardini S, Deganuto M, Rosano C, Balducci C, Codini M, Filocamo M, Menghini AR, Pagliardini V, Pasqui S, Bembi B, Dardis A, Beccari T
Clin Chim Acta 2012 Nov 20;413(23-24):1827-31. Epub 2012 Jul 20 doi: 10.1016/j.cca.2012.07.011. PMID: 22820396

Curated

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

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

Recent clinical studies

Etiology

Yılmaz Çebi A, Hepokur M
Ophthalmic Genet 2023 Jun;44(3):273-275. Epub 2022 Jul 25 doi: 10.1080/13816810.2022.2103836. PMID: 35876331
Hampe CS, Polgreen LE, Lund TC, McIvor RS
Pediatr Endocrinol Rev 2020 Aug;17(4):317-326. doi: 10.17458/per.vol17.2020.hpl.dysostosismultiplexhumananimal. PMID: 32780955
Zahoor MY, Cheema HA, Ijaz S, Anjum MN, Ramzan K, Bhinder MA
J Pediatr Endocrinol Metab 2019 Nov 26;32(11):1221-1227. doi: 10.1515/jpem-2019-0188. PMID: 31473686
Brown N, Song L, Kollu NR, Hirsch ML
Hum Gene Ther 2017 Jun;28(6):450-463. doi: 10.1089/hum.2017.038. PMID: 28490211Free PMC Article
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA
Arch Dis Child 2009 Jan;94(1):52-4. Epub 2008 May 7 doi: 10.1136/adc.2007.135772. PMID: 18463126

Diagnosis

Hampe CS, Polgreen LE, Lund TC, McIvor RS
Pediatr Endocrinol Rev 2020 Aug;17(4):317-326. doi: 10.17458/per.vol17.2020.hpl.dysostosismultiplexhumananimal. PMID: 32780955
Zahoor MY, Cheema HA, Ijaz S, Anjum MN, Ramzan K, Bhinder MA
J Pediatr Endocrinol Metab 2019 Nov 26;32(11):1221-1227. doi: 10.1515/jpem-2019-0188. PMID: 31473686
Makino E, Klodnitsky H, Leonard J, Lillie J, Lund TC, Marshall J, Nietupski J, Orchard PJ, Miller WP, Phaneuf C, Tietz D, Varban ML, Donovan M, Belenki A
Sci Rep 2018 Feb 27;8(1):3681. doi: 10.1038/s41598-018-22078-2. PMID: 29487322Free PMC Article
Grosse SD, Lam WKK, Wiggins LD, Kemper AR
Genet Med 2017 Sep;19(9):975-982. Epub 2017 Jan 26 doi: 10.1038/gim.2016.223. PMID: 28125077Free PMC Article
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA
Arch Dis Child 2009 Jan;94(1):52-4. Epub 2008 May 7 doi: 10.1136/adc.2007.135772. PMID: 18463126

Therapy

Yılmaz Çebi A, Hepokur M
Ophthalmic Genet 2023 Jun;44(3):273-275. Epub 2022 Jul 25 doi: 10.1080/13816810.2022.2103836. PMID: 35876331
Spataro F, Viggiani F, Macchia DG, Rollo V, Tummolo A, Suppressa P, Sabba' C, Rossi MP, Giliberti L, Satriano F, Nettis E, Di Bona D, Caiaffa MF, Fischetto R, Macchia L
Orphanet J Rare Dis 2022 Nov 3;17(1):402. doi: 10.1186/s13023-022-02556-7. PMID: 36329518Free PMC Article
Rodriguez NS, Yanuaria L, Parducho KMR, Garcia IM, Varghese BA, Grubbs BH, Miki T
Stem Cells Transl Med 2017 Jul;6(7):1583-1594. Epub 2017 Jun 6 doi: 10.1002/sctm.16-0449. PMID: 28585336Free PMC Article
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA
Arch Dis Child 2009 Jan;94(1):52-4. Epub 2008 May 7 doi: 10.1136/adc.2007.135772. PMID: 18463126
Connock M, Juarez-Garcia A, Frew E, Mans A, Dretzke J, Fry-Smith A, Moore D
Health Technol Assess 2006 Jun;10(20):iii-iv, ix-113. doi: 10.3310/hta10200. PMID: 16729919

Prognosis

van den Broek BTA, van Egmond-Ebbeling MB, Achterberg JA, Boelens JJ, Vlessert IC, Prinsen HCMT, van Doorn J, van Hasselt PM
Biol Blood Marrow Transplant 2020 May;26(5):928-935. Epub 2019 Nov 29 doi: 10.1016/j.bbmt.2019.11.025. PMID: 31786241
Zahoor MY, Cheema HA, Ijaz S, Anjum MN, Ramzan K, Bhinder MA
J Pediatr Endocrinol Metab 2019 Nov 26;32(11):1221-1227. doi: 10.1515/jpem-2019-0188. PMID: 31473686
Pruszczynski B, Mackenzie WG, Rogers K, White KK
Clin Orthop Relat Res 2015 Oct;473(10):3315-20. Epub 2015 Aug 5 doi: 10.1007/s11999-015-4437-0. PMID: 26242281Free PMC Article
Hollak CE, Weinreb NJ
Best Pract Res Clin Endocrinol Metab 2015 Mar;29(2):205-18. Epub 2014 Aug 27 doi: 10.1016/j.beem.2014.08.006. PMID: 25987174
Murphy AM, Lambert D, Treacy EP, O'Meara A, Lynch SA
Arch Dis Child 2009 Jan;94(1):52-4. Epub 2008 May 7 doi: 10.1136/adc.2007.135772. PMID: 18463126

Clinical prediction guides

Zahoor MY, Cheema HA, Ijaz S, Anjum MN, Ramzan K, Bhinder MA
J Pediatr Endocrinol Metab 2019 Nov 26;32(11):1221-1227. doi: 10.1515/jpem-2019-0188. PMID: 31473686
Vance M, Llanga T, Bennett W, Woodard K, Murlidharan G, Chungfat N, Asokan A, Gilger B, Kurtzberg J, Samulski RJ, Hirsch ML
Sci Rep 2016 Feb 22;6:22131. doi: 10.1038/srep22131. PMID: 26899286Free PMC Article
Pruszczynski B, Mackenzie WG, Rogers K, White KK
Clin Orthop Relat Res 2015 Oct;473(10):3315-20. Epub 2015 Aug 5 doi: 10.1007/s11999-015-4437-0. PMID: 26242281Free PMC Article
Hutchesson AC, Bundey S, Preece MA, Hall SK, Green A
J Med Genet 1998 May;35(5):366-70. doi: 10.1136/jmg.35.5.366. PMID: 9610798Free PMC Article
Walkley SU, Baker HJ
Acta Neuropathol 1984;65(2):138-44. doi: 10.1007/BF00690467. PMID: 6441439

Recent systematic reviews

Connock M, Juarez-Garcia A, Frew E, Mans A, Dretzke J, Fry-Smith A, Moore D
Health Technol Assess 2006 Jun;10(20):iii-iv, ix-113. doi: 10.3310/hta10200. PMID: 16729919

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

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

    Curated

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

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