/ GM2 21 134 Gustavo H. B. Maegawa, MD a,b,c, Tracy Stockley, PhD d, Michael Tropak, PhD b, Brenda Banwell, MD e, Susan Blaser, MD f, Fernando Kok, MD, PhD g, Roberto Giugliani, MD, PhD h, Don Mahuran, PhD b and Joe T.R. Clarke, MD, PhD a,b a Divisions of Clinical and Metabolic Genetics; b Research Institute, Hospital for Sick Children; c Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada; d Paediatric Laboratory Medicine; e Neurology; f Departments of Paediatrics, Diagnostic Imaging; g Centro do Genoma Humano, University of Sao Paulo, Sao Paulo, Brazil; h Medical Genetics Service, Hospital de Clinicas de Porto Alegre, Porto Alegre, Brazil GM2 β - GM2 GM2 (juvenile GM2 gangliosidosis); β - 21 GM2 (β-hexosaminidase deficiency); ( 15 Tay-Sachs 6 Sandhoff ) Tay-Sachs (Tay-Sachs 134 disease); Sand-hoff (Sandhoff disease); β - (lysosomal storage (5.3 4.1) disease) 8.4 y (66.7%) (52.4%) (28.6%) (28.6%) (7.1 jgm2 = juvenile GM2 gangliosidosis 5.6) (6.2 5.5) y OMIM = Online Mendelian Inheritance in Man (7.0 5.6) (5.6 5.3) y TSV = Tay-Sachs variant (10.6 7.4) (11.1 SV = Sandhoff variant 7.7) (14.6 9.7) Sandhoff CT = computed tomography MUG = 4-methylumbelliferyl-β- Tay-Sachs N-acetyl glucosaminide MRI (52.9%) MUGS = 4-methylumbelliferyl-β- 14.5 N-acetylglucosaminide-6-sulfate PEDIATRICS 2007 7 2 7 681
Tay-Sachs R178H R499H Address correspondence to Joe T. G269S R. Clarke, MD, PhD, Division of Clinical and Metabolic Genetics, Hospital for Sick Children, 555 University W474C GM2 Ave, Toronto, Ontario, Canada M5G 1X8. E-mail: joe.clarke@sickkids.ca Tay-Sachs Sandhoff Tay-Sachs HEXA GM2 (jgm2) ( GM2 ) GM2 GM2 AB GM2 (Online Mendelian Inheritance in (OMIM No.272750) [1, 2] Man OMIM) No.230700 Tay-Sachs (TSV) 1 / 201 000 1 / 222 000 β - A β - A B GM2 1 / 384 000 1 / 422 000 β - [3] TSV (1 / 30) β - A β - B β - (1 / 14) A α β (1 / 300) [4] HEXA (15q23-q24) HEXB (5q13) TSV GM2 [5, 6] β-n- β - B β (β 2 ) GM2 GM2 α HEXA β - 6 mo [7] A GM2 3 5 Tay-Sachs (OMIM No.272800) HEXB GM2 ( β ) (β - A B) Sandhoff [3] Sandhoff (SV) [1, 8 22] (OMIM No.268800) GM2 Sandhoff Tay-Sachs GM2 β - A 682 MAEGAWA et al
[11, 13, 20, 21] jgm2 21 17 1 [21, 23] MRI CT 21 / GM2 jgm2 [1, 8, 9, 11 14, 18, 20, 22, 24 82] GM2 134 jgm2 4 - - β - N - TSV (MUG) 4- -β-n- SV HEXA HEXB -6- (MUGS) [5, 83] ( ) β - MUG β - B β - A β - MUGS β - A (1) (2) TSV B1 DNA TSV SV (3) / HEXA HEXB 84 90 ( 7 8 20) DNA 21 jgm2 1968 1 2006 1 134 (University of Sao Paulo) 8.4 y ( 1.1 23.5 y) (n = 8) (Hospital for Sick Children) (n = 13) jgm2 1 18 1968 1 2006 1 1 18 GM2 PubMed juvenile GM2 gangliosidosis juvenile Tay-Sachs PEDIATRICS 2007 7 2 7 683
1 jgm2 (n = 21) (n = 134) (n = 155) ( ) 0 y ( ) 0 y ( ) 0 y 0 0 17.0 (5.4) 7 0 0 33.0 (5.1) 40 0 0 33.0 (5.2) 47 0 0 13.0 (3.6) 10 0.5 0 28.0 (5.2) 54 0.5 0 35.5 (4.4) 64 0 0 11.0 (3.9) 9 0 0 25.0 (4.6) 34 0 0 25.0 (4.2) 43 0.5 0 17.0 (4.7) 11 0 0 28.0 (4.2) 31 0 0 28.0 (4.4) 42 1.5 0 6.0 (2.8) 8 9.5 0 31.0 (12) 32 6.0 0 31.0 (7.4) 40 2.5 0 10.0 (5.9) 6 3.2 0 14.5 (7) 4 2.5 0 14.5 (6.4) 10 2.7 0.5 5.0 (2.8) 8 2.0 0 29.5 (4.2) 36 1.4 0 29.5 (3.5) 44 2.7 0.1 15.0 (5.3) 12 3.8 0 13.0 (4.7) 18 3.0 0 15.0 (5) 30 3.4 0 12.0 (4.7) 15 3.5 0 35.5 (8.1) 63 3.4 0 35.5 (6.4) 78 3.5 0 2.0 (3.7) 7 3.0 0 33.0 (8.6) 24 3.0 0 33.0 (6.1) 31 / 3.7 0 17.0 (4.5) 15 3.0 0 7.0 (3.5) 10 3.0 0 17.0 (4) 25 4.0 0 16.0 (7.7) 10 8.5 0 30.0 (11.2) 39 8.5 0 30.0 (9.4) 49 / 4.0 0 22.0 (10.5) 7 2.5 0 17.5 (5) 11 2.5 0 22.0 (7.7) 18 5.8 0 18.0 (6.9) 12 7.0 0 31.0 (12.4) 37 6.0 0 31.0 (9.6) 49 5.8 1 28.0 (9.3) 6 2.3 0 28.0 (8.3) 16 2.6 0 28.0 (8.8) 22 7.5 0 13.0 (8.4) 10 4.0 0 28.0 (9.2) 31 4.5 0 28.0 (8.8) 41 y 684 MAEGAWA et al
2 jgm2 (n = 21) a (n = 134) b (%) x s ( ) / y (%) x s ( ) / y 21 (100) 7.1 6.9 (1.5 27.0) 118 (88) 11.0 7.0 (1.0 39.0) 21 (100) 7.0 5.6 (2.0 19.0) 104 (77.6) 8.4 7.9 (1.0 40.0) 20 (95.3) 6.8 5.6 (1.5 20.0) 83 (62.4) 7.4 6.1 (1.0 35.0) 17 (81) 8.5 4.5 (2.8 16.0) 73 (54.5) 12.2 10.7 (2.0 40.0) 17 (80.9) 7.8 7.4 (1.6 26.0) 70 (52.2) 5.8 5.6 (1.0 32.0) / 16 (76.2) c 8.6 6.8 (2.0 27.0) 11 (8.2) 6.4 3.0 (1.0 10.0) 14 (66.7) d 10.6 7.4 (2.0 27.0) c 43 (32.3) 17.8 11.2 (2.3 40.0) 13 (61.9) d 11.1 7.7 (1.75 27.0) d 42 (31.3) 17.6 10.4 (1.3 38.0) 13 (61.9) d 13.6 6.0 (3.0 21.0) 47 (35.1) 12.1 8.4 (1.2 35.0) 12 (57.1) c 8.5 7.4 (2.0 25.0) 19 (14.1) 9.0 6.0 (2.1 22.0) 11 (52.4) d 5.7 3.0 (2.0 11.0) c 36 (26.9) 17.6 10.2 (2.2 40.0) 11 (52.4) c 10.9 5.8 (2.0 18.0) 6 (4.5) 7.4 3.9 (3.0 13.0) / 11 (52.4) c 14.6 9.7 (5.5 28.0) 16 (11.9) 8.2 5.3 (3.0 22.5) 10 (47.6) d 8.1 5.7 (1.5 17.0) 25 (18.6) 12.7 10.7 (1.3 40.0) 9 (42.8) c 8.1 4.1 (3.0 15.5) 6 (4.5) 8.9 9.4 (2.0 27.0) 8 (38.1) 6.0 2.0 (2.5 8.0) d 32 (23.9) 10.8 8.4 (1.5 40.0) 8 (38.1) 8.0 5.1 (2.0 7.5) 45 (33.6) 6.7 6.4 (1.5 32.0) 6 (28.6) 11.9 10.9 (2.5 30.0) 20 (14.9) 12.4 12.2 (1.6 40.0) ( ) 3 (14.3) c 5.3 3.1 (2.0 8.0) 3 (2.2) 17.3 8.1 (10.0 26.0) a (12.3 10.7) b (16.1 11.2) c P 0.001 d P 0.05 disease juvenile Sandhoff disease Tay-Sachs disease Sandhoff disease GM2 gangliosidosis 21 30 ( 30 ) 21 134 Kaplan-Meyer χ 2 Student s t 134 21 15 10 11 15 (71.4%) jgm2 TSV 6 (28.6%) jgm2 SV ( 1 3) (19.3 12.5) ( 2.7 37.2 ) PEDIATRICS 2007 7 2 7 685
(12.3 10.7) 21 jgm2 TSV 5 96 (71.6%) jgm2 SV 27 (20.1%) 4 3 134 2 2 2 AB jgm2 [1] 9 [24, 25, 29 32, 34] 2 1 jgm2 9 (6.7%) 1968 1973 1 1 GM2 ( ) [24 26, 29 32, 34, 91] 134 134 (16.1 11.2) ( 1.75 43 ) 134 70 (52.2%) 64 (47.8%) jgm2 TSV (56.3%) jgm2 SV 22.6% (30 / 134 ) 3 jgm2 Tay-Sachs Sandhoff (n = 21) (n = 134) TSV (n = 15) SV (n = 6) TSV (n = 96) SV (n = 27) _ x s / y 5.4 3.5 4.8 4.4 5.8 4.3 5.0 3.3 _ x s / y 13 12.6 10.5 3.3 17.2 11.2 15.9 11.8 / 1.0 1.0 1.23 a 0.93 / n (%) 0 1 (16.7) 11 (11.4) 14 (51.8) b / n (%); / _ x s 15 (100); 7.9 7.8 6 (100); 4.8 3.4 88 (91.6); 7.5 6.6 20 (74.1); 7.4 8.4 15 (100); 6.5 5.7 6 (100); 8.4 5.6 92 (95.8); 9.1 7.9 19 (70.4); 7.5 9.1 13 (86.7); 6.5 5.9 6 (100); 7.2 5.3 60 (62.5); 7.7 6.2 15 (55.5); 8.0 8.4 12 (80); 7.1 4.5 5 (93.4); 9.2 3.8 51 (53.1); 14.2 11.5 15 (55.5); 9.0 7.9 13 (86.7); 7.4 7.7 3 (50); 9.2 6.9 45 (46.5); 7.1 6.5 15 (55.5); 3.9 2.3 / 10 (66.7); 8.8 8.1 6 (100); 8.8 8.0 6 (6.2); 7.6 2.8 5 (18.5); 5.7 3.7 a 8 (53.3); 9.0 8.5 6 (100); 12.7 5.4 32 (33.4); 20.5 10.9 7 (25.9); 11.1 9.8 a 9 (60); 8.7 5.8 4 (66.7); 16.5 9.5 33 (34.4); 18.9 10.2 7 (25.9); 12.8 9.6 7 (46.7); 15.2 6.0 6 (100); 11.7 5.9 a 35 (36.4); 13.2 8.2 8 (29.6); 10.1 9.6 8 (53.3); 4.7 2.3 b 4 (66.7); 16.1 8.5 12 (12.5); 10.4 6.7 4 (14.8); 7.7 4.4 8 (53.3); 5.0 2.8 3 (50); 7.5 3.5 28 (29.2); 19.4 10.1 6 (22.3); 11.2 6.5 7 (46.7); 8.6 4.8 4 (66.7); 15.0 5.3 a 2 (2.1); 5.7 2.5 5 (18.5); 8.2 4.6 b / 7 (46.7); 3.5 4.8 b 4 (66.7); 19.5 10.2 10 (10.5); 5.7 3.7 5 (18.5); 9.1 8.5 9 (60); 7.1 5.0 1 (16.7); 17 17 (17.8); 13.8 11.2 6 (22.3); 11.7 10.8 6 (40); 9.7 4.2 3 (50); 4.8 1.0 4 (4.2); 10.0 11.7 NR; NR 7 (46.7); 6.6 1.7 2 (33.3); 4.2 2.5 24 (25.0); 11.0 10.6 5 (18.5); 13.3 14.7 7 (46.7); 5.2 2.1 1 (16.7); 4 1 (1.0); 7.5 7.4 7 (25.9); 5.4 4.7 4 (26.7); 7.2 6.8 2 (33.3); 16.7 9.2 2 (2.1); 14.3 12.9 3 (11.1); 5.4 3.3 ( ) 1 (6.7); 2 2 (33.3); 7.0 1.4 a 2 (2.1); 26 7.0 a 1 (3.7); 10.0 NR a P 0.05 b P 0.001 686 MAEGAWA et al
4 β - β - β - β - / nmol B / nmol mg B / % A / % mg h -1 h -1 1 2 1 2 TSV HEXA 1 2 021 (l) 1 778 (l) 88 12 c.1496g A / c.1278instatc R499H 2 681 (l) 646 (l) 95 5 c.1496g A / c.1278instatc R499H 3 739 (l) 716 (l) 97 3 c.1496g A / c.1073 1G A R499H 9 392 (l) 349 (l) 89 11 c.1422g C / c.1278instatc W474C 10 389 (l) 334 (l) 86 14 c.1422g C / c.1278instatc W474C 11 1 173 (l) 1 009 (l) 86 14 c.1496g A / c.1073 1G A R499H 12 798 (p) 487 (p) 61 39 a c.533g A / c.1510delc R178H 13 1 253 (p) 714 (p) 57 43 b c.533g A / c.533g A R178H R178H 14 647 (p) 355 (p) 55 45 c c.533g A / c.681c G R178H Y227 15 7 664 (f) 7 334 (f) 95.7 4.3 c.1496g A / c.1330 1G A R499H 16 1 166 (p) 1 003 (p) 86 14 c.805g A / c.1278instatc G269S 17 1 096 (p) 919 (p) 84 16 c.805g A / c.1278instatc G269S 18 870 (p) 835 (p) 96 4 c.805g A / c.1278instatc G269S 19 465 (p) 251 (p) 54 46 d c533g A / c.1495c T R178H R499C 21 1 202 (l) 1 166 (l) 97 3 c.805g A / c.672 1G A G269S SV HEXA 4 82 (l) ND (l) 0 100 c.1514g A / IVS11 5G A R505Q 5 51 (l) ND (l) 0 100 c.1514g A / IVS11 5G A R505Q 6 126 (l) 21 (l) 16.7 83.3 c.410g A / c.410g A C137Y C137Y 7 36 (p) ND (p) 0 100 c.796t G / IVS12 26G A Y266D 8 230 (f) ND (f) 0 100 c.796t G / IVS12 26G A Y266D 20 65 (l) ND (l) 0 100 c.1057g C / IVS12 26G A G353R T Hex (MUG) β - (nmol mg -1 h -1 ) β - A β - B B1 Tay-Sachs β - A ( 12 14 19) (MUGS) β - A (p) β- (2 400 488) nmol ml -1 h -1 β - B 30% 45% (l) ( β - 961 1 576 nmol mg -1 h -1 β - B 30% 45%) (f) ( β - 4 900 21 000 nmol mg -1 h -1 β - B a d 30% 45%) ND β - A 4.8 14.5 6.7 9.1 nmol mg -1 h -1 ( 150 390 nmol mg -1 h -1 ) 11.9% (16 / 134 ) 32 (23.9%) (9 ) (6 ) (5 ) (4 ) β - (4 ) 9 TSV β - A SV PEDIATRICS 2007 7 2 7 687
14 11 11 6 / 6 7 4 4 / 5 / 3 / 16 / 1 1 8 2 2 11 9 6 4 50 49 39 / 78 0 30 60 90 1 jgm2 (n = 21) (n = 134) [5, 83] β - ( 4) ( ) [94] 15 TSV 11 HEXA ( 1 2 9 10 16 18) 1278insTATC 7 3 (GGDE) HEXA R499H 134 (n = 5) R178H (n = 5) Y277X 7 1 11 HEXA 1 (R178H / R178H) 6 SV 5 2 ( IVS12-26G A R505Q) [7, 12, 92, 93] 1 ( 20) G353R 20 β - [95] (5.3 4.1) ( 1.5 15 ) 1 ( 2) (15 / 21 β C137Y 71.4%) 3 6 (28.6%) 2 5 (23.5%) 1 [94] Y266D 21 2 688 MAEGAWA et al
(95.3%) (80.9%) 2 1 10 6.1 1 3.4 GM2 ( 14) 0 3 jgm2 (x _ s ) 134 (5.4 4.0) ( 1 17 ) ( 2) 70 (P 0.001) ( 3) SV (52.2%) 2 13 /y TSV (P 0.05) (9.7%) 3 (P (58.2%) (37.3%) 0.05) ( 3) jgm2 (36.5%) (29.1%) TSV SV (11.9%) TSV SV ( 1) 10 SV [11, 13, 24, 35, 36, 38, 42, 64] (15.4%) TSV / [34, 36] 2 4 SV ( [1, 18, 34, 65, 70] (4.6%) 3) 20 9.6 11.5 (n =14) (n =14) (n =7) TSV SV TSV SV 21 20 [7] jgm2 1 20 TSV (12.3 10.7) ( 2.5 36.9 ) SV (7.5 8.3) y ( 0.3 26.8 y) 18 jgm2 /y 12 6 3.8 6.2 0 (n =12) (n =12) (n =8) 2 jgm2 (x _ s ) 9.4 21 3.4 y ( 0 12 y) 134 3.5 y ( 0 35.5 y) ( 3) 3 (1) ( ) (2) ( ) PEDIATRICS 2007 7 2 7 689
1.0 0.6 0.2 0 0 20 40 4 (3) ( ) 2 12 (57.4%) 2.4 4 y ( 0.5 7.0 y) TSV HEXA 3.2 y ( 0.2 10 y) SV HEXB (5.6 5.3) y ( 1 14 y) (2) 3 (1) 19 21) (3) 2 14 TSV 1 HEXA 1 R178H 3.5 y ( 0.3 8.0 y) 7 ( 12 14 19) R178H β - A B1 [75, 96, 97] 2.6 y ( 0.5 8.0 y) 7 1.8 ( 1.5 2.5 ) 1.4 y (6.2 5.5) y ( 1 16 y) 1 / 3 + (n =20) (n =31) /y jgm2 (10.5 5.5) ( 3.9 26.0 ) 1 4 31 20 (40%) 104 (19.0 2.1) y (95% 14.9 23.0) 14.5 y (95% 11.7 17.3) [1, 20, 25, 27, 29, 34, 38, 42, 56, 74, 91] (13 43.4%) 1 (neuroleptic malignant syndrome) [8] 1 [34] 11 [13, 20, 24, 27, 28, 36, 40, 45, 56, 65, 68, 70] ( 1 3 9 12 14 1.3 y ( 13 14 19) 134 30 1.2 y 7 [1, 8, 11, 13, 20, 24, 25, 27, 34, 36, 38, 42, 45, 56, 65, 68 70, 74, 91] 4 R178H 690 MAEGAWA et al
R178H / 21 17 1 MRI (9.7 7.9) ( 1.8 28.6 ) 6 5 ( 1 3 11 15) (35.3%) (5.1 1.8) ( 1 HEXA 1 R499H 1.8 6.9 ) 2.6 ( 2.0 3.0 ) ( ) 4 3.0 y R499H (23.5%) (11.4 7.3) ( 5.3 α 15.6 ) 5 [98] (29.4%) (18.6 6.4) ( 4.8 y 6 28.6 ) 1 3.3 MRI 1 / 5.3 CT 5 (13.0 HEXA 1 G269S 4.2) ( 6.9 16.0 ) 4 ( 16 18 21) 4 N- G269S TSV [4] 2% 134 35 [99] β - A α β (28.7 10.7) ( 16 42 ) 9.0 ( 6 11 ) 18 CT (21.4 y) 14 MRI 1 [38] / 2 W474C 42.8% (15 / 35 ) ( 9 10) 10 (18.0 13.3) ( 4 42 ) 15 20% (7 / 35 ) W474C (8.2 4.2) ( 2.5 15 1 α α ) [11, 13, 70] 2 8 30 MRI [100] [52, 81] W474C 17.1% (6 / 35 3.9 ) y HEXA G269S W474C (7.5 7.9) ( 2.7 20 ) 1 ( 17) G269S 16 y jgm2 SV 21 jgm2 134 PEDIATRICS 2007 7 2 7 691
( 1) jgm2 ( 1) 21 jgm2 134 [7] 2 10 GM2 / [8, 10, 39, 46, 47, 49, 52, 55, 59, 60, 67, 76] jgm2 ( 2) 1 18 jgm2 TSV SV 21 TSV SV R178H 5 SV / HEXA ( 12 14 19) B1 TSV TSV SV [96, 97] ( 3) (founder effect) HEXA ( 1) TSV 1278ins [2, 4] TACT / 3 3 3.5 ( 1 2 9 10 16 17) 692 MAEGAWA et al
SV 1 MRI / N - 101, 102 GM2 jgm2 21 jgm2 30 Kaplan-Meyer ( 4) jgm2 jgm2 10 1 / 4 ( ) HEXA R178H TSV (c. 1278insTATC c.1073 1G A) 1 Inui K, et al. Am J Hum Genet 1983;35:551 564 2 Mahuran DJ. Biochim Biophys Acta 1999;1455:105 138 3 Meikle PJ, et al. JAMA 1999;281:249 254 HEXA 4 Kaback MM. Eur J Pediatr 2000;159(Suppl 3):S192 S195 R499H 5 Kaback MM, et al. Prog Med Genet 1974;10:103 134 6 Triggs-Raine BL, et al. N Engl J Med 1990;323:6 12 7 Gravel R, et al. The GM2 gangliosidosis. In: Scriver CR, et al, eds. The Metabolic and Molecular Basis of Inherited Disease. 8th ed. G269S W474C New York, NY: McGraw-Hill; 2001:3827 3876 8 Rapin I, et al. Arch Neurol 1976;33:120 130 9 Argov Z, et al. Ann Neurol 1984;16:14 20 HEXA 10 Navon R, et al. Am J Med Genet 1986;24:179 196 11 Specola N, et al. Neurology 1990;40:145 150 12 Mitsuo K, et al. J Neurol Sci 1990;98:277 286 13 Maia M, et al. Neuropediatrics 1990;21:18 23 14 Boustany RM, et al. Ann Neurol 1991;29:104 107 15 Nishimoto J, et al. J Biol Chem 1991;266:14306 14309 16 Yuksel A, et al. Pediatr Neurol 1999;21:562 565 17 Fox J, et al. Acta Neuropathol (Berl) 1999;97:57 62 18 Unnikrishnan AG, et al. Indian Pediatr 2001;38:89 92 19 Chow GC, et al. Pediatr Neurol 2001;25:59 61 20 Hendriksz CJ, et al. J Inherit Metab Dis 2004;27:241 249 21 Neudorfer O, et al. Genet Med 2005;7:119 123 PEDIATRICS 2007 7 2 7 693
22 Navon R, et al. Ann Neurol 1997;41:631 638 23 Zaroff CM, et al. Neurology 2004;62:2283 2286 24 Bernheimer H, et al. Wien Klin Wochenschr 968;80:163 164 passim 25 Derry DM, et al. Neurology 1968;18:340 348 26 Derry DM, et al. Exp Brain Res 1968;5:32 44 27 Suzuki K, et al. Neurology 1970;20:190 204 28 Suzuki Y, et al. Neurology 1970;20:848 851 29 Okada S, et al. J Pediatr 1970;77:1063 1065 30 De Negri M, et al. Acta Neurol (Napoli) 1970;25:547 550 31 Menkes JH, et al. Arch Neurol 1971;25:14 22 32 Borri PL, et al. Acta Neurol Belg 1971;71:309 318 33 Buxton P, et al. J Neurol Neurosurg Psychiatry 1972;35:685 692 34 Brett EM, et al. Arch Dis Child 1973;48:775 785 35 Spence MW, et al. Pediatr Res 1974;8:628 637 36 Andermann EAF, et al. Can J Neurol Sci 1976;3:150 153 37 MacLeod PM, et al. Neurology 1977;27:571 573 38 Brandt S, et al. Acta Neurol Scand 1977;56:587 602 39 Goldie WD, et al. Ann Neurol 1977;2:156 158 40 Andermann E, et al. Prog Clin Biol Res 1977;18:161 188 41 Wood S. Hum Genet 1978;41:325 329 42 Felding I, et al. Neuropadiatrie 1978;9:74 83 43 Chester MA, et al. Hum Hered 1979;29:124 128 44 Johnson WG, et al. Am J Hum Genet 1980;32:508 518 45 Goldman JE, et al. Acta Neuropathol (Berl) 1980;52:189 202 46 Willner JP, et al. Neurology 1981;31:787 798 47 Navon R, et al. Neurology 1981;31:1397 1401 48 Johnson WG, et al. Ann Neurol 1982;11:11 16 49 Kolodny EH, et al. Neurology 1982;32:A81 A82 50 Meek D, et al. Ann Neurol 1984;15:348 352 51 Charrow J, et al. Clin Genet 1985;27:78 84 52 Mitsumoto H, et al. Ann Neurol 1985;17:378 385 53 Mantovani JF, et al. Dev Med Child Neurol 1985;27:664 667 54 Parnes S, et al. Arch Neurol 1985;42:1176 1180 55 Oates CE, et al. Eur Neurol 1986;25(2):154 159 56 Adams C, et al. Dev Med Child Neurol 1986;28:236 243 57 Cashman NR, et al. Ann Neurol 1986;19:568 572 58 Hardie RJ, et al. J Neurol Neurosurg Psychiatry 1988;51:446 447 59 Lichtenberg P, et al. Br J Psychiatry 1988;153:387 389 60 Rubin M, et al. J Neurol Sci 1988;87:103 119 61 Goebel HH, et al. Pediatr Res 1989;25:89 93 62 Nakano R, et al. Rinsho Shinkeigaku 1989;29:1032 1038 63 Thomas PK, et al. J Neurol Neurosurg Psychiatry 1989;52:1103 1106 64 Tanaka A, et al. Am J Hum Genet 1990;46:329 339 65 Paw BH, et al. J Biol Chem 1990;265:9452 9457 66 dos Santos MR, et al. Am J Hum Genet 1991;49:886 890 67 Barnes D, et al. J Neurol Neurosurg Psychiatry 1991;54:1112 1113 68 Suzuki K, et al. Dev Neurosci 1991;13:288 294 69 Nardocci N, et al. Mov Disord 1992;7:64 67 70 Harmon DL, et al. J Med Genet 1993;30:123 128 71 Streifler JY, et al. Neurology 1993;43:2055 2058 72 Hurowitz GI, et al. J Neuropsychiatry Clin Neurosci 1993;5:30 36 73 Richard MM, et al. Biochem Mol Med 1995;55:74 76 74 Philippart M, et al. Neurochem Res 1995;20:1323 1328 75 Ribeiro MG, et al. J Med Genet 1996;33:341 343 76 De Gasperi R, et al. Neurology 1996;47:547 552 77 Hund E, et al. J Neurol Sci 1997;145:25 31 78 Beck M, et al. Eur J Pediatr 1998;157:866 867 79 Eiris J, et al. Rev Neurol 1999;29:435 438 80 Felderhoff-Mueser U, et al. J Child Neurol 2001;16:377 380 81 Grosso S, et al. J Neurol 2003;250:17 21 82 Van Hoof F, et al. Adv Exp Med Biol 1972;19:343 350 83 Lowden JA, et al. Clin Chem 1973; 19:1345 1349 84 Bapat B, et al. FEBS Lett 1988;237:191 195 85 Neote K, et al. Genomics 1988;3:279 286 86 Neote K, et al. J Clin Invest 1990;86:1524 1531 87 Brown CA, et al. Biochim Biophys Acta 1992;1180:91 98 88 McInnes B, et al. Biochim Biophys Acta 1992;1138:315 317 89 McInnes B, et al. J Clin Invest 1992;90:306 314 90 Stockley TL, et al. Methods Mol Biol 2003; 217:131 141 91 Volk BW, et al. Arch Pathol 1969;87:393 403 92 Nakano T, et al. J Biol Chem 1989;264:5155 5158 93 Dlott B, et al. J Biol Chem 1990;265:17921 17927 94 Mark BL, et al. J Mol Biol 2003;327:1093 1109 95 Henrissat B, et al. Biochem J 1993;293:781 788 96 Kytzia HJ, et al. J Biol Chem 1985; 260:7568 7572 97 Ohno K, et al. J Neurochem 1988;50:316 318 98 Matsuzawa F, et al. J Hum Genet 2003;48:582 589 99 Paw BH, et al. Proc Natl Acad Sci U S A 1989;86:2413 2417 100 Petroulakis E, et al. Hum Mutat 1998;11:432 442 101 Inglese M, et al. AJNR Am J Neuroradiol 2005;26:2037 2042 102 Aydin K, et al. Pediatr Radiol 2005;35:1081 1085 PEDIATRICS 2006;118(5):e1550 e1562 694 MAEGAWA et al