Table 1.
Neurodevelopmental Outcomes and Growth at 36 mos of age (or at Death) after Copper Histidine Treatment in Menkes disease.
| Subject | Gross motor (mos) | Fine motor (mos) | Personal social (mos) | Language (mos) | Weight (centile) | Length (centile) | OFC (centile) | ATP7A mutation | Death ≤3 yrs |
|---|---|---|---|---|---|---|---|---|---|
| Group I | |||||||||
| I-0126 | 3 | 4 | 6 | 6 | 0 | 0 | 0 | IVS8 AS dup5 | |
| I-0226 | 2 | 2 | 2 | 2 | 0 | 0 | 0 | IVS8 AS dup5 | |
| I-0318,28 | 1 | 1 | 1 | 1 | 10 | 0 | 25 | R201X | D |
| I-0412 | 2 | 2 | 2 | 3 | 0 | 0 | 0 | Q724H | |
| I-05 | 1 | 1 | 1 | 2 | 0 | 0 | 10 | 4195del4 | D |
| I-06 | 1 | 1 | 1 | 1 | 10 | 5 | 10 | 2926/7GG>TT | D |
| I-07 | 1 | 1 | 1 | 1 | 15 | 10 | 0 | 2926/7GG>TT | D |
| I-08 | 1 | 2 | 1 | 1 | 0 | 40 | 0 | IVS6 DS,+1g>a | D |
| I-09 | 2 | 2 | 1 | 1 | 15 | 15 | 25 | ND | D |
| I-10 | 2 | 2 | 1 | 2 | 0 | 0 | 0 | Del exon 1 | |
| I-11 | 10 | 1 | 1 | 2 | 5 | 50 | 15 | 2233 delT | |
| I-12 | 6 | 8 | 15 | 12 | 50 | 0 | 0 | A629P | |
| I-13 | 2 | 3 | 10 | 10 | 0 | 0 | 5 | G728D | |
| I-14 | 5 | 2 | 5 | 4 | 0 | 0 | 0 | ND | D |
| I-15 | 1 | 4 | 5 | 5 | 3 | 60 | 10 | Q724X | |
| I-16 | 2 | 2 | 1 | 1 | 0 | 10 | 25 | IVS21 AS -1, G>A | D |
| I-17 | 2 | 3 | 4 | 5 | 50 | 50 | 40 | IVS12 DS +1, g>a | D |
| I-1827 | 2 | 2 | 4 | 2 | 50 | 75 | 50 | G727R | D |
| I-19 | 1 | 4 | 5 | 3 | 5 | 5 | 5 | R201X | |
| I-20 | 4 | 1 | 2 | 1 | 10 | 5 | 0 | S487X | |
| I-21 | 2 | 1 | 1 | 2 | 25 | 15 | 25 | Q843X | D |
| I-22 | 1 | 4 | 4 | 4 | 0 | 0 | 0 | ND | |
| Mean | 2.455 | 2.409 | 3.364 | 3.227 | 11.273 | 15.455 | 11.136 | 11 of 22 | |
| SD | 2.154 | 1.652 | 3.499 | 2.943 | 17.097 | 23.192 | 14.551 | 50% | |
| Group II | |||||||||
| II-0112 | 12 | 15 | 15 | 10 | 5 | 0 | 10 | Q724H | |
| II-0217,30 | 5 | 4 | 6 | 7 | 0 | 0 | 5 | W1187X | D |
| II-0312 | 2 | 3 | 2 | 2 | 0 | 0 | 40 | Q724H | D |
| II-0426 | 36 | 36 | 36 | 36 | 0 | 0 | 60 | IVS8 AS dup5 | |
| II-0530 | 5 | 4 | 4 | 4 | 0 | 0 | 0 | IVS7 AS -1G>C | |
| II-0628 | 36 | 36 | 36 | 36 | 25 | 15 | 50 | R201X | |
| II-0730 | 13 | 15 | 24 | 20 | 50 | 10 | 75 | Q197X | |
| II-0819,30 | 4 | 4 | 4 | 5 | 0 | 0 | 0 | K1037N | D |
| II-0925 | 3 | 3 | 5 | 5 | 0 | 0 | 50 | Del exon 1 | D |
| II-1014 | 4 | 6 | 6 | 8 | 5 | 10 | 75 | 2757/8 delAG | D |
| II-1114 | 12 | 16 | 24 | 16 | 0 | 0 | 0 | G666R | |
| II-1214,30 | 7 | 11 | 13 | 8 | 50 | 5 | 50 | Del exon 7-19 | |
| II-1314 | 4 | 21 | 15 | 12 | 0 | 20 | 25 | Del exon 1 | |
| II-14 | 3 | 3 | 5 | 4 | 5 | 5 | 50 | IVS7 AS -1, G>C | |
| II-1514 | 36 | 36 | 36 | 33 | 40 | 25 | 40 | IVS9 DS +6 t>g | |
| II-1614 | 24 | 30 | 28 | 27 | 80 | 15 | 50 | 3936/7 delT | |
| II-1714 | 2 | 2 | 2 | 2 | 0 | 5 | 0 | 3061 del T | |
| II-1814 | 34 | 36 | 36 | 32 | 20 | 10 | 40 | G666R | |
| II-1921 | 3 | 2 | 4 | 3 | 0 | 5 | 0 | IVS11 SA -1, G>A | |
| II-2020 | 30 | 30 | 32 | 24 | 0 | 75 | 25 | ND | |
| II-2114 | 12 | 16 | 15 | 14 | 0 | 0 | 0 | del 4246-4260 | |
| II-2214 | 1 | 1 | 1 | 1 | 10 | 25 | 0 | Q1383X | D |
| II-2314 | 2 | 4 | 3 | 6 | 0 | 10 | 0 | 3061 del T | |
| II-2421,27 | 30 | 30 | 38 | 30 | 0 | 0 | 60 | G727R | |
| II-2514,30 | 2 | 4 | 3 | 4 | 25 | 10 | 0 | Del ex 20-23 | |
| II-2629,30 | 1 | 1 | 2 | 1 | 5 | 5 | 50 | Del ex 13-14 | D |
| II-2730 | 11 | 15 | 17 | 24 | 5 | 5 | 50 | IVS15 DS -1, G>A | D |
| II-28 | 24 | 28 | 34 | 30 | 50 | 5 | 90 | Del exon 1 | |
| II-2922 | 10 | 14 | 19 | 17 | 0 | 0 | 0 | L625X | D |
| II-3021 | 15 | 18 | 24 | 20 | 3 | 5 | 25 | Del ex 2-14 | |
| II-31 | 24 | 28 | 24 | 32 | 5 | 5 | 50 | 1020 dup5 | |
| II-3227 | 32 | 34 | 38 | 34 | 10 | 10 | 50 | G727R | |
| II-33 | 2 | 3 | 3 | 2 | 5 | 5 | 25 | ND | D |
| II-34 | 24 | 28 | 32 | 20 | 25 | 5 | 60 | Del 2-23 | |
| II-35 | 16 | 30 | 32 | 24 | 0 | 0 | 60 | Del exon 1 | |
| Mean | 13.743 | 16.200 | 17.657 | 15.800 | 12.086 | 8.286 | 33.286 | 10 of 35 | |
| SD | 12.200 | 12.762 | 13.482 | 12.034 | 19.589 | 13.501 | 27.060 | 28.6% | |
| P values: Group I v II | < 0.0001 | < 0.0001 | < 0.0001 | < 0.0001 | 0.8735 | 0.1453 | 0.0009 | ||
| Group III | |||||||||
| III-0123 | 27 | 32 | 35 | 31 | 15 | 75 | 50 | S833G | |
| III-02 | 10 | 15 | 12 | 20 | 0 | 10 | 0 | ND | |
| III-0323 | 10 | 6 | 6 | 12 | 0 | 0 | 5 | IVS21 DS +3, a>t | |
| Mean | 15.667 | 17.667 | 17.667 | 21.000 | 5.000 | 28.333 | 18.333 | 0 of 3 | |
| SD | 9.815 | 13.204 | 15.308 | 9.539 | 8.660 | 40.723 | 27.538 | 0% | |
Group I: Copper histidine treatment beginning after 1 month of age and onset of symptoms. Group II: Classic Menkes disease: Copper histidine treatment beginning within 1 month of age. Group III: Milder variants of Menkes disease: Copper histidine treatment beginning late after onset of (milder) symptoms. D=deceased; ND=not determined. Superscripts refer to previous reports (see References) in which the respective subjects were included.