Table 1 Clinical phenotype and genotype of NPC patients

1

F, AA^a

8 years

1st cousins

Hepatosplenomegaly at 6 months. Developmental delay at 2 years. Aggressive behavior, temper tantrums and sleep disturbances at 3 years. VSGP, ataxia, gelastic cataplexy, frequent falls, urinary and fecal incontinence at 5 years

Normal

p.G992W (G > T)

2

F, JA^a

4 years

1st cousins

Neonatal cholestatic jaundice. Hepatosplenomegaly at 2 weeks. Isolated splenomegaly at 1½ years. Developmental delay at 2 years

Not performed

3

M, MM^e

20 years

1st cousins

Neonatal cholestatic jaundice. Hepatosplenomegaly at 1 week. Ascites at 3 months. Low platelets at 5 years. VSGP at 11 years. Cognitive impairment, hyperactivity, poor concentration and aggressive behavior at 13 years. Ataxia at 15 years. Frequent falls, swallowing problems, speech problems, tonic–clonic seizure, absence seizure and gelastic cataplexy at 16 years

Normal

4

F, EA^e

4 years

1st cousins once removed

Neonatal cholestatic jaundice. Hepatosplenomegaly at 2 weeks

Not performed

5

F, DA^e

2 years

1st cousins

Neonatal cholestatic jaundice. Hepatosplenomegaly at 1 month

Not performed

6

M, AS^b

2 years

1st cousins

Neonatal cholestatic jaundice. Hepatosplenomegaly and central hypotonia at 3 months. Mild speech delay, normal cognition, behavior and gait at 2 years

Not performed

7

M, MS^b

6 years

1st cousins

Neonatal cholestatic jaundice. Hepatosplenomegaly, ascites and thrombocytopenia at 3 months. Central hypotonia and swallowing problems at 1 year. Sleep disturbance at 3 years. Ataxia at 4 years

Not performed

8

M, YS^c

9 years

1st cousins

Splenomegaly at 3 years. Developmental delay at 2 years. Gelastic cataplexy, cognitive impairment, hyperactivity and poor attention at 4 years. Urinary and fecal incontinence at 5 years. VSGP, speech problem and swallowing problems at 6 years. Ataxia, frequent falls, spasticity and tonic–clonic seizure at 6.5 years

Increased signal intensity on T2-weighted images in the cerebral white matter

9

M, AS^c

12 years

1st cousins

Hepatosplenomegaly at 3 years. VSGP, frequent falls and developmental delay at 2½ years. Ataxia at 3½ years. Speech problem and swallowing problems at 4 years. Spasticity at 4½ years. Gelastic cataplexy and cognitive impairment at 5 years. Absence seizure at 10½ years

Not performed

10

M, MS^c

7 years^f

1st cousins

Hepatosplenomegaly at 2 years. VSGP, spasticity and inability to walk at 4 years. Speech and swallowing problems, gelastic cataplexy, urinary and fecal incontinence at 5 years. Tonic-clonic seizure and cognitive impairment at 6 years

Not performed

11

F, SY^d

14 years

1st cousins

Splenomegaly and VSGP at 5 years. Ataxia at 6 years

Normal

12

F, SA^a

13 years

1st cousins

Splenomegaly, VSGP, ataxia, speech and swallowing problems, absence seizure, cognitive impairment and sleep disturbance at 5 years. Gelastic cataplexy at 7 years

Normal

13

F, RS^b

7½

1st cousins

Hepatosplenomegaly at 1 year. Frequent falls at 3 years. VSGP, ataxia, swallowing and speech problems, gelastic cataplexy, cognitive impairment, poor school performance, aggressive behavior and sleep disturbances at 4 years

Not performed

14

F, GY^d

26 years^f

1st cousins

Ataxia at 15 years. VSGP and cognitive impairment and abnormal behavior at 20 years. Spasticity at 21 years. Speech problem and swallowing problems at 22 years. Frequent falls at 23 years. Urinary incontinence at 24 years

Not performed

15

F, IZ

31 years

2nd cousins

Ataxia at 19 years. VSGP and spasticity at 21 years. Splenomegaly, Speech and swallowing problems at 24 years. Urinary and fecal incontinence at 27 years. Cognitive impairment and abnormal behavior at 28 years

Atrophic changes in the cerebellar hemisphere

A927V (C > T)

16

M, KH

2 years

1st cousins

Cholestatic jaundice. Hepatosplenomegaly at 3 months. Hypotonia and motor delay at 1 year. Thrombocytopenia at 1 year

Normal

p.V845Cfs*24

(Novel)