210:
232:. The nose can have a flattened nasal bridge with continuous nasal discharge. The eye sockets may be widely spaced, and the eyes may protrude from the skull. The lips can be large, and affected children may hold their jaws open constantly. Skeletal abnormalities occur by about age 6 months, but may not be clinically obvious until 10–14 months. Patients may experience debilitating spine and hip deformities, carpal tunnel syndrome, and joint stiffness. Patients may be normal height in infancy, but stop growing by the age of two years. They may not reach a height of greater than 4 ft (1.2 m).
32:
325:
283:
535:, a German pediatrician, described a syndrome involving corneal clouding, skeletal abnormalities, and mental retardation. A similar disease of "gargoylism" had been described in 1917 by Charles A. Hunter. Hurler did not mention Hunter's paper. Because of the communications interruptions caused by
508:
vectors. Mice and dogs with MPS I have been successfully treated with gene therapy. Most vectors can correct the disease in the liver and spleen, and can correct brain effects with a high dosage. Gene therapy has improved survival, neurological, and physical symptoms; however, some animals have
462:
A British study from 2008 found a median estimated life expectancy of 8.7 years for patients with Hurler syndrome. In comparison, the median life expectancy for all forms of MPS type I was 11.6 years. Patients who received successful bone marrow transplants had a 2-year
428:(Aldurazyme) may improve pulmonary function and mobility. It can reduce the amount of carbohydrates being improperly stored in organs. Surgical correction of hand and foot deformities may be necessary. Corneal surgery may help alleviate vision problems.
316:. They will produce less α-L-iduronidase than an individual with two normal copies of the gene. The reduced production of the enzyme in carriers, however, remains sufficient for normal function; the person should not show any symptoms of the disease.
404:(MPS I) is divided into three subtypes based on severity of symptoms. All three types result the absence or decreased functioning of the same enzyme. MPS-IH (Hurler syndrome) is the most severe of the MPS I subtypes. The other two types are MPS-IS (
1123:
1108:
449:
Children often lack access to a suitable bone marrow donor. In these cases, UCBT from unrelated donors can increase survival, decrease physical signs of the disease, and improve cognition. Complications from this treatment may include
415:
Because of the substantial overlap between Hurler syndrome, Hurler–Scheie syndrome, and Scheie syndrome, some sources consider these terms to be outdated. Instead, MPS I may be divided into "severe" and "attenuated" forms.
273:
Developmental delay may become apparent by age 1–2 years, with a maximum functional age of 2–4 years. Progressive deterioration follows. Most children develop limited language capabilities. Death usually occurs by age 10.
865:"Hurler syndrome: II. Outcome of HLA-genotypically identical sibling and HLA-haploidentical related donor bone marrow transplantation in fifty-four children. The Storage Disease Collaborative Study Group"
446:; this is more likely in non-sibling donors. In a 1998 study, children with HLA-identical sibling donors had a five-year survival of 75%; children with non-sibling donors had a five-year survival of 53%.
344:
found in the GAGs dermatan sulfate and heparan sulfate. The alpha-L-iduronidase enzyme is located in lysosomes. Without sufficient enzymatic function, these GAGs cannot be digested properly.
475:
Hurler syndrome has an overall frequency of one per 100,000. Combined, all of the mucopolysaccharidoses have a frequency of approximately one in every 25,000 births in the United States.
623:
467:
of 68% and a 10-year survival rate of 64%. Patients who did not receive bone marrow transplants had a significantly reduced lifespan, with a median age of 6.8 years.
1380:
1263:
364:(testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses.
509:
developed unexplained liver tumors. If safety issues can be resolved, gene therapy may provide an alternative human treatment for MPS disorders in the future.
1370:
1390:
1280:
442:
genes and from relatives with similar HLA genes can significantly improve survival, cognitive function, and physical symptoms. Patients can develop
388:
can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.
270:
Airway obstruction is frequent, usually secondary to abnormal cervical vertebrae. Upper and lower respiratory tract infections can be frequent.
1365:
1241:
619:
600:
259:
are common. There is no organ dysfunction, but GAG deposition in these organs may lead to a massive increase in size. Patients may also have
220:
One of the first abnormalities that may be detected is coarsening of the facial features; these symptoms can begin at 3–6 months of age. The
217:
Children with Hurler syndrome may appear normal at birth and develop symptoms over the first years of life. Symptoms vary between patients.
1375:
435:
312:
disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a
1256:
1138:
1012:
213:
Corneal clouding in a 30-year-old male with MPS VI. Hurler syndrome and other MPS disorders may also present with corneal clouding.
209:
1249:
194:
543:
refers to MPS II. In 1962, a milder form of MPS I was identified by Scheie, leading to the designation of Scheie syndrome.
131:. The inability to break down these molecules results in a wide variety of symptoms caused by damage to several different
1299:
401:
1334:
570:
1276:
431:
31:
1308:
1002:
409:
298:. This is the gene which encodes for the protein iduronidase. As of 2018, more than 201 different mutations in the
175:
1003:"Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I"
1272:
687:"The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK"
451:
443:
397:
373:
186:
1344:
1149:
1385:
439:
1222:
501:
57:
52:
1284:
174:
appear during childhood, and early death usually occurs. Other, less severe forms of MPS Type I include
100:
69:
863:
Peters C, Shapiro EG, Anderson J, Henslee-Downey PJ, Klemperer MR, Cowan MJ, et al. (April 1998).
243:. These may be present at birth, or they may develop within the first months of life. Clouding of the
520:
516:
512:
1324:
1127:
558:
198:
155:
328:
Heparan sulfate is one of the GAGs that builds up in the lysosomes of people with Hurler syndrome.
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1007:
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385:
365:
124:
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984:
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718:
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539:, it is likely that she was unaware of his study. Hurler syndrome now refers to MPS IH, while
353:
743:"Hurler syndrome, Hurler-Scheie Syndrome, and Scheie Syndrome (Mucopolysaccharidosis Type I)"
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132:
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61:
1038:
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The IDUA gene is responsible for encoding an enzyme called alpha-L-iduronidase. Through
979:
954:
796:
777:
765:
713:
686:
645:
Myer CM (July 1991). "Airway obstruction in Hurler's syndrome--radiographic features".
532:
140:
136:
1132:
764:
Chkioua L, Boudabous H, Jaballi I, Grissa O, Turkia HB, Tebib N, Laradi S (May 2018).
1359:
658:
464:
369:
337:
229:
1075:
939:
1339:
1200:
904:
Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, et al. (May 2004).
489:
361:
295:
264:
256:
252:
221:
1154:
906:"Cord-blood transplants from unrelated donors in patients with Hurler's syndrome"
766:"Novel splice site IDUA gene mutation in Tunisian pedigrees with hurler syndrome"
352:
Diagnosis often can be made through clinical examination and urine tests (excess
1206:
1184:
536:
492:. In animal models, delivery of the iduronidase gene has been accomplished with
425:
424:
There is currently no cure for Hurler syndrome. Enzyme replacement therapy with
341:
248:
1033:
819:
1236:
1211:
1165:
1117:
970:
786:
497:
493:
333:
324:
881:
864:
438:(UCBT) can be used as treatments for MPS I. BMT from siblings with identical
1195:
309:
306:
144:
76:
988:
931:
805:
722:
703:
282:
1100:
890:
666:
1217:
922:
905:
336:, alpha-L-iduronidase is responsible for breaking down a molecule called
260:
128:
115:
519:, is currently conducting a clinical trial involving gene editing using
251:
may occur within the first year of life, leading to blindness. Enlarged
1067:
505:
171:
162:
responsible for breaking down GAGs. Without this enzyme, a buildup of
1112:
244:
159:
1051:
1052:"Ăśber einen Typ multipler Abartungen, vorwiegend am Skelettsystem"
377:
357:
323:
286:
Hurler syndrome has an autosomal recessive pattern of inheritance.
281:
208:
148:
1143:
381:
290:
Children with Hurler syndrome carry two defective copies of the
1245:
123:
that results in the buildup of large sugar molecules called
685:
Moore D, Connock MJ, Wraith E, Lavery C (September 2008).
396:
All members of the mucopolysaccharidosis family are also
1237:
624:
National
Institute of Neurological Disorders and Stroke
488:
A great deal of interest exists in treating MPS I with
647:
International
Journal of Pediatric Otorhinolaryngology
1090:
1292:
1175:
1094:
593:
85:
75:
51:
43:
24:
294:gene, which has been mapped to the 4p16.3 site on
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8:
154:The underlying mechanism is a deficiency of
47:Deficiency of the alpha-L iduronidase enzyme
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732:
135:systems, including but not limited to the
30:
21:
978:
921:
880:
795:
785:
712:
702:
591:James WD, Berger TG, et al. (2006).
955:"Gene therapy for mucopolysaccharidosis"
953:Ponder KP, Haskins ME (September 2007).
822:. Genetics Home Reference. 11 June 2019
680:
678:
676:
614:
612:
583:
380:either carries a copy of the defective
1381:Syndromes with intellectual disability
193:(MPS II); however, Hunter syndrome is
302:gene have been shown to cause MPS I.
7:
959:Expert Opinion on Biological Therapy
436:umbilical cord blood transplantation
81:Death usually occurs before 12 years
910:The New England Journal of Medicine
185:Hurler syndrome is classified as a
620:"Mucopolysaccharidoses Fact Sheet"
523:(ZFN) for the treatment of MPS I.
384:or is affected with the disorder.
14:
1371:Proteoglycan metabolism disorders
1013:U.S. National Library of Medicine
691:Orphanet Journal of Rare Diseases
235:Other early symptoms may include
1391:Diseases named after discoverers
1345:MPS IX: Hyaluronidase deficiency
338:unsulfated alpha-L-iduronic acid
1335:MPS VI: Maroteaux-Lamy syndrome
1056:Zeitschrift fĂĽr Kinderheilkunde
842:"Mucopolysaccharidosis type I"
305:Because Hurler syndrome is an
189:. It is clinically related to
1:
1366:Autosomal recessive disorders
1325:MPS III: Sanfilippo syndrome
1212:Mucopolysaccharidosis Type I
741:Banikazemi M (12 Oct 2014).
659:10.1016/0165-5876(91)90101-g
402:Mucopolysaccharidosis type I
39:Patient with Hurler syndrome
1376:Syndromes affecting hearing
432:Bone marrow transplantation
197:, while Hurler syndrome is
1407:
1273:Lysosomal storage diseases
398:lysosomal storage diseases
971:10.1517/14712598.7.9.1333
844:. Genetics Home Reference
787:10.1186/s13000-018-0710-3
452:graft versus host disease
444:graft versus host disease
374:chorionic villus sampling
187:lysosomal storage disease
38:
29:
1330:MPS IV: Morquio syndrome
882:10.1182/blood.V91.7.2601
1320:MPS II: Hunter syndrome
1281:carbohydrate metabolism
571:Maroteaux–Lamy syndrome
226:prominent frontal bones
1309:Hurler–Scheie syndrome
704:10.1186/1750-1172-3-24
502:adeno-associated virus
410:Hurler–Scheie syndrome
329:
287:
214:
176:Hurler–Scheie syndrome
58:Hurler-Scheie syndrome
53:Differential diagnosis
1340:MPS VII: Sly syndrome
1285:Mucopolysaccharidoses
595:. Saunders Elsevier.
327:
285:
212:
101:mucopolysaccharidosis
70:mucopolysaccharidoses
923:10.1056/NEJMoa032613
770:Diagnostic Pathology
521:zinc finger nuclease
517:Richmond, California
513:Sangamo Therapeutics
356:are excreted in the
249:retinal degeneration
170:occurs in the body.
1050:Hurler, G. (1919).
559:Sanfilippo syndrome
515:, headquartered in
354:mucopolysaccharides
267:disease may occur.
228:. The skull can be
199:autosomal recessive
156:alpha-L iduronidase
1176:External resources
1068:10.1007/BF02222956
1008:clinicaltrials.gov
386:Genetic counseling
366:Prenatal diagnosis
330:
288:
215:
205:Signs and symptoms
125:glycosaminoglycans
1353:
1352:
1232:
1231:
1034:Hurler's syndrome
602:978-0-7216-2921-6
241:umbilical hernias
222:head can be large
93:
92:
19:Medical condition
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1080:
1079:
1062:(5–6): 220–234.
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631:
616:
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565:Morquio syndrome
376:can verify if a
164:dermatan sulfate
121:genetic disorder
111:Hurler's disease
98:, also known as
34:
22:
16:Genetic disorder
1406:
1405:
1401:
1400:
1399:
1397:
1396:
1395:
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1313:Scheie syndrome
1305:Hurler syndrome
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1103:
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585:
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553:Hunter syndrome
549:
541:Hunter syndrome
529:
486:
481:
473:
460:
422:
408:) and MPS-IHS (
406:Scheie syndrome
394:
350:
322:
280:
207:
191:Hunter syndrome
180:Scheie syndrome
168:heparan sulfate
141:skeletal system
113:, and formerly
96:Hurler syndrome
66:Hunter syndrome
62:Scheie syndrome
25:Hurler syndrome
20:
17:
12:
11:
5:
1404:
1402:
1394:
1393:
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1386:Rare syndromes
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1378:
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1095:Classification
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1087:External links
1085:
1082:
1081:
1042:
1025:
994:
965:(9): 1333–45.
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916:(19): 1960–9.
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778:BioMed Central
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533:Gertrud Hurler
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392:Classification
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349:
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178:(MPS-IHS) and
137:nervous system
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55:
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1277:Inborn errors
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1086:
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1040:
1039:Who Named It?
1036:
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990:
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937:
933:
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919:
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888:
883:
878:
875:(7): 2601–8.
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626:. 15 Nov 2017
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465:survival rate
457:
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419:
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411:
407:
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379:
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371:
370:amniocentesis
367:
363:
362:Enzyme assays
359:
355:
347:
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343:
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326:
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50:
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37:
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28:
23:
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1122:
1107:
1059:
1055:
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1032:
1028:
1016:. Retrieved
1006:
997:
962:
958:
948:
913:
909:
899:
872:
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846:. Retrieved
836:
824:. Retrieved
814:
773:
769:
759:
747:. Retrieved
694:
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650:
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640:
628:. Retrieved
592:
586:
530:
511:
490:gene therapy
487:
484:Gene therapy
474:
471:Epidemiology
461:
448:
430:
423:
414:
395:
351:
340:. This is a
331:
304:
299:
296:chromosome 4
291:
289:
272:
269:
265:Aortic valve
234:
219:
216:
184:
153:
114:
110:
106:
99:
95:
94:
89:1 in 100,000
1207:GeneReviews
1185:MedlinePlus
820:"IDUA gene"
653:(1): 91–6.
537:World War I
426:iduronidase
342:uronic acid
1360:Categories
1293:Catabolism
1161:DiseasesDB
1018:7 February
745:. Medscape
578:References
498:adenovirus
494:retrovirus
434:(BMT) and
334:hydrolysis
320:Mechanisms
182:(MPS-IS).
127:(GAGs) in
116:gargoylism
1196:eMedicine
561:(MPS III)
531:In 1919,
458:Prognosis
420:Treatment
348:Diagnosis
310:recessive
307:autosomal
230:elongated
129:lysosomes
86:Frequency
77:Prognosis
1218:Orphanet
1201:ped/1031
1076:34471544
989:17727324
940:43572313
932:15128896
806:29843745
723:18796143
573:(MPS VI)
567:(MPS IV)
555:(MPS II)
547:See also
479:Research
278:Genetics
261:diarrhea
237:inguinal
195:X-linked
172:Symptoms
68:; other
1155:D008059
980:3340574
891:9516162
826:18 June
797:5975427
714:2553763
667:1917344
527:History
506:plasmid
314:carrier
119:, is a
103:Type IH
1190:001204
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368:using
257:spleen
245:cornea
160:enzyme
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107:MPS-IH
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1300:MPS I
1223:93473
1133:277.5
1118:E76.0
1072:S2CID
936:S2CID
869:Blood
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378:fetus
358:urine
253:liver
224:with
158:, an
149:heart
133:organ
1166:6067
1150:MeSH
1139:OMIM
1128:9-CM
1020:2019
985:PMID
928:PMID
887:PMID
850:2018
828:2019
802:PMID
751:2018
719:PMID
663:PMID
632:2018
597:ISBN
382:gene
372:and
300:IDUA
292:IDUA
255:and
247:and
239:and
166:and
145:eyes
1279:of
1124:ICD
1109:ICD
1064:doi
1037:at
975:PMC
967:doi
918:doi
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655:doi
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