39:
63:
415:. The first step in the breakdown of dermatan sulfate and heparan sulfate requires the lysosomal enzyme iduronate-2-sulfatase, or I2S. In people with MPS II, this enzyme is either partially or completely inactive. As a result, GAGs build up in cells throughout the body, particularly in tissues that contain large amounts of dermatan sulfate and heparan sulfate. The rate of GAGs buildup is not the same for all people with MPS II, resulting in a wide spectrum of medical problems.
318:, although the existence and level of symptoms differ in each affected child. They often also include a lack of an appropriate sense of danger, and aggression. The behavioral symptoms of MPS II generally precede neurodegeneration and often increase in severity until the mental handicaps become more pronounced. By the time of death, most children with severe MPS II have severe mental disabilities and are completely dependent on their caretakers.
327:
366:
530:(HSCT) have been used as treatments in some studies. While transplantation has provided benefits for many organ systems, it has not been shown to improve the neurological symptoms of the disease. Although HSCT has shown promise in the treatment of other MPS disorders, its results have been unsatisfactory so far in the treatment of MPS II. ERT has been shown to lead to better outcomes in MPS II patients.
1385:
353:. A male who inherits a defective X chromosome, though, usually does not have another X chromosome to compensate for the mutant gene. Thus, a female would need to inherit two mutant genes to develop MPS II, while a male patient only needs to inherit one mutant gene. A female carrier can be affected due to
249:
The continued storage of GAGs leads to abnormalities in multiple organ systems. After 18 months, children with severe MPS II may experience developmental decline and progressive loss of skills. The thickening of the heart valves and walls of the heart can result in progressive decline in cardiac
214:
symptoms, but this is an oversimplification. Patients with "attenuated" or "mild" forms of the disease may still have significant health issues. For severely affected patients, the clinical course is relatively predictable; patients will normally die at an early age. For those with milder forms of
566:
Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients
598:
injections of a more concentrated dose of idursulfase than the intravenous formulation used in enzyme replacement therapy infusions, in hopes of preventing the cognitive decline associated with the severe form of the condition. Results were reported in
October 2013. A phase II/III clinical trial
635:
by reason of diminished capacity. Mrs
Justice Anne Rafferty called the case "exceptional", gave Wragg a two-year prison sentence for manslaughter, then suspended his sentence for two years. Rafferty said "nothing to be gained" from sending Wragg to prison for the crime.
400:. It helps to form the architectural framework of the body. The matrix surrounds the cells of the body in an organized meshwork and functions as the glue that holds the cells of the body together. One of the parts of the extracellular matrix is a molecule called a
1200:"A Safety and Dose Ranging Study of Idursulfase (Intrathecal) Administration Via an Intrathecal Drug Delivery Device in Pediatric Patients With Hunter Syndrome Who Have Central Nervous System Involvement and Are Receiving Treatment With Elaprase® - Results"
230:. As the buildup of GAGs continues throughout the cells of the body, signs of MPS II become more visible. The physical appearance of many children with the syndrome include a distinctive coarseness in their facial features, including a prominent
882:
Muenzer, J; Wraith, JE; Beck, M; Giugliani, R; Harmatz, P; Eng, CM; Vellodi, A; Martin, R; Ramaswami, U; Gucsavas-Calikoglu, M; Vijayaraghavan, S; Wendt, S; Puga, AC; Ulbrich, B; Shinawi, M; Cleary, M; Piper, D; Conway, AM; Kimura, A (August 2006).
514:(ERT) with idursulfase have been proven to improve many signs and symptoms of MPS II, especially if started early in the disease. After administration, it can be transported into cells to break down GAGs, but as the medication cannot cross the
215:
the disease, a wider variety of outcomes exist. Many live into their 20s and 30s, but some may have near-normal life expectancies. Cardiac and respiratory abnormalities are the usual cause of death for patients with milder forms of the disease.
198:. It causes abnormalities in many organs, including the skeleton, heart, and respiratory system. In severe cases, this leads to death during the teenaged years. Unlike MPS I, corneal clouding is not associated with this disease.
301:
The age at onset of symptoms and the presence or absence of behavioral disturbances are predictive factors of ultimate disease severity in very young patients. Behavioral disturbances can often mimic combinations of symptoms of
1174:"A Phase I/II, Randomized, Safety and Ascending Dose Ranging Study of Intrathecal Idursulfase-IT Administered in Conjunction With Intravenous Elaprase in Pediatric Patients With Hunter Syndrome and Cognitive Impairment"
518:, it is not expected to lead to cognitive improvement in patients with severe central nervous system symptoms. Even with ERT, treatment of various organ problems from a wide variety of medical specialists is necessary.
1433:
1418:
967:
Annibali, R (October 2013). "Hunter syndrome (Mucopolysaccharidosis type II), severe phenotype: long term follow-up on patients undergone to hematopoietic stem cell transplantation". Vol. 65, no. 5.
338:
gene is located on the X chromosome. The IDS gene encodes for an enzyme called iduronate-2-sulfatase (I2S). A lack of this enzyme leads to a buildup of GAGs, which cause the symptoms of MPS II.
242:, as well as an enlarged abdomen. For severe cases of MPS II, a diagnosis is often made between the ages of 18 and 36 months. In milder cases, patients present similarly to children with
404:. Like many components of the body, proteoglycans need to be broken down and replaced. When the body breaks down proteoglycans, one of the resulting products is mucopolysaccharides (GAGs).
484:
Because of the wide variety of phenotypes, the treatment for this disorder is specifically determined for each patient. Until recently, no effective therapy for MPS II was available, so
602:
In 2017, a 44-year-old patient with MPS II was treated with gene therapy in an attempt to prevent further damage by the disease. This is the first case of gene editing being used
1050:
1226:"Study of Intrathecal Idursulfase-IT Administered in Conjunction With Elaprase® in Pediatric Patients With Hunter Syndrome and Early Cognitive Impairment (AIM-IT)"
282:
develops, a further decrease in hand function can occur. The bones themselves may be affected, resulting in short stature. In addition, pebbly, ivory-colored skin
278:
results in decreased ability to pick up small objects. The effects on other joints, such as hips and knees, can make walking normally increasingly difficult. If
703:
969:
1306:
1924:
620:, West Sussex, England, suffocated his 10-year-old son Jacob with a pillow, because of the boy's disabilities related to MPS II. A military
1577:
1555:
740:"Mucopolysaccharidosis type II (Hunter syndrome): a clinical review and recommendations for treatment in the era of enzyme replacement therapy"
699:
1980:
1844:
1880:
1691:
503:
as an enzyme replacement treatment for MPS II. Idursulfase beta, another enzyme replacement treatment, was approved in Korea by the
2299:
499:, a purified form of the missing lysosomal enzyme, underwent clinical trial in 2006 and was subsequently approved by the United States
2314:
1740:
1594:
1128:
303:
2035:
527:
2187:
2069:
1275:
2106:
1849:
1825:
796:
885:"A phase II/III clinical study of enzyme replacement therapy with idursulfase in mucopolysaccharidosis II (Hunter syndrome)"
488:
was used. Recent advances, though, have led to medications that can improve survival and well-being in people with MPS II.
2182:
1760:
431:
even if the child actually has an MPS disorder. A definitive diagnosis of MPS II is made by measuring I2S activity in
2025:
1570:
1448:
218:
The symptoms of Hunter syndrome (MPS II) are generally not apparent at birth. Often, the first symptoms may include
1815:
2059:
1885:
1030:
1021:"Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II"
2101:
2030:
1965:
1684:
1389:
504:
1811:
2192:
1585:
2134:
1714:
1563:
286:
may be found on the upper arms, legs, and upper back of some people with it. These skin lesions are considered
1995:
2216:
1730:
311:
388:
The biochemistry of Hunter syndrome is related to a problem in a part of the connective tissue known as the
1735:
1613:
649:
500:
195:
107:
20:
385:. The failure of this process is the underlying problem in Hunter syndrome and related storage disorders.
2272:
2197:
2091:
1745:
1677:
1648:
1590:
578:
A study in the United
Kingdom indicated an incidence among males around one in 130,000 male live births.
315:
123:
In severe cases, death usually occurs by age 15. In attenuated cases, patients may survive into their 50s
1543:
2267:
1854:
1622:
547:
511:
251:
243:
334:
Since Hunter syndrome is an X-linked recessive disorder, it preferentially affects male patients. The
2227:
2087:
1970:
1750:
1586:
586:
The syndrome is named after physician
Charles A. Hunter (1873–1955), who first described it in 1917.
160:
62:
2262:
1929:
1658:
1459:
1347:
1330:
210:. It has traditionally been categorized as either "mild" or "severe" depending on the presence of
2309:
2232:
2156:
1946:
1875:
515:
295:
81:
38:
2247:
2096:
2054:
2004:
1956:
1898:
834:
Schwartz, Ida VD (2007). "A clinical study of 77 patients with mucopolysaccharidosis type II".
279:
211:
102:
1499:
2079:
1911:
1598:
930:
575:
An estimated 2,000 people have MPS II worldwide, 500 of whom live in the United States.
168:
142:
111:
95:
369:
Dermatan sulfate is one of the GAGs that build up in the tissues of people with MPS II.
1867:
1793:
1765:
926:"Bone marrow transplantation in children with Hunter syndrome: outcome after 7 to 17 years"
555:
543:
539:
389:
1364:
1199:
992:
554:– in a patient with MPS II. Clinical trials by Sangamo involving gene editing using
381:
reactions to support critical functions. One of these functions is the breakdown of large
8:
2064:
1775:
1638:
1437:
655:
1173:
2304:
2237:
1937:
1835:
1150:
1123:
1087:
1025:
901:
884:
859:
764:
739:
672:
263:
188:
156:
71:
1442:
1252:
427:
for GAGs. Abnormal values indicate that an MPS disorder is likely. The urine test can
2129:
1820:
1803:
1470:
1155:
1079:
973:
949:
906:
851:
847:
792:
769:
76:
Skeletal abnormalities, hearing loss, retinal degeneration, enlarged liver and spleen
51:
1283:
863:
2242:
2116:
1643:
1510:
1145:
1137:
1091:
1071:
939:
896:
843:
759:
751:
667:
661:
465:
436:
408:
287:
219:
180:
152:
1225:
1020:
2177:
2124:
2000:
1722:
1626:
1618:
1464:
645:
485:
469:
468:
tissue. If a specific mutation is known to run in the family, prenatal molecular
412:
350:
271:
176:
944:
925:
567:
have minimal neurologic involvement, they may survive into their 50s or beyond.
2257:
2172:
2045:
2010:
1942:
1521:
1141:
1110:
1105:
473:
461:
428:
354:
1532:
1475:
1427:
1395:
1244:
755:
2293:
2252:
2015:
1975:
1903:
1890:
1788:
1783:
1755:
223:
56:
250:
function. The walls of the airway may become thickened, as well, leading to
1862:
1653:
1352:
1159:
977:
953:
910:
855:
773:
632:
401:
382:
239:
159:(or GAGs or mucopolysaccharides) build up in body tissues. It is a form of
1083:
349:
gene which can compensate for the mutant allele. This is known as being a
1700:
1527:
1494:
820:
595:
496:
432:
378:
227:
1410:
460:
diagnosis is routinely available by measuring I2S enzymatic activity in
1516:
1075:
627:, Wragg also claimed that he was under stress after returning from the
440:
424:
374:
1669:
1505:
326:
246:, and a diagnosis is usually made between the ages of 4 and 8 years.
207:
118:
881:
274:
and limited motion. Progressive involvement of the finger and thumb
1538:
1350:, "Former SAS soldier who smothered terminally ill son walks free"
1335:
786:
628:
621:
617:
457:
397:
365:
231:
184:
183:
to accumulate in all body tissues. Hunter syndrome is the only MPS
164:
19:"MPS II" redirects here. For the Chinese romanization system, see
997:
604:
283:
1453:
407:
In MPS II, the problem concerns the breakdown of two GAGs:
1422:
1384:
624:
444:
393:
342:
307:
275:
267:
259:
235:
172:
1062:
Young ID, Harper PS (1982). "Incidence of Hunter's syndrome".
993:"Tests suggest scientists achieved 1st 'in body' gene editing"
2148:
1307:"Early results boost hopes for historic gene editing attempt"
423:
The first laboratory screening test for an MPS disorder is a
291:
255:
521:
345:
for MPS II, she will usually have a normal copy of the
2144:
1985:
787:
James, William D.; Berger, Timothy G.; et al. (2006).
608:
in humans. The study was extended to six patients in 2018.
451:
194:
The symptoms of Hunter syndrome are comparable to those of
594:
Beginning in 2010, a phase I/II clinical trial evaluated
551:
1396:
1276:"Scientists Attempt First Gene Editing Inside a Patient"
330:
MPS II has an X-linked recessive pattern of inheritance.
738:
Wraith JE, Scarpa M, Beck M, et al. (March 2008).
704:
National
Institute of Neurological Disorders and Stroke
1206:. U.S. National Institutes of Health. 31 October 2013
290:
for the disease. Finally, the storage of GAGs in the
1400:
476:
can reveal if someone is a carrier for the disease.
1250:
789:
631:. He denied murdering Jacob, but pleaded guilty to
206:Hunter syndrome may present with a wide variety of
163:. Hunter syndrome is caused by a deficiency of the
1180:. U.S. National Institutes of Health. 15 June 2009
815:Le, Tao; Bhushan, Vikas; Hofmann, Jeffrey (2012).
538:In February 2019, medical scientists working with
447:. In some people with MPS II, analysis of the
234:, a nose with a flattened bridge, and an enlarged
2291:
1253:"US scientists try 1st gene editing in the body"
814:
737:
294:can lead to delayed development with subsequent
1891:Danon disease/glycogen storage disease Type IIb
1232:. U.S. National Institutes of Health. July 2014
262:grow larger with time, the abdomen may become
1996:Color blindness (red and green, but not blue)
1981:Alpha-thalassemia mental retardation syndrome
1685:
1571:
491:
1881:Glucose-6-phosphate dehydrogenase deficiency
1129:Proceedings of the Royal Society of Medicine
546:, California, announced the first "in body"
341:If a female inherits one copy of the mutant
266:, making hernias more noticeable. All major
86:Upper airway disease; cardiovascular failure
1061:
270:may be affected by MPS II, leading to
1692:
1678:
1578:
1564:
984:
61:
37:
1741:X-linked severe combined immunodeficiency
1304:
1274:Marchione, Marilynne (14 November 2017).
1273:
1149:
1136:(Sect Study Dis Child). London: 104–116.
1012:
990:
943:
900:
877:
875:
873:
763:
522:Bone marrow and stem cell transplantation
1251:Marchione, Marilynn (15 November 2017).
966:
833:
733:
731:
729:
727:
725:
723:
721:
364:
325:
304:attention deficit hyperactivity disorder
2135:X-linked nephrogenic diabetes insipidus
2060:Hypohidrotic ectodermal dysplasia (EDA)
1305:Marchione, Mailynn (5 September 2018).
960:
827:
694:
692:
690:
688:
533:
528:hematopoietic stem cell transplantation
2292:
2070:X-linked endothelial corneal dystrophy
1713:
1699:
1367:, "Review 'will clarify murder laws'"
1121:
991:Marchione, Marilyn (7 February 2019).
923:
870:
780:
616:On 24 July 2004, Andrew Wragg, 38, of
155:in which large sugar molecules called
2215:
2214:
2026:Charcot–Marie–Tooth disease (CMTX2-3)
1850:Ornithine transcarbamylase deficiency
1826:X-linked adrenal hypoplasia congenita
1712:
1673:
1559:
1333:, "Father cleared of murdering son",
1106:Hunter's syndrome (Charles A. Hunter)
1018:
917:
718:
201:
1761:X-linked lymphoproliferative disease
1731:Chronic granulomatous disease (CYBB)
810:
808:
685:
16:X-linked recessive genetic condition
2107:Emery–Dreifuss muscular dystrophy 1
392:, which is made up of a variety of
131:1 in 100,000 to 150,000 male births
13:
1816:Spinal and bulbar muscular atrophy
902:10.1097/01.gim.0000232477.37660.fb
791:. Saunders Elsevier. p. 544.
700:"Mucopolysaccharidoses Fact Sheet"
360:
298:and progressive loss of function.
14:
2326:
2300:Proteoglycan metabolism disorders
1886:Pyruvate dehydrogenase deficiency
1377:
1031:U.S. National Library of Medicine
805:
558:are ongoing as of February 2019.
454:can determine clinical severity.
2315:Diseases named after discoverers
1966:X-linked intellectual disability
1659:MPS IX: Hyaluronidase deficiency
1383:
1124:"A Rare Disease in Two Brothers"
848:10.1111/j.1651-2227.2007.00212.x
526:Bone marrow transplantation and
505:Ministry of Food and Drug Safety
1812:Androgen insensitivity syndrome
1649:MPS VI: Maroteaux-Lamy syndrome
1358:
1341:
1324:
1298:
1267:
1218:
1192:
1166:
1115:
1098:
1055:
1044:
570:
2188:Simpson–Golabi–Behmel syndrome
817:First Aid for the USMLE Step 1
1:
2157:AMELX Amelogenesis imperfecta
2097:Centronuclear myopathy (MTM1)
1794:X-linked sideroblastic anemia
1533:Mucopolysaccharidosis Type II
678:
357:, which is a random process.
312:obsessive compulsive disorder
2183:Smith–Fineman–Myers syndrome
2031:Pelizaeus–Merzbacher disease
1925:Purine–pyrimidine metabolism
1639:MPS III: Sanfilippo syndrome
561:
501:Food and Drug Administration
479:
418:
108:Mucopolysaccharidosis type I
46:Patient with Hunter syndrome
21:Mandarin Phonetic Symbols II
7:
2273:Craniofrontonasal dysplasia
2198:Nasodigitoacoustic syndrome
1746:X-linked agammaglobulinemia
945:10.1016/j.jpeds.2008.11.041
639:
589:
377:depends on a vast array of
321:
316:sensory processing disorder
10:
2331:
2268:Orofaciodigital syndrome 1
2102:Conradi–Hünermann syndrome
1855:Oculocerebrorenal syndrome
1587:Lysosomal storage diseases
1142:10.1177/003591571701001833
1051:LaTercera.com (in Spanish)
611:
581:
548:human gene editing therapy
512:enzyme replacement therapy
492:Enzyme replacement therapy
252:obstructive airway disease
18:
2228:X-linked hypophosphatemia
2223:
2210:
2165:
2143:
2115:
2088:Becker muscular dystrophy
2078:
2044:
1955:
1834:
1802:
1774:
1751:Hyper-IgM syndrome type 1
1721:
1708:
1606:
1485:
1404:
1019:Staff (2 February 2019).
756:10.1007/s00431-007-0635-4
161:lysosomal storage disease
127:
117:
101:
90:
80:
70:
50:
45:
36:
31:
2193:Mohr–Tranebjærg syndrome
1736:Wiskott–Aldrich syndrome
1644:MPS IV: Morquio syndrome
171:(I2S). The lack of this
2233:Focal dermal hypoplasia
1947:Occipital horn syndrome
1876:Carbohydrate metabolism
1634:MPS II: Hunter syndrome
1595:carbohydrate metabolism
296:intellectual disability
238:. They may also have a
94:Defiency of the enzyme
2248:Incontinentia pigmenti
2055:Dyskeratosis congenita
1899:Lipid storage disorder
1821:KAL1 Kallmann syndrome
1623:Hurler–Scheie syndrome
1122:Hunter, C. A. (1917).
924:Guffon, N (May 2009).
429:occasionally be normal
370:
331:
280:carpal tunnel syndrome
244:Hurler–Scheie syndrome
212:central nervous system
103:Differential diagnosis
1971:Coffin–Lowry syndrome
1912:Mucopolysaccharidosis
1654:MPS VII: Sly syndrome
1599:Mucopolysaccharidoses
931:Journal of Pediatrics
550:to permanently alter
368:
329:
169:iduronate-2-sulfatase
143:mucopolysaccharidosis
112:mucopolysaccharidoses
96:iduronate-2-sulfatase
2263:Lujan–Fryns syndrome
1930:Lesch–Nyhan syndrome
1868:Adrenoleukodystrophy
1766:Properdin deficiency
1392:at Wikimedia Commons
972:. pp. 487–496.
889:Genetics in Medicine
556:zinc finger nuclease
540:Sangamo Therapeutics
534:Gene editing therapy
390:extracellular matrix
2065:X-linked ichthyosis
1286:on 15 November 2017
656:Sanfilippo syndrome
542:, headquartered in
516:blood–brain barrier
510:Recent advances in
226:, runny noses, and
2238:Fragile X syndrome
2048:and related tissue
1715:X-linked recessive
1486:External resources
1255:. Associated Press
1230:Clinicaltrials.gov
1204:Clinicaltrials.gov
1178:Clinicaltrials.gov
1076:10.1007/BF00569230
1026:ClinicalTrials.gov
970:Minerva Pediatrica
706:. 15 November 2017
673:Genetic counseling
472:can be performed.
371:
332:
202:Signs and symptoms
189:X-linked recessive
157:glycosaminoglycans
2285:
2284:
2281:
2280:
2217:X-linked dominant
2206:
2205:
2166:No primary system
1667:
1666:
1553:
1552:
1388:Media related to
798:978-0-7216-2921-6
437:white blood cells
220:abdominal hernias
135:
134:
26:Medical condition
2322:
2243:Aicardi syndrome
2212:
2211:
1710:
1709:
1694:
1687:
1680:
1671:
1670:
1580:
1573:
1566:
1557:
1556:
1402:
1401:
1387:
1371:
1362:
1356:
1345:
1339:
1328:
1322:
1321:
1319:
1317:
1302:
1296:
1295:
1293:
1291:
1282:. Archived from
1271:
1265:
1264:
1262:
1260:
1248:
1242:
1241:
1239:
1237:
1222:
1216:
1215:
1213:
1211:
1196:
1190:
1189:
1187:
1185:
1170:
1164:
1163:
1153:
1119:
1113:
1102:
1096:
1095:
1059:
1053:
1048:
1042:
1041:
1039:
1037:
1016:
1010:
1009:
1007:
1005:
988:
982:
981:
964:
958:
957:
947:
921:
915:
914:
904:
879:
868:
867:
836:Acta Paediatrica
831:
825:
824:
812:
803:
802:
784:
778:
777:
767:
735:
716:
715:
713:
711:
696:
668:Prenatal testing
662:Morquio syndrome
466:chorionic villus
409:dermatan sulfate
181:dermatan sulfate
153:genetic disorder
66:
65:
41:
29:
28:
2330:
2329:
2325:
2324:
2323:
2321:
2320:
2319:
2290:
2289:
2286:
2277:
2219:
2202:
2178:McLeod syndrome
2161:
2139:
2125:Alport syndrome
2111:
2074:
2040:
2001:Ocular albinism
1951:
1917:Hunter syndrome
1830:
1798:
1770:
1717:
1704:
1698:
1668:
1663:
1627:Scheie syndrome
1619:Hurler syndrome
1602:
1584:
1554:
1549:
1548:
1522:Hunter syndrome
1481:
1480:
1413:
1390:Hunter syndrome
1380:
1375:
1374:
1363:
1359:
1346:
1342:
1329:
1325:
1315:
1313:
1303:
1299:
1289:
1287:
1272:
1268:
1258:
1256:
1249:
1245:
1235:
1233:
1224:
1223:
1219:
1209:
1207:
1198:
1197:
1193:
1183:
1181:
1172:
1171:
1167:
1120:
1116:
1103:
1099:
1060:
1056:
1049:
1045:
1035:
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1017:
1013:
1003:
1001:
989:
985:
965:
961:
922:
918:
880:
871:
832:
828:
813:
806:
799:
785:
781:
744:Eur. J. Pediatr
736:
719:
709:
707:
698:
697:
686:
681:
646:Hurler syndrome
642:
614:
599:began in 2014.
592:
584:
573:
564:
536:
524:
494:
486:palliative care
482:
470:genetic testing
421:
413:heparan sulfate
363:
361:Pathophysiology
351:genetic carrier
324:
272:joint stiffness
204:
177:heparan sulfate
138:Hunter syndrome
60:
32:Hunter syndrome
27:
24:
17:
12:
11:
5:
2328:
2318:
2317:
2312:
2310:Rare syndromes
2307:
2302:
2283:
2282:
2279:
2278:
2276:
2275:
2270:
2265:
2260:
2258:CHILD syndrome
2255:
2250:
2245:
2240:
2235:
2230:
2224:
2221:
2220:
2208:
2207:
2204:
2203:
2201:
2200:
2195:
2190:
2185:
2180:
2175:
2173:Barth syndrome
2169:
2167:
2163:
2162:
2160:
2159:
2153:
2151:
2141:
2140:
2138:
2137:
2132:
2130:Dent's disease
2127:
2121:
2119:
2113:
2112:
2110:
2109:
2104:
2099:
2094:
2084:
2082:
2076:
2075:
2073:
2072:
2067:
2062:
2057:
2051:
2049:
2042:
2041:
2039:
2038:
2033:
2028:
2019:
2018:
2013:
2011:Norrie disease
2008:
1998:
1993:Eye disorders:
1989:
1988:
1983:
1978:
1973:
1961:
1959:
1957:Nervous system
1953:
1952:
1950:
1949:
1943:Menkes disease
1933:
1932:
1920:
1919:
1907:
1906:
1894:
1893:
1888:
1883:
1871:
1870:
1858:
1857:
1852:
1840:
1838:
1832:
1831:
1829:
1828:
1823:
1818:
1808:
1806:
1800:
1799:
1797:
1796:
1791:
1786:
1780:
1778:
1772:
1771:
1769:
1768:
1763:
1758:
1753:
1748:
1743:
1738:
1733:
1727:
1725:
1719:
1718:
1706:
1705:
1697:
1696:
1689:
1682:
1674:
1665:
1664:
1662:
1661:
1656:
1651:
1646:
1641:
1636:
1631:
1630:
1629:
1610:
1608:
1604:
1603:
1583:
1582:
1575:
1568:
1560:
1551:
1550:
1547:
1546:
1535:
1524:
1513:
1502:
1490:
1489:
1487:
1483:
1482:
1479:
1478:
1467:
1456:
1445:
1430:
1414:
1409:
1408:
1406:
1405:Classification
1399:
1398:
1393:
1379:
1378:External links
1376:
1373:
1372:
1365:NEWS.BBC.co.uk
1357:
1348:Guardian.co.uk
1340:
1331:NEWS.BBC.co.uk
1323:
1297:
1266:
1243:
1217:
1191:
1165:
1114:
1097:
1054:
1043:
1011:
983:
959:
938:(5): 733–737.
916:
869:
842:(455): 63–70.
826:
823:. p. 117.
804:
797:
779:
717:
683:
682:
680:
677:
676:
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665:
659:
653:
641:
638:
613:
610:
591:
588:
583:
580:
572:
569:
563:
560:
535:
532:
523:
520:
493:
490:
481:
478:
474:DNA sequencing
462:amniotic fluid
420:
417:
362:
359:
355:X-inactivation
323:
320:
224:ear infections
203:
200:
133:
132:
129:
125:
124:
121:
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114:
105:
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2295:
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2259:
2256:
2254:
2253:Rett syndrome
2251:
2249:
2246:
2244:
2241:
2239:
2236:
2234:
2231:
2229:
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2222:
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2105:
2103:
2100:
2098:
2095:
2093:
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2085:
2083:
2081:
2080:Neuromuscular
2077:
2071:
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2058:
2056:
2053:
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2047:
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2029:
2027:
2024:
2021:
2020:
2017:
2016:Choroideremia
2014:
2012:
2009:
2006:
2002:
1999:
1997:
1994:
1991:
1990:
1987:
1984:
1982:
1979:
1977:
1976:MASA syndrome
1974:
1972:
1969:
1967:
1963:
1962:
1960:
1958:
1954:
1948:
1944:
1941:
1939:
1935:
1934:
1931:
1928:
1926:
1922:
1921:
1918:
1915:
1913:
1909:
1908:
1905:
1904:Fabry disease
1901:
1900:
1896:
1895:
1892:
1889:
1887:
1884:
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1879:
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1873:
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1819:
1817:
1813:
1810:
1809:
1807:
1805:
1801:
1795:
1792:
1790:
1789:Haemophilia B
1787:
1785:
1784:Haemophilia A
1782:
1781:
1779:
1777:
1773:
1767:
1764:
1762:
1759:
1757:
1754:
1752:
1749:
1747:
1744:
1742:
1739:
1737:
1734:
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1620:
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1611:
1609:
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1600:
1596:
1592:
1591:Inborn errors
1588:
1581:
1576:
1574:
1569:
1567:
1562:
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1558:
1545:
1541:
1540:
1536:
1534:
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1523:
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1518:
1514:
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1508:
1507:
1503:
1501:
1497:
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1403:
1397:
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1355:
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1349:
1344:
1338:
1337:
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1327:
1312:
1308:
1301:
1285:
1281:
1277:
1270:
1254:
1247:
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1227:
1221:
1205:
1201:
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1179:
1175:
1169:
1161:
1157:
1152:
1147:
1143:
1139:
1135:
1131:
1130:
1125:
1118:
1112:
1111:Who Named It?
1108:
1107:
1101:
1093:
1089:
1085:
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1073:
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1058:
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979:
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955:
951:
946:
941:
937:
933:
932:
927:
920:
912:
908:
903:
898:
895:(8): 465–73.
894:
890:
886:
878:
876:
874:
865:
861:
857:
853:
849:
845:
841:
837:
830:
822:
818:
811:
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800:
794:
790:
783:
775:
771:
766:
761:
757:
753:
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749:
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741:
734:
732:
730:
728:
726:
724:
722:
705:
701:
695:
693:
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367:
358:
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352:
348:
344:
339:
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328:
319:
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313:
309:
305:
299:
297:
293:
289:
288:pathognomonic
285:
281:
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257:
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241:
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229:
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197:
192:
191:inheritance.
190:
186:
182:
178:
174:
170:
166:
162:
158:
154:
151:), is a rare
150:
146:
144:
139:
130:
126:
122:
120:
116:
113:
109:
106:
104:
100:
97:
93:
89:
85:
83:
82:Complications
79:
75:
73:
69:
64:
58:
57:Endocrinology
55:
53:
49:
44:
40:
35:
30:
22:
2287:
2022:
1992:
1964:
1936:
1923:
1916:
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1897:
1874:
1863:Dyslipidemia
1861:
1843:
1633:
1537:
1526:
1515:
1504:
1493:
1469:
1458:
1447:
1432:
1417:
1368:
1360:
1353:The Guardian
1351:
1343:
1334:
1326:
1314:. Retrieved
1310:
1300:
1288:. Retrieved
1284:the original
1279:
1269:
1257:. Retrieved
1246:
1234:. Retrieved
1229:
1220:
1208:. Retrieved
1203:
1194:
1182:. Retrieved
1177:
1168:
1133:
1127:
1117:
1104:
1100:
1070:(4): 391–2.
1067:
1063:
1057:
1046:
1034:. Retrieved
1024:
1014:
1002:. Retrieved
996:
986:
962:
935:
929:
919:
892:
888:
839:
835:
829:
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788:
782:
747:
743:
708:. Retrieved
633:manslaughter
615:
603:
601:
593:
585:
577:
574:
571:Epidemiology
565:
537:
525:
509:
495:
483:
456:
448:
422:
406:
402:proteoglycan
387:
383:biomolecules
372:
346:
340:
335:
333:
300:
248:
217:
205:
193:
148:
141:
137:
136:
1776:Hematologic
1528:GeneReviews
1495:MedlinePlus
1316:6 September
1290:15 November
1259:16 November
821:McGraw-Hill
596:intrathecal
497:Idursulfase
441:fibroblasts
379:biochemical
187:to exhibit
2294:Categories
1845:Amino acid
1607:Catabolism
1517:Patient UK
1471:DiseasesDB
1064:Hum. Genet
1036:7 February
1004:7 February
679:References
625:specialist
443:from skin
425:urine test
375:human body
240:large head
208:phenotypes
2305:Syndromes
1836:Metabolic
1804:Endocrine
1703:disorders
1506:eMedicine
658:(MPS III)
562:Prognosis
480:Treatment
419:Diagnosis
314:, and/or
264:distended
254:. As the
165:lysosomal
128:Frequency
119:Prognosis
52:Specialty
2117:Urologic
2092:Duchenne
1701:X-linked
1539:Orphanet
1511:ped/1029
1369:BBC News
1336:BBC News
1160:19979883
978:24056375
954:19167723
911:16912578
864:23119106
856:17391446
774:18038146
664:(MPS IV)
640:See also
629:Iraq War
622:security
618:Worthing
590:Research
544:Richmond
458:Prenatal
398:proteins
322:Genetics
232:forehead
185:syndrome
110:; other
72:Symptoms
1938:Mineral
1465:D016532
1311:AP News
1236:20 July
1210:20 July
1184:22 July
1151:2018097
1092:9667145
1084:6809596
998:AP News
765:2234442
612:Society
605:in vivo
582:History
284:lesions
175:causes
167:enzyme
145:type II
2023:Other:
1723:Immune
1500:001203
1454:309900
1158:
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909:
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854:
795:
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710:11 May
464:or in
445:biopsy
394:sugars
343:allele
308:autism
276:joints
268:joints
260:spleen
236:tongue
173:enzyme
149:MPS II
91:Causes
59:
2149:tooth
2036:SMAX2
1614:MPS I
1443:277.5
1428:E76.1
1088:S2CID
860:S2CID
650:MPS I
439:, or
433:serum
292:brain
256:liver
228:colds
196:MPS I
140:, or
2145:Bone
2046:Skin
1986:PHF8
1756:IPEX
1476:6050
1460:MeSH
1449:OMIM
1438:9-CM
1318:2018
1292:2017
1280:Time
1261:2017
1238:2014
1212:2014
1186:2018
1156:PMID
1080:PMID
1038:2019
1006:2019
974:PMID
950:PMID
907:PMID
852:PMID
793:ISBN
770:PMID
712:2018
452:gene
411:and
396:and
373:The
258:and
179:and
1593:of
1544:580
1434:ICD
1419:ICD
1146:PMC
1138:doi
1109:at
1072:doi
940:doi
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760:PMC
752:doi
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552:DNA
449:I2S
347:IDS
336:IDS
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