4obr

Structural highlights

Disease

[IDUA_HUMAN] Hurler-Scheie syndrome;Hurler syndrome;Scheie syndrome. Defects in IDUA are the cause of mucopolysaccharidosis type 1H (MPS1H) [MIM:607014]; also known as Hurler syndrome. MPS1H is a severe form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1H usually present, within the first year of life, a combination of hepatosplenomegaly, skeletal deformities, corneal clouding and severe mental retardation. Obstructive airways disease, respiratory infection and cardiac complications usually result in death before 10 years of age.^{[1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13]} Defects in IDUA are the cause of mucopolysaccharidosis type 1H/S (MPS1H/S) [MIM:607015]; also known as Hurler-Scheie syndrome. MPS1H/S is a form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. MPS1H/S represents an intermediate phenotype of the MPS1 clinical spectrum. It is characterized by relatively little neurological involvement, but most of the somatic symptoms described for severe MPS1 develop in the early to mid-teens, causing considerable loss of mobility. Defects in IDUA are the cause of mucopolysaccharidosis type 1S (MPS1S) [MIM:607016]; also known as Scheie syndrome. MPS1S is a mild form of mucopolysaccharidosis type 1, a rare lysosomal storage disease characterized by progressive physical deterioration with urinary excretion of dermatan sulfate and heparan sulfate. Patients with MPS1S may have little or no neurological involvement, normal stature and life span, but present development of joints stiffness, mild hepatosplenomegaly, aortic valve disease and corneal clouding.

References

1. ↑ Clarke LA, Nelson PV, Warrington CL, Morris CP, Hopwood JJ, Scott HS. Mutation analysis of 19 North American mucopolysaccharidosis type I patients: identification of two additional frequent mutations. Hum Mutat. 1994;3(3):275-82. PMID:8019563 doi:http://dx.doi.org/10.1002/humu.1380030316
2. ↑ Clarke LA, Scott HS. Two novel mutations causing mucopolysaccharidosis type I detected by single strand conformational analysis of the alpha-L-iduronidase gene. Hum Mol Genet. 1993 Aug;2(8):1311-2. PMID:8401515
3. ↑ Bach G, Moskowitz SM, Tieu PT, Matynia A, Neufeld EF. Molecular analysis of Hurler syndrome in Druze and Muslim Arab patients in Israel: multiple allelic mutations of the IDUA gene in a small geographic area. Am J Hum Genet. 1993 Aug;53(2):330-8. PMID:8328452
4. ↑ Scott HS, Litjens T, Nelson PV, Brooks DA, Hopwood JJ, Morris CP. alpha-L-iduronidase mutations (Q70X and P533R) associate with a severe Hurler phenotype. Hum Mutat. 1992;1(4):333-9. PMID:1301941 doi:http://dx.doi.org/10.1002/humu.1380010412
5. ↑ Bunge S, Kleijer WJ, Steglich C, Beck M, Zuther C, Morris CP, Schwinger E, Hopwood JJ, Scott HS, Gal A. Mucopolysaccharidosis type I: identification of 8 novel mutations and determination of the frequency of the two common alpha-L-iduronidase mutations (W402X and Q70X) among European patients. Hum Mol Genet. 1994 Jun;3(6):861-6. PMID:7951228
6. ↑ Tieu PT, Bach G, Matynia A, Hwang M, Neufeld EF. Four novel mutations underlying mild or intermediate forms of alpha-L-iduronidase deficiency (MPS IS and MPS IH/S). Hum Mutat. 1995;6(1):55-9. PMID:7550232 doi:http://dx.doi.org/10.1002/humu.1380060111
7. ↑ Bunge S, Kleijer WJ, Steglich C, Beck M, Schwinger E, Gal A. Mucopolysaccharidosis type I: identification of 13 novel mutations of the alpha-L-iduronidase gene. Hum Mutat. 1995;6(1):91-4. PMID:7550242 doi:http://dx.doi.org/10.1002/humu.1380060119
8. ↑ Scott HS, Anson DS, Orsborn AM, Nelson PV, Clements PR, Morris CP, Hopwood JJ. Human alpha-L-iduronidase: cDNA isolation and expression. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9695-9. PMID:1946389
9. ↑ Lee-Chen GJ, Lin SP, Tang YF, Chin YW. Mucopolysaccharidosis type I: characterization of novel mutations affecting alpha-L-iduronidase activity. Clin Genet. 1999 Jul;56(1):66-70. PMID:10466419
10. ↑ Teng YN, Wang TR, Hwu WL, Lin SP, Lee-Chen GJ. Identification and characterization of -3c-g acceptor splice site mutation in human alpha-L-iduronidase associated with mucopolysaccharidosis type IH/S. Clin Genet. 2000 Feb;57(2):131-6. PMID:10735634
11. ↑ Matte U, Yogalingam G, Brooks D, Leistner S, Schwartz I, Lima L, Norato DY, Brum JM, Beesley C, Winchester B, Giugliani R, Hopwood JJ. Identification and characterization of 13 new mutations in mucopolysaccharidosis type I patients. Mol Genet Metab. 2003 Jan;78(1):37-43. PMID:12559846
12. ↑ Yogalingam G, Guo XH, Muller VJ, Brooks DA, Clements PR, Kakkis ED, Hopwood JJ. Identification and molecular characterization of alpha-L-iduronidase mutations present in mucopolysaccharidosis type I patients undergoing enzyme replacement therapy. Hum Mutat. 2004 Sep;24(3):199-207. PMID:15300847 doi:http://dx.doi.org/10.1002/humu.20081
13. ↑ Bertola F, Filocamo M, Casati G, Mort M, Rosano C, Tylki-Szymanska A, Tuysuz B, Gabrielli O, Grossi S, Scarpa M, Parenti G, Antuzzi D, Dalmau J, Di Rocco M, Vici CD, Okur I, Rosell J, Rovelli A, Furlan F, Rigoldi M, Biondi A, Cooper DN, Parini R. IDUA mutational profiling of a cohort of 102 European patients with mucopolysaccharidosis type I: identification and characterization of 35 novel alpha-L-iduronidase (IDUA) alleles. Hum Mutat. 2011 Jun;32(6):E2189-210. doi: 10.1002/humu.21479. Epub 2011 Mar 10. PMID:21394825 doi:http://dx.doi.org/10.1002/humu.21479