428:
material from an infantile case with amaurotic idiocy. The glycolipid analysis soon demonstrated differences from all the cases studied before. Besides the neuronal storage of GM2, the storage of GA2 was much more pronounced, and different from all cases of Tay-Sachs disease studied so far, globoside accumulated in the visceral organs and, most importantly, hexosaminidase activity was almost completely absent. The disease causing catabolic enzyme deficiency of hexosaminidases was demonstrated with four different substrates (p–nitrophenyl-β-D-N-acetylglucosaminide, p-nitrophenyl-β-D-N-acetylgalactosaminide, glycolipid GA2 and globoside) in four different organs and published in 1968.
71:
104:. The classic infantile form of the disease has the most severe symptoms and is incredibly hard to diagnose at this early age. The first signs of symptoms begin before 6 months of age and the parents’ notice when the child begins regressing in their development. If the children had the ability to sit up by themselves or crawl they will lose this ability. This is caused by a slow deterioration of the muscles in the child's body from the buildup of GM2
47:
399:
suffer from aspiration or lack the ability to change from the passageway to their lungs versus their stomach and their spit travels to the lungs causing bronchopneumonia. The patient also lacks the ability to cough and therefore must undergo a treatment to shake up their body to remove the mucus from the lining of their lungs. Medication is also given to patients to lessen their symptoms including seizures.
116:, it is unable to attach to these gangliosides to break them apart and make them non-toxic. With this buildup there are several symptoms that begin to appear such as muscle/motor weakness, sharp reaction to loud noises, blindness, deafness, inability to react to stimulants, respiratory problems and infections, mental retardation, seizures, cherry red spots in the retina, enlarged liver and spleen (
416:
424:
analysis of various patients with amaurotic idiocy by Konrad
Sandhoff (born 1939), a German biochemist, led to the identification of several biochemically distinct diseases: the first biochemical description of GM1-gangliosidosis in 1963, Sandhoff disease in 1968, Tay-Sachs-Disease, the AB-variant of GM2-Gangliosidosis and the B1-variant of GM2-gangliosidosis.
427:
The molecular defect in
Sandhoff disease was discovered when Sandhoff studied the biochemistry of sphingolipids and gangliosides in the laboratory of Prof. Horst Jatzkewitz (1912–2002), a German biochemist (Max Planck Institute for Psychiatry, Munich). In October 1966, he obtained deep-frozen autopsy
307:
screening if they are at high risk, to determine their carrier status before they have children. However, it is also highly recommended to undergo testing even for those parents who do not have a family history of
Sandhoff disease. Over 95% of the families that have children with Sandhoff disease had
229:
rather than a high population frequency, because
Ashkenazi Jews were the targeted population in a mass screening program for Tay-Sachs disease. Several rare SD mutations were discovered as researchers resolved cases of enzyme deficiency among suspected TSD carriers, but no cases of the disease itself
398:
to manage seizures or medications to treat respiratory infections, and consume a precise diet consisting of puree foods due to difficulties swallowing. Infants with the disease usually die by the age of 3 due to respiratory infections. The patient must be under constant surveillance because they can
233:
However, since it is an autosomal recessive disease, it is likely found in any ethnic group passing from generation to generation through carriers without being expressed in their offspring. Even though the family may not have a history of
Sandhoff disease, it is possible for two individuals to have
171:
particularly within the C1214T allele caused the adult onset form of
Sandhoff Disease. For the patient showing symptoms of the infantile or juvenile form they have a mutation on exon I207V from their father, and a 16 base pair deletion from their mother which can be located on as many as five exons,
406:
in mice, as well as stem cell treatment in humans and other medical treatments recruiting test patients. A Sandhoff disease study showing proof of principle for gene therapy in a human model system using CRISPR and virus gene correction gives the chance for clinical trials to cure the disease. The
423:
Sandhoff disease is one of several forms of what was formerly known as amaurotic idiocy. This inherited disease is characterized by the accumulation of lipid-containing cells in the viscera and in the nervous system, mental retardation, and impaired vision or blindness. The chemical and enzymatic
302:
to determine if the above-noted compounds are abnormally stored within the body. For a child to suffer from this disease, both parents must be carriers, and both must transmit the mutation to the child. Thus, even in the case where both parents have the mutation, there is only a 25 percent chance
131:
The other two forms of
Sandhoff disease have similar symptoms but to a lesser extent. Adult and juvenile forms of Sandhoff disease are more rare than the infantile form. In these cases victims suffer cognitive impairment (retardation) and a loss of muscle coordination that impairs and eventually
87:
caused by the inherited deficiency to create functional beta-hexosaminidases A and B. These catabolic enzymes are needed to degrade the neuronal membrane components, ganglioside GM2, its derivative GA2, the glycolipid globoside in visceral tissues, and some oligosaccharides. Accumulation of these
312:
gene does not cause clinical symptoms when only one copy is present, and often passed undetected from one generation to the next
Naturally, if an individual carries the mutation, he or she has a risk of transmitting it to the unborn child. Genetic counseling is recommended for those who have the
335:
Classic infantile form of the disease is classified by the development of symptoms anywhere from 2 months to 9 months of age. It is the most common and most severe of all of the forms and will lead to death before the patient reaches the age of three. Infants with this disorder typically appear
316:
It is possible for parents who are about to have a child or had a child with
Sandhoff Disease can have a PGD or PEGD. PEGD is pre-embryonic genetic diagnosis for the parents that would not benefit from a pre-implantation genetic diagnosis because of their religion or negative attitude for the
380:
Juvenile and adult onset forms of
Sandhoff disease are very rare. Signs and symptoms can begin in childhood, adolescence, or adulthood and are usually milder than those seen with the infantile form of Sandhoff disease. As in the infantile form, mental abilities and coordination are affected.
393:
Currently Sandhoff disease does not have any standard treatment and does not have a cure. However, a person suffering from the disease needs proper nutrition, hydration, and maintenance of clear airways. To reduce some symptoms that may occur with Sandhoff disease, the patient may take
375:
Adult onset form of the disease is classified by its occurrence in older individuals and has an effect on the motor function of these individuals. It is not yet known if Sandhoff disease will cause these individuals to have a decrease in their life
132:
destroys their ability to walk; the characteristic red spots in the retina also develop. The adult form of the disease, however, is sometimes milder, and may only lead to muscle weakness that impairs walking or the ability to get out of bed.
1538:
1523:
1508:
321:
to be produced by two parents if they were to conceive a child. If the family has a history of Sandhoff disease it is recommended they have their genome sequenced to ensure they are not carriers or to sequence the genome of their child.
367:
The juvenile form of the disease shows symptoms starting at age 3 ranging to age 10 and, although the child usually dies by the time they are 15, it is possible for them to live longer if they are under constant care. Symptoms include
568:
Pilz H, MĂĽller D, Sandhoff K, ter Meulen V (September 1968). "Tay-Sachssche Krankheit mit Hexosaminidase-Defekt (Klinische, morphologische und biochemische Befunde bei einem Fall mit viszeraler Speicherung von Nierenglobosid)".
259:, which function in nerve cells to break down fatty substances, complex sugars, and molecules that are linked to sugars. In particular, beta-hexosaminidase A breaks down a fatty compound called GM2 ganglioside. Mutations in the
155:
in the HEX B gene located within chromosome 5 (see figure bottom), leading to the differences in severities of the symptoms. The difference in the codons has the consequence of inhibiting two enzymes located in the
330:
There are three types of Sandhoff disease: classic infantile, juvenile, and adult late onset. Each form is classified by the severity of the symptoms as well as the age at which the patient shows these symptoms.
979:
Chamoles NA, Blanco M, Gaggioli D, Casentini C (April 2002). "Tay-Sachs and Sandhoff diseases: enzymatic diagnosis in dried blood spots on filter paper: retrospective diagnoses in newborn-screening cards".
878:
Kleiman FE, et al. (1994). "Sandhoff disease in Argentina: high frequency of a splice site mutation in the HEXB gene and correlation between enzyme and DNA-based tests for heterozygote detection".
92:, another genetic disorder that disrupts beta-hexosaminidases A and S. There are three subsets of Sandhoff disease based on when first symptoms appear: classic infantile, juvenile and adult late onset.
88:
metabolites leads to a progressive destruction of the central nervous system and eventually to death. The rare autosomal recessive neurodegenerative disorder is clinically almost indistinguishable from
471:
Sandhoff K, Andreae U, Jatzkewitz H (March 1968). "Deficient hexosaminidase activity in an exceptional case of Tay-Sachs disease with additional storage of kidney globoside in visceral organs".
957:
Cantor RM, Kaback MM (1985). "Sandhoff disease (SHD) heterozygote frequencies (HF) in North American (NA) Jewish (J) and non-Jewish (NJ) populations: implications for carrier (C) screening".
185:
Articles regarding Sandhoff disease frequencies among distinct groups of people contain discrepancies from one another. More than 25 mutations have been reported other than novel mutations.
266:
As a result, progressive damage caused by the resulting buildup of GM2 ganglioside leads to the destruction of nerve cells, causing the signs and symptoms associated with Sandhoff disease.
1186:
Allende, Maria L.; Cook, Emily K.; Larman, Bridget C.; Nugent, Adrienne; Brady, Jacqueline M.; Golebiowski, Diane; Sena-Esteves, Miguel; Tifft, Cynthia J.; Proia, Richard L. (2018-01-22).
1485:
922:
Drousiotou A, et al. (2000). "Sandhoff disease in Cyprus: population screening by biochemical and DNA analysis indicates a high frequency of carriers in the Maronite community".
1362:"AB variant of infantile GM2 gangliosidosis: deficiency of a factor necessary for stimulation of hexosaminidase A-catalyzed degradation of ganglioside GM2 and glycolipid GA2"
1050:
Zhang, Zhi-Xin; Nobuaki Wakamatsu; Emilie H. Mulesi; George H. Thomasi; Roy A. Gravel (1994). "Impact of premature stop codons on mRNA levels in infantile Sandhoff disease".
612:
Harzer K, Sandhoff K, Schall H, Kollmann F (November 1971). "Enzymatische Untersuchungen im Blut von Überträgern einer Variante der Tay-Sachsschen Erkrankung (Variante 0)".
1638:
682:
Gomez-Lira M, Sangalli A, Mottes M, Perusi C, Pignatti PF, Rizzuto N, Salviati A (1995). "A common β hexosaminidase gene mutation in adult Sandhoff disease patients".
385:) and other problems with movement, speech problems, and mental illness. These signs and symptoms vary widely among people with late-onset forms of Sandhoff disease.
1245:
164:
contain various enzymes to break down byproducts and toxins to ensure they do not accumulate enough to interfere with the function of the central nervous system.
1775:
234:
a child with the disease. Since Sandhoff disease was only discovered in 1968, there are years the disease has gone undetected because of misdiagnoses.
1969:
1110:
Hendriksz CJ, Corry PC, Wraith JE, Besley GT, Cooper A, Ferrie CD (2004). "Juvenile Sandhoff disease-Nine New Cases and a review of the literature".
1883:
360:, which can be identified with an eye examination, is characteristic of this disorder. Some infants with Sandhoff disease may have enlarged organs (
140:
Two parents carrying a mutated gene and passing it on to their offspring cause the disease. Even with both parents carrying the disease in their
1949:
175:
1631:
1959:
1616:
832:
1553:
659:
1170:
1914:
1085:
1780:
1954:
1918:
1655:
1624:
1888:
1015:
Kuliev A, Rechitsky S, Laziuk K, Verlinsky O, Tur-Kaspa I, Verlinsky Y (2006). "Pre-Embryonic diagnosis for Sandhoff Disease".
1909:
1875:
1721:
437:
344:
such as turning over, sitting, and crawling. As the disease progresses, infants develop seizures, vision and hearing loss,
144:, there is only a 25% chance that they will have a child containing the genetic coding for the disease (see figure right).
1830:
1309:
Okada S, O'Brien JS (August 1969). "Tay-Sachs disease: generalized absence of a beta-D-N-acetylhexosaminidase component".
274:
Sandhoff disease can be detected through the following procedures (before it is apparent through physical examination): a
1253:
1825:
1188:"Cerebral organoids derived from Sandhoff disease induced pluripotent stem cells exhibit impaired neurodifferentiation"
1651:
1647:
1771:
147:
Each form of the disease is caused by the differences in the various mutations of the genome, in particular the
1564:
403:
364:) or bone abnormalities. Children with the severe form of this disorder usually live only into early childhood.
202:
1246:"Sandhoff disease study shows proof of principle for gene therapy - Scienmag: Latest Science and Health News"
263:
gene disrupt the activity of these enzymes, preventing the breakdown of GM2 ganglioside and other molecules.
1964:
1928:
1659:
1480:
113:
84:
1716:
101:
89:
1741:
1604:
1274:
Jatzkewitz H, Sandhoff K (June 1963). "On a biochemically special form of infantile amaturotic idiocy".
256:
252:
1790:
1421:"Variant of GM2-gangliosidosis with hexosaminidase A having a severely changed substrate specificity"
1373:
1318:
524:
1542:
251:
cause Sandhoff disease. The gene provides instructions for making a protein crucial to the enzymes
188:
One article says that Sandhoff disease is found commonly in individuals with a non-Jewish descent.
70:
1153:
Karbani, Gulshan A (15 May 2012). "Genetic Counselling: Consanguinity and Cultural Expectations".
1835:
1707:
1702:
1342:
1135:
904:
707:
637:
594:
550:
291:
226:
117:
303:
their child will inherit the condition. Frequently, parents are given the opportunity to have a
1575:
1450:
1401:
1334:
1291:
1227:
1209:
1166:
1127:
1067:
1032:
997:
939:
896:
836:
811:
699:
629:
586:
542:
488:
59:
728:
1786:
1668:
1440:
1432:
1391:
1381:
1326:
1283:
1217:
1199:
1158:
1119:
1059:
1024:
989:
931:
888:
801:
691:
621:
578:
532:
480:
125:
1532:
395:
357:
283:
46:
1123:
1089:
1377:
1322:
1162:
528:
1922:
1893:
1861:
1839:
1811:
1689:
1436:
1222:
1187:
806:
789:
287:
222:
1547:
1445:
1420:
1396:
1361:
1028:
993:
1943:
1764:
1756:
1745:
1287:
598:
537:
512:
484:
64:
1139:
711:
554:
1806:
1346:
908:
749:
641:
361:
341:
295:
206:
168:
105:
174:
1569:
1330:
1849:
1698:
1684:
1580:
415:
1517:
381:
Characteristic features include muscle weakness, loss of muscle coordination (
299:
1213:
1821:
1801:
1733:
1527:
442:
353:
349:
196:
161:
121:
1386:
1295:
1231:
1131:
1036:
1001:
943:
582:
546:
1454:
1338:
1071:
1063:
935:
900:
703:
633:
590:
492:
1857:
1673:
1599:
815:
345:
211:
157:
1405:
1204:
407:
ultra-rare occurrence is a main hurdle to overcome for clinical trials.
892:
695:
625:
513:"Variation of beta-N-acetylhexosaminidase-pattern in Tay-Sachs disease"
308:
no known prior family history of the condition, as the mutation in the
109:
1500:
372:, ataxia, motor skills regression, spacticity, and learning disorders.
1512:
382:
369:
337:
318:
275:
215:
148:
141:
336:
normal until the age of 3 to 6 months, when development slows and
279:
152:
402:
Currently the government is testing several treatments including
1558:
663:
248:
244:
167:
Using restriction enzymes, it was discovered that a mutation on
54:
Sandhoff disease is inherited via an autosomal recessive manner.
1620:
304:
1419:
Kytzia HJ, Hinrichs U, Maire I, Suzuki K, Sandhoff K (1983).
100:
Sandhoff disease symptoms are clinically indeterminable from
835:. Department of Neurology Jefferson Hospital. Archived from
860:. National Tay-Sachs & Allied Disease Association, Inc
1467:
317:
discarding of embryos. PEGD sequences the genome of the
857:
1466:
This article incorporates some public domain text from
1086:"From a parents perspective: Parents view of Sandhoff"
1490:
290:
and tissues (to determine the presence of a genetic
1902:
1874:
1847:
1799:
1754:
1731:
1682:
1667:
1590:
1494:
58:
26:
21:
340:used for movement weaken. Affected infants lose
160:of the neurons of the central nervous system.
1632:
8:
827:
825:
1679:
1639:
1625:
1617:
1491:
1088:. sandhoffdisease.webs.com. Archived from
108:. Since the body is unable to create the
69:
45:
18:
1444:
1395:
1385:
1221:
1203:
805:
783:
781:
774:. Lippincott Williams & Wilkin. 2008.
536:
1360:Conzelmann E, Sandhoff K (August 1978).
1250:Scienmag: Latest Science and Health News
414:
191:Others say that it is more commonly in:
833:"Lysosomal Diseases Testing Laboratory"
790:"Carrier detection in Sandhoff disease"
677:
675:
673:
671:
454:
1112:Journal of Inherited Metabolic Disease
974:
972:
723:
721:
655:
653:
651:
1468:The U.S. National Library of Medicine
506:
504:
502:
278:removing a sample of tissue from the
242:Biallelic pathogenic variants in the
7:
466:
464:
462:
460:
458:
1163:10.1002/9780470015902.a0006179.pub2
660:Online Mendelian Inheritance in Man
1437:10.1002/j.1460-2075.1983.tb01567.x
1124:10.1023/B:BOLI.0000028777.38551.5a
959:American Journal of Human Genetics
794:American Journal of Human Genetics
729:"Introduction to Sandhoff Disease"
221:Discovery of several mutations in
195:the Creole population of northern
14:
1915:Cholesteryl ester storage disease
39:hexosaminidase A and B deficiency
1970:Diseases named after discoverers
1919:Lysosomal acid lipase deficiency
770:"Symptoms of Sandhoff Disease".
173:
1017:Reproductive BioMedicine Online
788:Lowden JA, et al. (1978).
731:. The Medical Biochemistry Page
35:variant 0 of GM2-gangliosidosis
1910:Cerebrotendinous xanthomatosis
438:GM2-gangliosidosis, AB variant
1:
1950:Autosomal recessive disorders
1831:Multiple sulfatase deficiency
1155:Encyclopedia Of Life Sciences
1029:10.1016/S1472-6483(10)61005-X
994:10.1016/S0009-8981(02)00002-5
1826:Metachromatic leukodystrophy
1331:10.1126/science.165.3894.698
1288:10.1016/0006-3002(63)90764-9
1252:. 2018-02-22. Archived from
538:10.1016/0014-5793(69)80274-7
485:10.1016/0024-3205(68)90024-6
1960:Neurodegenerative disorders
1889:Jansky–Bielschowsky disease
31:Sandhoff–Jatzkewitz disease
1986:
1648:Lysosomal storage diseases
511:Sandhoff K (August 1969).
181:Mutations and polymorphism
1192:Journal of Lipid Research
752:. Genetics Home Reference
664:Sandhoff Disease - 268800
53:
44:
1366:Proc Natl Acad Sci U S A
1052:Human Molecular Genetics
404:N-butyl-deoxynojirimycin
286:, molecular analysis of
83:is a lysosomal genetic,
1955:Lipid storage disorders
1660:Lipid storage disorders
1929:Sea-blue histiocytosis
1387:10.1073/pnas.75.8.3979
772:Medical Books Excerpts
583:10.1055/s-0028-1110836
420:
114:central nervous system
85:lipid storage disorder
1742:Globotriaosylceramide
936:10.1007/s004390050003
418:
356:abnormality called a
298:, and occasionally a
257:beta-hexosaminidase B
253:beta-hexosaminidase A
1772:Niemann–Pick disease
1276:Biochim Biophys Acta
982:Clinica Chimica Acta
571:Dtsch Med Wochenschr
230:have been reported.
112:it needs within the
1378:1978PNAS...75.3979C
1323:1969Sci...165..698O
1205:10.1194/jlr.M081323
1064:10.1093/hmg/3.1.139
529:1969FEBSL...4..351S
1836:Galactocerebroside
1708:GM2 gangliosidoses
1703:GM1 gangliosidoses
1591:External resources
893:10.1007/bf00208283
750:"Sandhoff Disease"
696:10.1007/bf00191799
626:10.1007/bf01732464
421:
292:metabolic disorder
227:ascertainment bias
212:Christian Maronite
118:hepatosplenomegaly
96:Symptoms and signs
1937:
1936:
1870:
1869:
1791:Gaucher's disease
1717:Tay–Sachs disease
1614:
1613:
858:"Carrier Testing"
839:on April 10, 2009
214:communities from
102:Tay–Sachs disease
90:Tay–Sachs disease
78:
77:
16:Medical condition
1977:
1787:Glucocerebroside
1776:SMPD1-associated
1712:Sandhoff disease
1680:
1669:Sphingolipidoses
1656:lipid metabolism
1641:
1634:
1627:
1618:
1492:
1481:Sandhoff Disease
1459:
1458:
1448:
1416:
1410:
1409:
1399:
1389:
1357:
1351:
1350:
1317:(894): 698–700.
1306:
1300:
1299:
1271:
1265:
1264:
1262:
1261:
1242:
1236:
1235:
1225:
1207:
1183:
1177:
1176:
1150:
1144:
1143:
1107:
1101:
1100:
1098:
1097:
1082:
1076:
1075:
1047:
1041:
1040:
1012:
1006:
1005:
976:
967:
966:
954:
948:
947:
919:
913:
912:
875:
869:
868:
866:
865:
854:
848:
847:
845:
844:
829:
820:
819:
809:
785:
776:
775:
767:
761:
760:
758:
757:
746:
740:
739:
737:
736:
725:
716:
715:
679:
666:
657:
646:
645:
609:
603:
602:
565:
559:
558:
540:
508:
497:
496:
468:
419:Sphingolipidoses
177:
126:bronchopneumonia
81:Sandhoff disease
74:
73:
49:
22:Sandhoff disease
19:
1985:
1984:
1980:
1979:
1978:
1976:
1975:
1974:
1940:
1939:
1938:
1933:
1898:
1866:
1843:
1804:
1795:
1750:
1746:Fabry's disease
1727:
1687:
1671:
1663:
1645:
1615:
1610:
1609:
1586:
1585:
1503:
1476:
1463:
1462:
1418:
1417:
1413:
1359:
1358:
1354:
1308:
1307:
1303:
1273:
1272:
1268:
1259:
1257:
1244:
1243:
1239:
1185:
1184:
1180:
1173:
1152:
1151:
1147:
1109:
1108:
1104:
1095:
1093:
1084:
1083:
1079:
1049:
1048:
1044:
1014:
1013:
1009:
978:
977:
970:
956:
955:
951:
921:
920:
916:
877:
876:
872:
863:
861:
856:
855:
851:
842:
840:
831:
830:
823:
787:
786:
779:
769:
768:
764:
755:
753:
748:
747:
743:
734:
732:
727:
726:
719:
681:
680:
669:
658:
649:
620:(21): 1189–91.
614:Klin Wochenschr
611:
610:
606:
567:
566:
562:
510:
509:
500:
470:
469:
456:
451:
434:
413:
396:anticonvulsants
391:
358:cherry-red spot
328:
284:genetic testing
272:
240:
238:Pathophysiology
201:the indigenous
183:
138:
98:
68:
17:
12:
11:
5:
1983:
1981:
1973:
1972:
1967:
1962:
1957:
1952:
1942:
1941:
1935:
1934:
1932:
1931:
1926:
1923:Wolman disease
1912:
1906:
1904:
1900:
1899:
1897:
1896:
1894:Batten disease
1891:
1886:
1880:
1878:
1872:
1871:
1868:
1867:
1865:
1864:
1862:Farber disease
1854:
1852:
1845:
1844:
1842:
1840:Krabbe disease
1833:
1828:
1819:
1817:
1816:
1815:
1812:leukodystrophy
1797:
1796:
1794:
1793:
1784:
1778:
1761:
1759:
1752:
1751:
1749:
1748:
1738:
1736:
1729:
1728:
1726:
1725:
1719:
1714:
1705:
1695:
1693:
1690:gangliosidoses
1677:
1665:
1664:
1646:
1644:
1643:
1636:
1629:
1621:
1612:
1611:
1608:
1607:
1595:
1594:
1592:
1588:
1587:
1584:
1583:
1572:
1561:
1550:
1535:
1520:
1504:
1499:
1498:
1496:
1495:Classification
1489:
1488:
1475:
1474:External links
1472:
1461:
1460:
1411:
1372:(8): 3979–83.
1352:
1301:
1266:
1237:
1198:(3): 550–563.
1178:
1172:978-0470016176
1171:
1145:
1102:
1077:
1058:(1): 139–145.
1042:
1023:(3): 328–333.
1007:
988:(1–2): 133–7.
968:
949:
924:Human Genetics
914:
881:Human Genetics
870:
849:
821:
800:(1): 338–345.
777:
762:
741:
717:
690:(4): 417–422.
684:Human Genetics
667:
647:
604:
577:(39): 1833–9.
560:
523:(4): 351–354.
498:
453:
452:
450:
447:
446:
445:
440:
433:
430:
412:
409:
390:
387:
378:
377:
373:
365:
327:
324:
271:
268:
239:
236:
223:Ashkenazi Jews
219:
218:
209:
199:
182:
179:
137:
134:
97:
94:
76:
75:
62:
56:
55:
51:
50:
42:
41:
28:
24:
23:
15:
13:
10:
9:
6:
4:
3:
2:
1982:
1971:
1968:
1966:
1965:Rare diseases
1963:
1961:
1958:
1956:
1953:
1951:
1948:
1947:
1945:
1930:
1927:
1924:
1920:
1916:
1913:
1911:
1908:
1907:
1905:
1901:
1895:
1892:
1890:
1887:
1885:
1882:
1881:
1879:
1877:
1873:
1863:
1859:
1856:
1855:
1853:
1851:
1846:
1841:
1837:
1834:
1832:
1829:
1827:
1823:
1820:
1818:
1813:
1810:
1809:
1808:
1803:
1798:
1792:
1788:
1785:
1782:
1779:
1777:
1773:
1770:
1769:phospholipid:
1766:
1765:Sphingomyelin
1763:
1762:
1760:
1758:
1757:sphingomyelin
1753:
1747:
1743:
1740:
1739:
1737:
1735:
1730:
1723:
1720:
1718:
1715:
1713:
1709:
1706:
1704:
1700:
1697:
1696:
1694:
1691:
1686:
1681:
1678:
1675:
1670:
1666:
1661:
1657:
1653:
1652:Inborn errors
1649:
1642:
1637:
1635:
1630:
1628:
1623:
1622:
1619:
1606:
1602:
1601:
1597:
1596:
1593:
1589:
1582:
1578:
1577:
1573:
1571:
1567:
1566:
1562:
1560:
1556:
1555:
1551:
1549:
1545:
1544:
1540:
1536:
1534:
1530:
1529:
1525:
1521:
1519:
1515:
1514:
1510:
1506:
1505:
1502:
1497:
1493:
1487:
1483:
1482:
1478:
1477:
1473:
1471:
1470:
1469:
1456:
1452:
1447:
1442:
1438:
1434:
1431:(7): 1201–5.
1430:
1426:
1422:
1415:
1412:
1407:
1403:
1398:
1393:
1388:
1383:
1379:
1375:
1371:
1367:
1363:
1356:
1353:
1348:
1344:
1340:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1305:
1302:
1297:
1293:
1289:
1285:
1281:
1277:
1270:
1267:
1256:on 2018-02-24
1255:
1251:
1247:
1241:
1238:
1233:
1229:
1224:
1219:
1215:
1211:
1206:
1201:
1197:
1193:
1189:
1182:
1179:
1174:
1168:
1164:
1160:
1156:
1149:
1146:
1141:
1137:
1133:
1129:
1125:
1121:
1117:
1113:
1106:
1103:
1092:on 2009-01-29
1091:
1087:
1081:
1078:
1073:
1069:
1065:
1061:
1057:
1053:
1046:
1043:
1038:
1034:
1030:
1026:
1022:
1018:
1011:
1008:
1003:
999:
995:
991:
987:
983:
975:
973:
969:
964:
960:
953:
950:
945:
941:
937:
933:
929:
925:
918:
915:
910:
906:
902:
898:
894:
890:
887:(3): 279–82.
886:
882:
874:
871:
859:
853:
850:
838:
834:
828:
826:
822:
817:
813:
808:
803:
799:
795:
791:
784:
782:
778:
773:
766:
763:
751:
745:
742:
730:
724:
722:
718:
713:
709:
705:
701:
697:
693:
689:
685:
678:
676:
674:
672:
668:
665:
661:
656:
654:
652:
648:
643:
639:
635:
631:
627:
623:
619:
615:
608:
605:
600:
596:
592:
588:
584:
580:
576:
572:
564:
561:
556:
552:
548:
544:
539:
534:
530:
526:
522:
518:
514:
507:
505:
503:
499:
494:
490:
486:
482:
478:
474:
467:
465:
463:
461:
459:
455:
448:
444:
441:
439:
436:
435:
431:
429:
425:
417:
410:
408:
405:
400:
397:
388:
386:
384:
374:
371:
366:
363:
359:
355:
351:
347:
343:
339:
334:
333:
332:
325:
323:
320:
314:
311:
306:
301:
297:
293:
289:
285:
281:
277:
269:
267:
264:
262:
258:
254:
250:
247:
246:
237:
235:
231:
228:
224:
217:
213:
210:
208:
204:
200:
198:
194:
193:
192:
189:
186:
180:
178:
176:
170:
165:
163:
159:
154:
150:
145:
143:
135:
133:
129:
127:
123:
119:
115:
111:
107:
103:
95:
93:
91:
86:
82:
72:
66:
65:Endocrinology
63:
61:
57:
52:
48:
43:
40:
36:
32:
29:
25:
20:
1807:sulfatidoses
1768:
1711:
1598:
1574:
1563:
1552:
1537:
1522:
1507:
1479:
1465:
1464:
1428:
1424:
1414:
1369:
1365:
1355:
1314:
1310:
1304:
1279:
1275:
1269:
1258:. Retrieved
1254:the original
1249:
1240:
1195:
1191:
1181:
1154:
1148:
1118:(2): 241–9.
1115:
1111:
1105:
1094:. Retrieved
1090:the original
1080:
1055:
1051:
1045:
1020:
1016:
1010:
985:
981:
962:
958:
952:
930:(1): 12–17.
927:
923:
917:
884:
880:
873:
862:. Retrieved
852:
841:. Retrieved
837:the original
797:
793:
771:
765:
754:. Retrieved
744:
733:. Retrieved
687:
683:
617:
613:
607:
574:
570:
563:
520:
516:
479:(6): 283–8.
476:
472:
426:
422:
401:
392:
379:
362:organomegaly
342:motor skills
329:
315:
309:
296:enzyme assay
273:
265:
260:
243:
241:
232:
225:may reflect
220:
207:Saskatchewan
190:
187:
184:
169:chromosome 5
166:
146:
139:
130:
106:gangliosides
99:
80:
79:
38:
34:
30:
1850:sphingosine
1699:Ganglioside
1685:ganglioside
172:exons 1–5.
27:Other names
1944:Categories
1722:AB variant
1576:DiseasesDB
1260:2018-02-23
1096:2009-05-03
864:2009-05-03
843:2009-05-03
756:2009-05-03
735:2009-05-03
449:References
313:mutation.
300:urinalysis
151:on the 14
1884:Infantile
1822:Sulfatide
1802:sulfatide
1734:globoside
1282:: 354–6.
1214:0022-2275
599:260064612
517:FEBS Lett
443:Globoside
389:Treatment
350:paralysis
270:Diagnosis
197:Argentina
162:Lysosomes
158:lysosomes
122:pneumonia
60:Specialty
1858:Ceramide
1674:ceramide
1600:Orphanet
1296:13957544
1232:29358305
1140:41447979
1132:15159655
1037:16569321
1002:11880123
944:10982028
712:39688704
662:(OMIM):
555:84542601
547:11947222
473:Life Sci
432:See also
346:dementia
1570:D012497
1455:6226523
1374:Bibcode
1347:8473726
1339:5793973
1319:Bibcode
1311:Science
1223:5832932
1072:8162015
909:9666991
901:8076944
807:1685463
704:7557963
642:1735733
634:5124584
591:5679107
525:Bibcode
493:5651108
411:History
338:muscles
110:enzymes
1781:type C
1559:268800
1533:E75.01
1453:
1446:555256
1443:
1425:EMBO J
1404:
1397:392913
1394:
1345:
1337:
1294:
1230:
1220:
1212:
1169:
1138:
1130:
1070:
1035:
1000:
965:: A48.
942:
907:
899:
816:414620
814:
804:
710:
702:
640:
632:
597:
589:
553:
545:
491:
383:ataxia
370:autism
348:, and
319:embryo
276:biopsy
216:Cyprus
149:codons
142:genome
136:Causes
67:
1903:Other
1800:From
1755:From
1732:From
1683:From
1581:29469
1548:330.1
1528:10-CM
1518:E75.0
1486:NINDS
1406:99746
1343:S2CID
1136:S2CID
905:S2CID
708:S2CID
638:S2CID
595:S2CID
551:S2CID
376:span.
352:. An
326:Types
288:cells
280:liver
203:MĂ©tis
153:exons
124:, or
1672:(to
1565:MeSH
1554:OMIM
1543:9-CM
1451:PMID
1402:PMID
1335:PMID
1292:PMID
1228:PMID
1210:ISSN
1167:ISBN
1128:PMID
1068:PMID
1033:PMID
998:PMID
940:PMID
897:PMID
812:PMID
700:PMID
630:PMID
587:PMID
543:PMID
489:PMID
310:HEXB
261:HEXB
255:and
249:gene
245:HEXB
1876:NCL
1848:To
1654:of
1605:796
1539:ICD
1524:ICD
1509:ICD
1484:at
1441:PMC
1433:doi
1392:PMC
1382:doi
1327:doi
1315:165
1284:doi
1218:PMC
1200:doi
1159:doi
1120:doi
1060:doi
1025:doi
990:doi
986:318
932:doi
928:107
889:doi
802:PMC
692:doi
622:doi
579:doi
533:doi
481:doi
354:eye
305:DNA
294:),
205:in
120:),
37:or
1946::
1860::
1838::
1824::
1789::
1767::
1744::
1701::
1650::
1603::
1579::
1568::
1557::
1546::
1531::
1516::
1513:10
1449:.
1439:.
1427:.
1423:.
1400:.
1390:.
1380:.
1370:75
1368:.
1364:.
1341:.
1333:.
1325:.
1313:.
1290:.
1280:70
1278:.
1248:.
1226:.
1216:.
1208:.
1196:59
1194:.
1190:.
1165:.
1157:.
1134:.
1126:.
1116:27
1114:.
1066:.
1054:.
1031:.
1021:12
1019:.
996:.
984:.
971:^
963:37
961:.
938:.
926:.
903:.
895:.
885:94
883:.
824:^
810:.
798:30
796:.
792:.
780:^
720:^
706:.
698:.
688:96
686:.
670:^
650:^
636:.
628:.
618:49
616:.
593:.
585:.
575:93
573:.
549:.
541:.
531:.
519:.
515:.
501:^
487:.
475:.
457:^
282:,
128:.
33:,
1925:)
1921:/
1917:(
1814:)
1805:(
1783:)
1774:(
1724:)
1710:(
1692:)
1688:(
1676:)
1662:)
1658:(
1640:e
1633:t
1626:v
1541:-
1526:-
1511:-
1501:D
1457:.
1435::
1429:2
1408:.
1384::
1376::
1349:.
1329::
1321::
1298:.
1286::
1263:.
1234:.
1202::
1175:.
1161::
1142:.
1122::
1099:.
1074:.
1062::
1056:3
1039:.
1027::
1004:.
992::
946:.
934::
911:.
891::
867:.
846:.
818:.
759:.
738:.
714:.
694::
644:.
624::
601:.
581::
557:.
535::
527::
521:4
495:.
483::
477:7
Text is available under the Creative Commons Attribution-ShareAlike License. Additional terms may apply.