Table 1 Case profiles
Case 1 | Case 2 | Case 3 | |
|---|---|---|---|
Age at onset (years) | 11 | 27 | 22 |
Initial symptom | Intellectual disability | Painful dystonia | Schizophrenia |
Age at diagnosis (years) | 25 | 28 | 35 |
Visceral signs | |||
Splenomegaly | Mild | Mild | Mild |
Neonatal jaundice | + | None | None |
Neurological signs | |||
VSGP | + | None | None |
Dysphagia | + | None | None |
Spastic ataxia | + | None | None |
IVM | Chorea, athetosis, dystonia, myoclonus | Dystonia | None |
Psychiatric signs | |||
Cognitive decline | + | None | None |
Psychotic symptoms | + | + | + |
NPC-SI a | |||
Percentile | 98% | 18% | 32% |
RPS | 183 | 47 | 67 |
Filipin pattern | Variant | Variant | Variant |
ASM activity | 221 | 213 | 165 |
(nmol/mg protein/h) | 99% of control | 95% of control | 73% of control |
Phenotype (cDx) | Juvenile | Adult | Adult |
NPC1 gene mutations | |||
Father | c.1421C > T | c.3011C > T | c.3011C > T |
(p.P474L) | (p.S1004 L) | (p.S1004 L) | |
Mother | c.3722 T > C | c.160_161insG | c.160_161insG |
(p.L1241S) | (p.D54GfsX4) | (p.D54GfsX4) | |
Brain MRI | Sl. atrophic | Normal | Sl. atrophic |
Hypoperfusion on ECD-SPECT | Frontal | Frontal | Frontal |
CSF Analysis | |||
p-Tau (< 55) | 59 pg/mL | 47 pg/mL | 36 pg/mL |
h-Tau (< 300) | 371 pg/mL | 214 pg/mL | 188 pg/mL |
Cupper | |||
Serum Cu (> 68) | 76 μg/dL | 82 μg/dL | 88 μg/dL |
Serum Cp (> 21) | 22 mg/dL | 18 mg/dL | 22 mg/dL |
Urine Cu (> 20) | NA | NA | 32 μg/day |
Urine bile acid b | |||
SNAG-Δ5-CT (< 11) | NA | 13 ng/mL | 92 ng/mL |
SNAG-Δ5-CA (< 282) | NA | 42 ng/mL | 317 ng/mL |
SNAG-Δ5-CG (< 258) | NA | 69 ng/mL | 481 ng/mL |