221:
243:. 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).
43:
336:
294:
546:, 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
519:
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
473:
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
439:(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.
327:. 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.
415:(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 (
1134:
1119:
460:
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
426:
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.
284:
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.
876:"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"
457:; 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%.
355:
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.
486:
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.
634:
478:
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.
1391:
1274:
375:(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.
520:
developed unexplained liver tumors. If safety issues can be resolved, gene therapy may provide an alternative human treatment for MPS disorders in the future.
1381:
1401:
1291:
453:
genes and from relatives with similar HLA genes can significantly improve survival, cognitive function, and physical symptoms. Patients can develop
399:
can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.
281:
Airway obstruction is frequent, usually secondary to abnormal cervical vertebrae. Upper and lower respiratory tract infections can be frequent.
1376:
1252:
630:
611:
270:
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
231:
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
228:
Children with Hurler syndrome may appear normal at birth and develop symptoms over the first years of life. Symptoms vary between patients.
1386:
446:
323:
disorder, affected persons have two nonworking copies of the gene. A person born with one normal copy and one defective copy is called a
1267:
1149:
1023:
224:
Corneal clouding in a 30-year-old male with MPS VI. Hurler syndrome and other MPS disorders may also present with corneal clouding.
220:
1260:
205:
554:
refers to MPS II. In 1962, a milder form of MPS I was identified by Scheie, leading to the designation of Scheie syndrome.
142:. The inability to break down these molecules results in a wide variety of symptoms caused by damage to several different
1310:
412:
1345:
581:
1287:
442:
42:
1319:
1013:
420:
309:. This is the gene which encodes for the protein iduronidase. As of 2018, more than 201 different mutations in the
186:
1014:"Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-318 in Subjects With MPS I"
1283:
698:"The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK"
462:
454:
408:
384:
197:
1355:
1160:
1396:
450:
1233:
512:
68:
63:
1295:
185:
appear during childhood, and early death usually occurs. Other, less severe forms of MPS Type I include
111:
80:
874:
Peters C, Shapiro EG, Anderson J, Henslee-Downey PJ, Klemperer MR, Cowan MJ, et al. (April 1998).
254:. These may be present at birth, or they may develop within the first months of life. Clouding of the
531:
527:
523:
1335:
1138:
569:
209:
166:
339:
Heparan sulfate is one of the GAGs that builds up in the lysosomes of people with Hurler syndrome.
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1018:
946:
852:
396:
376:
135:
1200:
1171:
995:
938:
897:
812:
729:
673:
607:
550:, it is likely that she was unaware of his study. Hurler syndrome now refers to MPS IH, while
364:
754:"Hurler syndrome, Hurler-Scheie Syndrome, and Scheie Syndrome (Mucopolysaccharidosis Type I)"
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1074:
985:
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416:
324:
247:
236:
201:
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143:
76:
72:
1049:
343:
The IDUA gene is responsible for encoding an enzyme called alpha-L-iduronidase. Through
990:
965:
807:
788:
776:
724:
697:
656:
Myer CM (July 1991). "Airway obstruction in Hurler's syndrome--radiographic features".
543:
151:
147:
1143:
775:
Chkioua L, Boudabous H, Jaballi I, Grissa O, Turkia HB, Tebib N, Laradi S (May 2018).
1370:
669:
475:
380:
348:
240:
1086:
950:
1350:
1211:
915:
Staba SL, Escolar ML, Poe M, Kim Y, Martin PL, Szabolcs P, et al. (May 2004).
500:
372:
306:
275:
267:
263:
232:
1165:
917:"Cord-blood transplants from unrelated donors in patients with Hurler's syndrome"
777:"Novel splice site IDUA gene mutation in Tunisian pedigrees with hurler syndrome"
363:
Diagnosis often can be made through clinical examination and urine tests (excess
1217:
1195:
547:
503:. In animal models, delivery of the iduronidase gene has been accomplished with
436:
435:
There is currently no cure for Hurler syndrome. Enzyme replacement therapy with
352:
259:
1044:
830:
1247:
1222:
1176:
1128:
981:
797:
508:
504:
344:
335:
892:
875:
449:(UCBT) can be used as treatments for MPS I. BMT from siblings with identical
1206:
320:
317:
155:
87:
999:
942:
816:
733:
714:
293:
1111:
901:
677:
17:
1228:
933:
916:
347:, alpha-L-iduronidase is responsible for breaking down a molecule called
271:
139:
126:
530:, is currently conducting a clinical trial involving gene editing using
262:
may occur within the first year of life, leading to blindness. Enlarged
1078:
516:
182:
173:
responsible for breaking down GAGs. Without this enzyme, a buildup of
1123:
255:
170:
1062:
1063:"Ăśber einen Typ multipler Abartungen, vorwiegend am Skelettsystem"
388:
368:
334:
297:
Hurler syndrome has an autosomal recessive pattern of inheritance.
292:
219:
159:
1154:
392:
301:
Children with Hurler syndrome carry two defective copies of the
1256:
134:
that results in the buildup of large sugar molecules called
696:
Moore D, Connock MJ, Wraith E, Lavery C (September 2008).
407:
All members of the mucopolysaccharidosis family are also
1248:
635:
National
Institute of Neurological Disorders and Stroke
499:
A great deal of interest exists in treating MPS I with
658:
International
Journal of Pediatric Otorhinolaryngology
1101:
1303:
1186:
1105:
604:
96:
86:
62:
54:
35:
305:gene, which has been mapped to the 4p16.3 site on
1268:
8:
165:The underlying mechanism is a deficiency of
58:Deficiency of the alpha-L iduronidase enzyme
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745:
743:
146:systems, including but not limited to the
41:
32:
989:
932:
891:
806:
796:
723:
713:
602:James WD, Berger TG, et al. (2006).
966:"Gene therapy for mucopolysaccharidosis"
964:Ponder KP, Haskins ME (September 2007).
833:. Genetics Home Reference. 11 June 2019
691:
689:
687:
625:
623:
594:
391:either carries a copy of the defective
1392:Syndromes with intellectual disability
204:(MPS II); however, Hunter syndrome is
313:gene have been shown to cause MPS I.
7:
970:Expert Opinion on Biological Therapy
447:umbilical cord blood transplantation
92:Death usually occurs before 12 years
921:The New England Journal of Medicine
196:Hurler syndrome is classified as a
631:"Mucopolysaccharidoses Fact Sheet"
534:(ZFN) for the treatment of MPS I.
395:or is affected with the disorder.
25:
1382:Proteoglycan metabolism disorders
1024:U.S. National Library of Medicine
702:Orphanet Journal of Rare Diseases
246:Other early symptoms may include
1402:Diseases named after discoverers
1356:MPS IX: Hyaluronidase deficiency
349:unsulfated alpha-L-iduronic acid
1346:MPS VI: Maroteaux-Lamy syndrome
1067:Zeitschrift fĂĽr Kinderheilkunde
853:"Mucopolysaccharidosis type I"
316:Because Hurler syndrome is an
200:. It is clinically related to
1:
1377:Autosomal recessive disorders
1336:MPS III: Sanfilippo syndrome
1223:Mucopolysaccharidosis Type I
752:Banikazemi M (12 Oct 2014).
670:10.1016/0165-5876(91)90101-g
413:Mucopolysaccharidosis type I
50:Patient with Hurler syndrome
1387:Syndromes affecting hearing
443:Bone marrow transplantation
208:, while Hurler syndrome is
1418:
1284:Lysosomal storage diseases
409:lysosomal storage diseases
982:10.1517/14712598.7.9.1333
855:. Genetics Home Reference
798:10.1186/s13000-018-0710-3
463:graft versus host disease
455:graft versus host disease
385:chorionic villus sampling
198:lysosomal storage disease
49:
40:
1341:MPS IV: Morquio syndrome
893:10.1182/blood.V91.7.2601
1331:MPS II: Hunter syndrome
1292:carbohydrate metabolism
582:Maroteaux–Lamy syndrome
237:prominent frontal bones
1320:Hurler–Scheie syndrome
715:10.1186/1750-1172-3-24
513:adeno-associated virus
421:Hurler–Scheie syndrome
340:
298:
225:
187:Hurler–Scheie syndrome
69:Hurler-Scheie syndrome
64:Differential diagnosis
1351:MPS VII: Sly syndrome
1296:Mucopolysaccharidoses
606:. Saunders Elsevier.
338:
296:
223:
112:mucopolysaccharidosis
81:mucopolysaccharidoses
934:10.1056/NEJMoa032613
781:Diagnostic Pathology
532:zinc finger nuclease
528:Richmond, California
524:Sangamo Therapeutics
367:are excreted in the
260:retinal degeneration
181:occurs in the body.
1061:Hurler, G. (1919).
570:Sanfilippo syndrome
526:, headquartered in
365:mucopolysaccharides
278:disease may occur.
239:. The skull can be
210:autosomal recessive
167:alpha-L iduronidase
1187:External resources
1079:10.1007/BF02222956
1019:clinicaltrials.gov
397:Genetic counseling
377:Prenatal diagnosis
341:
299:
226:
216:Signs and symptoms
136:glycosaminoglycans
1364:
1363:
1243:
1242:
1045:Hurler's syndrome
613:978-0-7216-2921-6
252:umbilical hernias
233:head can be large
104:
103:
30:Medical condition
16:(Redirected from
1409:
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1103:
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1073:(5–6): 220–234.
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627:
618:
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576:Morquio syndrome
387:can verify if a
175:dermatan sulfate
132:genetic disorder
122:Hurler's disease
109:, also known as
45:
33:
27:Genetic disorder
21:
1417:
1416:
1412:
1411:
1410:
1408:
1407:
1406:
1367:
1366:
1365:
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1324:Scheie syndrome
1316:Hurler syndrome
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1007:
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600:
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564:Hunter syndrome
560:
552:Hunter syndrome
540:
497:
492:
484:
471:
433:
419:) and MPS-IHS (
417:Scheie syndrome
405:
361:
333:
291:
218:
202:Hunter syndrome
191:Scheie syndrome
179:heparan sulfate
152:skeletal system
124:, and formerly
107:Hurler syndrome
77:Hunter syndrome
73:Scheie syndrome
36:Hurler syndrome
31:
28:
23:
22:
15:
12:
11:
5:
1415:
1413:
1405:
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1399:
1397:Rare syndromes
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1389:
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1106:Classification
1099:
1098:External links
1096:
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1092:
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1036:
1005:
976:(9): 1333–45.
956:
927:(19): 1960–9.
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789:BioMed Central
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544:Gertrud Hurler
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403:Classification
401:
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217:
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189:(MPS-IHS) and
148:nervous system
102:
101:
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1288:Inborn errors
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1097:
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1051:
1050:Who Named It?
1047:
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1040:
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1021:
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1001:
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987:
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940:
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930:
926:
922:
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911:
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903:
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894:
889:
886:(7): 2601–8.
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870:
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854:
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832:
826:
823:
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755:
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731:
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637:. 15 Nov 2017
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489:
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479:
477:
476:survival rate
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448:
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430:
428:
424:
422:
418:
414:
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402:
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394:
390:
386:
382:
381:amniocentesis
378:
374:
373:Enzyme assays
370:
366:
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356:
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346:
337:
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326:
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34:
19:
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1205:
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1159:
1148:
1133:
1118:
1070:
1066:
1056:
1043:
1039:
1027:. Retrieved
1017:
1008:
973:
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959:
924:
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910:
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869:
857:. Retrieved
847:
835:. Retrieved
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758:. Retrieved
705:
701:
661:
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651:
639:. Retrieved
603:
597:
541:
522:
501:gene therapy
498:
495:Gene therapy
485:
482:Epidemiology
472:
459:
441:
434:
425:
406:
362:
351:. This is a
342:
315:
310:
307:chromosome 4
302:
300:
283:
280:
276:Aortic valve
245:
230:
227:
195:
164:
125:
121:
117:
110:
106:
105:
100:1 in 100,000
1218:GeneReviews
1196:MedlinePlus
831:"IDUA gene"
664:(1): 91–6.
548:World War I
437:iduronidase
353:uronic acid
1371:Categories
1304:Catabolism
1172:DiseasesDB
1029:7 February
756:. Medscape
589:References
509:adenovirus
505:retrovirus
445:(BMT) and
345:hydrolysis
331:Mechanisms
193:(MPS-IS).
138:(GAGs) in
127:gargoylism
18:Gargoylism
1207:eMedicine
572:(MPS III)
542:In 1919,
469:Prognosis
431:Treatment
359:Diagnosis
321:recessive
318:autosomal
241:elongated
140:lysosomes
97:Frequency
88:Prognosis
1229:Orphanet
1212:ped/1031
1087:34471544
1000:17727324
951:43572313
943:15128896
817:29843745
734:18796143
584:(MPS VI)
578:(MPS IV)
566:(MPS II)
558:See also
490:Research
289:Genetics
272:diarrhea
248:inguinal
206:X-linked
183:Symptoms
79:; other
1166:D008059
991:3340574
902:9516162
837:18 June
808:5975427
725:2553763
678:1917344
538:History
517:plasmid
325:carrier
130:, is a
114:Type IH
1201:001204
1155:607014
1085:
998:
988:
949:
941:
900:
859:10 May
815:
805:
791:: 35.
760:10 May
732:
722:
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676:
641:11 May
610:
515:, and
379:using
268:spleen
256:cornea
171:enzyme
158:, and
118:MPS-IH
55:Causes
1311:MPS I
1234:93473
1144:277.5
1129:E76.0
1083:S2CID
947:S2CID
880:Blood
787:(1).
389:fetus
369:urine
264:liver
235:with
169:, an
160:heart
144:organ
1177:6067
1161:MeSH
1150:OMIM
1139:9-CM
1031:2019
996:PMID
939:PMID
898:PMID
861:2018
839:2019
813:PMID
762:2018
730:PMID
674:PMID
643:2018
608:ISBN
393:gene
383:and
311:IDUA
303:IDUA
266:and
258:and
250:and
177:and
156:eyes
1290:of
1135:ICD
1120:ICD
1075:doi
1048:at
986:PMC
978:doi
929:doi
925:350
888:doi
803:PMC
793:doi
720:PMC
710:doi
666:doi
451:HLA
423:).
371:).
120:),
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