Table 1.
NPC1 patient demographics.
| Age of onset (years) | Age of first neurological symptom (years) | Age-adjusted neurological severity score | LysoTracker levels (fold change) | Presenting symptom | First neurological symptom | Sex | Pathogenic DNA variants | Predicted protein changes |
|---|---|---|---|---|---|---|---|---|
| N/A | N/A | 0.1 | 9.7 | None | None reported | M* | c.410C>T, c.2000C>T | p.T137M, p.S667L |
| − 0.4** | N/A | 0.0 | 43.1 | Hyperecholic intestines, IUGR | None reported | F | c.3182T>C, c.1628C>T | p.I1061T, p.P543L |
| 0 | N/A | 2.0 | 30.9 | Splenomegaly | None reported | M | c.3182T>C, c.3182T>C | p.I1061T, p.I1061T |
| 0 | N/A | 0.0 | 38.3 | Jaundice, liver failure† | None reported | M | c.3182T>C, c.681T>G | p.I1061T, p.C227W |
| 0.1 | N/A | 2.4 | 36.7 | Jaundice | None reported | M | c.3182T>C, c.3107C>T | p.I1061T, p.T1036M |
| 0.5 | N/A | 0.1 | 9.9 | Splenomegaly | None reported | F | c.2932C>T, c.3246-2A>G | p.R978C, (predicted abnormal splicing) |
| 1 | N/A | 0.1 | 7.1 | Hepatosplenomegaly | None reported | F* | c.665A>G, c.1402T>G | p.N222S, p.C468G |
| 2 | N/A | 0.1 | 7.8 | Splenomegaly | None reported | F* | c.665A>G, c.1402T>G | p.N222S, p.C468G |
| − 0.4** | 1.2 | 0.8 | 24.1 | Fetal ascites | Not walking at 14 months | F | c.3182T>C, c.3182T>C | p.I1061T, p.I1061T |
| 0 | 1 | 8.0 | 66.6 | Jaundice | Developmental plateau | M | c.3565_3566insG, 2008_2011delTGCT | p.E1189Gfs*69, p.C670Pfs*12 |
| 0 | 1.5 | 5.1 | 47.9 | Hepatosplenomegaly | Loss of gross motor skills, dysphagia | M | c.2978delG, c.3591+4delA | p.G993Efs*4, (possible splicing effect) |
| 0 | 3 | 2.2 | 17.9 | Jaundice, splenomegaly | Clumsy, dysarthria | M | c.3182T>C, c.3182T>C | p.I1061T, p.I1061T |
| 0 | 3.5 | 2.0 | 16.0 | Hepatosplenomegaly, jaundice | Vertical gaze palsy | M | c.3182T>C, c.3182T>C | p.I1061T, p.I1061T |
| 0 | 8 | 1.2 | 12.2 | Splenomegaly | Learning disability, fine motor ataxia | F* | c.3107C>T, c.2861C>T | p.T1036M, p.S954L |
| 0.01 | 7 | 2.0 | 32.9 | Jaundice | Vertical gaze palsy | M | c.3182T>C, c.3281T>C | p.I1061T, p.I1094T |
| 0.3 | 2 | 1.3 | 44.1 | Hepatosplenomegaly | Clumsiness, speech delay | M | c.3439G>T, c.3742_3745delCTCA | p.G1146V, p.L1248Vfs*3 |
| 0.5 | 1.5 | 4.5 | 68.0 | Splenomegaly | Gross motor delay | M | c.2516T>G, c.3259T>C | p.I839R, p.F1087L |
| 0.7 | 2 | 2.5 | 29.5 | Splenomegaly | Clumsiness, possibly vertical gaze palsy | F | c.3493G>A, c.3741_3744delACTC | p.V1165M, p.L1248Vfs*3 |
| 1 | 3 | 1.4 | 38.4 | Splenomegaly | Fine motor limitation | M | c.3182T>C, c.3556C>G | p.I1061T, p.R1186G |
| 1.7 | 1.7 | 6.7 | 26.9 | Developmental delay | Gross motor delay, speech delay | F | c.57+1G>T, Unknown | (possible splicing effect), Unknown |
| 2 | 2 | 1.0 | 20.9 | Splenomegaly | Clumsiness | F* | c.1920delG, c.1554—1009G>A | p.H641Tfs*2, (predicted abnormal splicing) |
| 2 | 2 | 1.7 | 19.8 | Splenomegaly | Clumsiness | F* | c.1920delG, c.1554—1009G>A | p.H641Tfs*2, (predicted abnormal splicing) |
| 3 | 3 | 6.7 | 55.7 | Fine motor ataxia | Abnormal gait, fine motor skills | F | c.2979dupA, c.2103C>G | p.D994Rfs*13, p.N701K |
| 3 | 3 | 1.5 | 10.5 | Learning disability | Learning disability | F* | c.410C>T, c.2000C>T | p.T137M, p.S667L |
| 3 | 9 | 1.3 | 10.5 | Splenomegaly | Learning disability | M* | c.3107C>T, c.2861C>T | p.T1036M, p.S954L |
| 4 | 5 | 0.9 | 20.4 | Hepatosplenomegaly | School difficulties | F | c.3182T>C, c.3019C>G or C>T | p.I1061T, p.F1167C |
| 5 | 5 | 1.7 | 21.6 | Vertical gaze palsy | Vertical gaze palsy | F | c.3182T>C, c.3182T>C | p.I1061T, p.I1061T |
| 5 | 5 | 2.0 | 13.5 | Developmental delay | Vertical gaze palsy | F | c.2201G>T, c.2201G>T | p.S734I, p.S734I |
| 5 | 10 | 0.8 | 22.0 | Hepatosplenomegaly | Clumsiness, hearing loss | F | c.2474A>G, c.289_291dupTGT | p.Y825C, p.C97_P98insC |
| 6 | 6 | 1.2 | 13.3 | Learning disability | Learning disability | M | c.2861C>T, Unknown | p.S954L, Unknown |
| 6 | 6 | 2.2 | 8.1 | Seizures | Seizures | M | c.1211G>A, c.3019C>G | p.R404Q, p.P1007A |
| 7 | 7 | 0.8 | 9.8 | Clumsiness | Clumsiness | F* | c.1552C>T, c.2594C>T | p.R518W, p.S865L |
| 7 | 7 | 1.3 | 10.4 | Learning disability | Learning disability | F* | c.1552C>T, c.2594C>T | p.R518W, p.S865L |
| 8 | 8 | 1.2 | 28.3 | Learning delay | Learning delay, hearing loss | M | 6 poss. cDNA changes, c.3662delT | p.F842L, p.F1221Sfs*21 |
| 8 | 8 | 1.4 | 6.5 | Learning disability | Learning disability | F | c.3182T>C, c.3019C>G or C>T | p.I1061T, p.P1007A |
| 10 | 10 | 1.0 | 8.5 | Learning delay | Clumsiness, learning disability | F | c.1211G>A, c.2861C>T, c.1123A>G | p.R404Q, p.S954L, p.T375A |
| 11 | 11 | 0.9 | 11.2 | Learning disability | Learning disability | F | c.3182T>C, c.743G>T | p.I1061T, p.G248V |
| 12 | 12 | 0.6 | 13.9 | Unsteady gait | Abnormal gait | M | c.743 G>T, c.3410_3411insA | p.G248V, p.N1137Kfs*121 |
| 17 | 17 | 0.9 | 4.8 | Clumsiness | Clumsiness | M | c.3019C>G or C>T, Unknown | p.P1007A, Unknown |
| 18 | 18 | 0.7 | 20.8 | Psychosis | Psychosis | F | c.3176G>A, c.3742_3745delCTCA | p.R1059Q, p.L1248Vfs*3 |
| 18 | 18 | 0.6 | 8.0 | Depression | Psychiatric symptoms | F | c.3182T>C, c.2861C>T | p.I1061T, p.S954L |
*Part of a sibling pair.
**Negative values indicates age of onset in utero.
†Subsequently received a liver transplant.