Mucopolysaccharidosis VI.
Mucopolysaccharidosis VI (MPS VI) is a lysosomal storage disease with progressive multisystem involvement, associated with a deficiency of arylsulfatase B leading to the accumulation of dermatan sulfate. Birth prevalence is between 1 in 43,261 and 1 in 1,505,160 live births. The disorder shows a wide spectrum of symptoms from slowly to rapidly progressing forms. The characteristic skeletal dysplasia includes short stature, dysostosis multiplex and degenerative joint disease. Rapidly progressing forms may have onset from birth, elevated urinary glycosaminoglycans (generally >100 microg/mg creatinine), severe dysostosis multiplex, short stature, and death before the 2nd or 3rd decades. A more slowly progressing form has been described as having later onset, mildly elevated glycosaminoglycans (generally <100 microg/mg creatinine), mild dysostosis multiplex, with death in the 4th or 5th decades. Other clinical findings may include cardiac valve disease, reduced pulmonary function, hepatosplenomegaly, sinusitis, otitis media, hearing loss, sleep apnea, corneal clouding, carpal tunnel disease, and inguinal or umbilical hernia. Although intellectual deficit is generally absent in MPS VI, central nervous system findings may include cervical cord compression caused by cervical spinal instability, meningeal thickening and/or bony stenosis, communicating hydrocephalus, optic nerve atrophy and blindness. The disorder is transmitted in an autosomal recessive manner and is caused by mutations in the ARSB gene, located in chromosome 5 (5q13-5q14). Over 130 ARSB mutations have been reported, causing absent or reduced arylsulfatase B (N-acetylgalactosamine 4-sulfatase) activity and interrupted dermatan sulfate and chondroitin sulfate degradation. Diagnosis generally requires evidence of clinical phenotype, arylsulfatase B enzyme activity <10% of the lower limit of normal in cultured fibroblasts or isolated leukocytes, and demonstration of a normal activity of a different sulfatase enzyme (to exclude multiple sulfatase deficiency). The finding of elevated urinary dermatan sulfate with the absence of heparan sulfate is supportive. In addition to multiple sulfatase deficiency, the differential diagnosis should also include other forms of MPS (MPS I, II IVA, VII), sialidosis and mucolipidosis. Before enzyme replacement therapy (ERT) with galsulfase (Naglazyme), clinical management was limited to supportive care and hematopoietic stem cell transplantation. Galsulfase is now widely available and is a specific therapy providing improved endurance with an acceptable safety profile. Prognosis is variable depending on the age of onset, rate of disease progression, age at initiation of ERT and on the quality of the medical care provided.
Valayannopoulos
Vassili
V
Reference Center for Inherited Metabolic Diseases, Necker-Enfants Malades Hospital, Paris, France.
Nicely
Helen
H
Harmatz
Paul
P
Turbeville
Sean
S
D006801:Humans; D009087:Mucopolysaccharidosis VI / Q000175:diagnosis* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D020051:N-Acetylgalactosamine-4-Sulfatase / Q000378:metabolism
D020051:N-Acetylgalactosamine-4-Sulfatase
Eur J Pediatr. 1995 Feb;154(2):98-101
7720756
Glycobiology. 2002 Sep;12(9):117R-25R
12213784
Bone Marrow Transplant. 1992;10 Suppl 1:87-96
1521098
Hum Genet. 1997 Dec;101(3):355-8
9439667
Acta Cardiol. 2005 Feb;60(1):51-3
15779852
Acta Radiol. 2002 Jan;43(1):40-3
11972460
Hum Mutat. 2004 Mar;23(3):229-33
14974081
Clin Genet. 1986 Nov;30(5):409-15
3100114
J Med Genet. 1991 Jul;28(7):499-501
1832719
Am J Hum Genet. 1991 Apr;48(4):710-9
1901688
J Inherit Metab Dis. 2005;28(6):1011-7
16435194
J Biol Chem. 1996 Nov 1;271(44):27259-65
8910299
Pediatrics. 2008 Mar;121(3):e714-7
18250117
J Inherit Metab Dis. 2010 Feb;33(1):51-60
20140523
Anaesth Intensive Care. 1983 Aug;11(3):198-202
6412587
Am J Pathol. 2008 Jan;172(1):112-22
18079441
Am J Med Genet A. 2005 Apr 15;134A(2):144-50
15690405
Hum Mutat. 2001 Oct;18(4):282-95
11668612
Acta Paediatr Jpn. 1994 Feb;36(1):30-6
8165905
Am J Hum Genet. 1994 Mar;54(3):454-63
8116615
Acta Paediatr Taiwan. 2001 Sep-Oct;42(5):306-8
11729709
Helv Paediatr Acta. 1970 Oct;25(4):337-62
4250491
Mol Genet Metab. 2008 Jul;94(3):305-12
18406185
Hum Mutat. 2007 Sep;28(9):897-903
17458871
Arq Neuropsiquiatr. 2006 Mar;64(1):1-4
16622543
Clin Chem. 2004 Oct;50(10):1785-96
15292070
J Clin Invest. 1996 Apr 15;97(8):1864-73
8621770
Pediatrics. 2005 Jun;115(6):e681-9
15930196
Mol Genet Metab. 2006 Aug;88(4):307-14
16600651
Mol Genet Metab. 2007 Aug;91(4):352-61
17544310
Hum Mutat. 1996;7(4):361-3
8723688
Ann Neurol. 1979 Oct;6(4):315-25
122048
Pediatr Cardiol. 1983 Jan-Mar;4(1):61-2
6405371
Am J Med Genet A. 2003 Dec 15;123A(3):310-3
14608657
J Inherit Metab Dis. 2008 Dec;31(6):733-7
18923918
Clin Chem. 2007 Jan;53(1):137-40
17082248
Biochem J. 1987 Dec 15;248(3):755-64
3435483
J Infus Nurs. 2009 Jan-Feb;32(1):45-52
19142150
Am J Hum Genet. 1992 Apr;50(4):795-800
1550123
Mol Genet Metab. 2007 May;91(1):61-8
17321776
J Biol Chem. 1991 Nov 15;266(32):21386-91
1718978
J Clin Invest. 1998 Jan 1;101(1):109-19
9421472
Eur J Pediatr. 1997 Aug;156(8):650-4
9266201
Genetika. 2000 Jun;36(6):837-43
10923267
Hastings Cent Rep. 2008 May-Jun;38(3):32-9
18581935
Neurology. 2007 Aug 28;69(9):917-24
17724296
Hum Mutat. 1992;1(5):397-402
1301949
Acta Paediatr Suppl. 2005 Mar;94(447):61-8; discussion 57
15895715
J Pediatr. 2004 May;144(5):574-80
15126989
Can J Anaesth. 1988 Sep;35(5):540-1
3139312
N Engl J Med. 1984 Dec 20;311(25):1606-11
6150438
Arch Ophthalmol. 1998 Mar;116(3):400
9514506
Arthritis Rheum. 2003 Aug;48(8):2163-72
12905469
Acta Paediatr. 2008 Apr;97(457):33-7
18339185
Mol Genet Metab. 2005 Jul;85(3):236-8
15979036
J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):397-404
16763908
Clin Genet. 2004 Sep;66(3):208-13
15324318
Genet Test. 2003 Winter;7(4):347-9
15000815
Mol Genet Metab. 2010 Apr;99(4):346-50
20036175
Pediatrics. 2000 Jan;105(1):e10
10617747
Genet Couns. 1995;6(1):43-7
7794561
Am J Hum Genet. 1996 Jun;58(6):1127-34
8651289
Am J Med Genet A. 2008 Oct 1;146A(19):2538-44
18792977
Hum Genet. 1999 Jul-Aug;105(1-2):151-6
10480370
Pediatrics. 2007 Aug;120(2):405-18
17671068
J Pediatr. 2002 Mar;140(3):321-7
11953730
Clin Chim Acta. 2006 Oct;372(1-2):98-102
16712827
Eur J Hum Genet. 2004 Feb;12(2):87-92
14685153
Medicine (Baltimore). 1988 Jul;67(4):209-19
3134589
Clin Genet. 1987 Feb;31(2):114-7
3103957
Int Ophthalmol. 2009 Aug;29(4):267-9
18418554
Lab Invest. 2001 Sep;81(9):1319-28
11555679
Biochem J. 1986 Mar 15;234(3):507-14
3087346
Hum Genet. 1989 Apr;82(1):67-8
2714781
Pediatr Res. 2006 Apr;59(4 Pt 1):538-43
16549525
J Med Genet. 1978 Dec;15(6):455-61
106124
Int J Pediatr Otorhinolaryngol. 2005 May;69(5):589-95
15850680
Clin Chim Acta. 2005 Mar;353(1-2):67-74
15698592
Lancet. 1995 Jun 3;345(8962):1398-402
7760610
Brain Dev. 2008 May;30(5):374-7
18509892
Pediatr Res. 2004 Apr;55(4):585-91
14711884
Clin Genet. 2010 May;77(5):492-8
19968667
J Pediatr. 2006 Apr;148(4):533-539
16647419
Mol Genet Metab. 2009 Jul;97(3):234-6
19427803
Circulation. 1992 Jan;85(1):188-95
1728449
Birth Defects Orig Artic Ser. 1971 Mar;7(3):32-40
5006141
Hum Genet. 1990 Aug;85(3):389-90
2118475
Clin Chim Acta. 2006 Dec;374(1-2):171-2
16949067
Acta Paediatr. 2008 Nov;97(11):1577-81
18681890
Genome Res. 2005 Nov;15(11):1592-3
16251469
Surv Ophthalmol. 2006 Jan-Feb;51(1):1-17
16414358
J Pediatr (Rio J). 2008 Mar-Apr;84(2):130-5
18338089
Clin Chem. 2008 Oct;54(10):1725-8
18719200
Bone Marrow Transplant. 2008 Jun;41 Suppl 2:S87-9
18545253
Br J Radiol. 1982 Nov;55(659):805-12
6814560
J Pediatr. 1992 Feb;120(2 Pt 1):269-72
1735826
Clin Chim Acta. 2008 Aug;394(1-2):89-93
18486607
Mol Genet Metab. 2003 Mar;78(3):163-74
12649061
J Inherit Metab Dis. 2005;28(6):1027-34
16435196
Presse Med. 1963 Sep 25;71:1849-52
14091597
Mol Genet Metab. 2008 Aug;94(4):469-75
18502162
World J Pediatr. 2008 May;4(2):152-4
18661775
Pediatr Res. 2005 May;57(5 Pt 1):701-7
15746260
Curr Opin Neurol. 1999 Apr;12(2):167-76
10226749
Pediatr Neurosurg. 2001 Jul;35(1):35-8
11490189
J Inherit Metab Dis. 1999 Feb;22(1):50-62
10070618
Eur J Hum Genet. 2009 Sep;17(9):1160-4
19259130
J Clin Invest. 1997 Feb 15;99(4):651-62
9045867
J Inherit Metab Dis. 2007 Apr;30(2):165-74
17347914