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Table 1 Individual chronic visceral ASMD patients' characteristics

From: Chronic visceral acid sphingomyelinase deficiency (Niemann-Pick disease type B) in 16 Polish patients: long-term follow-up

Pt Sex Ancestry First signs and symptoms + age Age at diagnosis *Acid sphingomyelinase activity in leukocytes (L), skin fibroblasts (F) or dried blood spot (B); % of residual activity **Chitotriosidase activity (age at measurement) ***SPC and SPC-509 measurement in plasma; Age at measurement Molecular variant/protein effect Natural history – the last follow-up data Outcome, current age
1 M
Gypsy
6 mo
mild HS, cholestatic jaundice (TB 6.5, DB 3.0), elevated ST (AST 112, ALT 39), coagulopathy (INR 1.8), lipid serum profile – nk
1 y 3.9 nmol/mg protein/18 h (L);
5.6%
40 (1 y) n.a. c.1177 T > G, p.Trp393Gly/
c.1177 T > G, p.Trp393Gly
mild HS, thrombocytopenia (PLT 14), elevated ST (AST 160, ALT 60), cholestasis (TB 10.6, DB 6.5), coagulopathy (INR 2.8), hypoalbuminemia, ascites, interstitial lung disease on chest X-ray and CT, lipid serum profile – nk, cherry red spot, death due to Neisseria meningitidis sepsis, in liver biopsy post-mortem cirrhosis hepatis Died at 1.5 y
2 F
Gypsy
7 mo
mild HS, cholestatic jaundice (TB 4.9, DB 3.5), elevated ST (AST 200, ALT 80), coagulopathy (INR 1.6), lipid serum profile – nk
1 mo – family screening 12.0 nmol/mg protein/18 h (L);
17.2%
n.a. n.a. c.1177 T > G, p.Trp393Gly/c.1177 T > G, p.Trp393Gly sinus node dysfunction and permanent pacemaker implantation at 1y;
mild HS, thrombocytopenia (PLT 84), elevated ST (AST 1110, ALT 40), cholestasis (TB 12.3, DB 8.5), coagulopathy (INR 2.74), hypoalbuminemia, interstitial lung disease on chest X-ray, lipid serum profile – nk, cherry red spot, death due to heart failure
Died at 3 y
3 M
Gypsy
3 y
mild HS, elevated ST (AST 100, ALT 80), normal lipid serum profile, normal spirometry
2 mo – family screening 0 nmol/mg protein/18 h (L);
0%
41 (2 mo);
296 (5 y)
785
4364;
9.5 y
c.1177 T > G, p.Trp393Gly/c.1177 T > G, p.Trp393Gly mild HS, elevated ST (AST 80, ALT 75), no cholestasis, normal coagulation profile, interstitial lung disease on chest X-ray, normal lipid serum profile, normal stature, normal neurologic examination, normal spirometry 9.5 y
4 F
Gypsy
6 mo
mild HS, elevated ST (AST 470, ALT 370), lipid serum profile: TC 186, LDL-C 104, HDL-C 9, TG 365)
6 mo – family screening 0.01 nmol/mg protein/18 h (L);
0.01%
488 (2.5 y) 26.8#
25.6#;
2.5 y
c.1177 T > G, p.Trp393Gly/c.1177 T > G, p.Trp393Gly mild HS, elevated ST (AST 170, ALT 150), no cholestasis, lipid serum profile: TC 264, LDL-C 205, HDL-C 18, TG 206, cherry red spot, normal stature, autism spectrum disorders 2.5 y
5 M
Gypsy
6 mo
mild HS, elevated ST (AST 160 ALT 130), lipid serum profile: TC 184, LDL-C 54, HDL-C 20, TG 548
6 mo – family screening n.a. n.a. n.a. c.1177 T > G, p.Trp393Gly/
c.1177 T > G, p.Trp393Gly
mild HS, elevated ST (AST 100, ALT 90), no cholestasis, normal lipid serum profile, cherry red spot, normal neurological examination 1 y
6 F
Polish
2.5 y
mild HS, elevated ST (AST 140, ALT 65), lipid serum profile: TC 298, LDL-C 224, HDL-C 14, TG 299
12 y 14 nmol/mg protein/18 h (L);
20%
1220 (12 y), 1600 (14 y) 274
13,670;
21 y
c.496G > A, p.Gly166Arg/
3′ acceptor splice site mutation (g2610c)
moderate HS, elevated ST (AST 155, ALT 90), lipid serum profile: TC 290, LDL-C 229, HDL-C 18, TG 321, no cherry red spot, short stature, spirometry - nk 21 y
7 M
Polish
1.5 y
mild HS, normal ST, normal lipid serum profile
2 y 0.71 nmol/mg protein/18 h (L);
1%
3720 (2 y);
3300 (9 y); 3700 (14 y); 4190 (16 y)
n.a. c.496G > A, p.Gly166Arg/ c.496G > A, p.Gly166Arg moderate HS, normal ST, normal lipid serum profile, cherry red spot, interstitial lung disease on chest X-ray, hearing loss, normal stature, normal spirometry 18 y
8 M
Polish
Splenectomy at 5 y, normal ST, normal lipid serum profile 12 y 22 nmol/mg protein/18 h (L);
31%
1 (12 y)
Chitotriosidase deficiency - homozygote for a 24 bp duplication in the CHIT1 gene
36
47;
18 y
c.866G > A, p.Arg289His/
c.496G > A, p.Gly166Arg
No hepatomegaly, normal ST, normal lipid serum profile, no cherry red spot, normal stature, spirometry - nk 18 y
9 M
Polish
mild HS and thrombocytopenia (PLT 100–120) noted from years, lipid serum profile: TC 120, LDL-C 56, HDL-C 34, TG 155, normal spiormetry 50 y 112 pmol/spot/20 h (B);
56%
(2nd measurement –
111 pmol/spot/20 h)
72 (50 y);
45 (54 y)
49
689;
54 y
c.107 T > C (p.V36A; rs1050228)/ c.107 T > C (p.V36A; rs1050228) mild HS, thrombocytopenia (PLT 85), normal ST, lipid serum profile: TC 272, LDL-C 201, HDL-C 33, TG 191, no cherry red spot, normal spirometry 54 y
10 M
Polish
Splenectomy at 48 y, normal ST, lipid serum profile: TC 140, LDL-C 82, HDL-C 27, TG 155, normal spirometry 49 y 11 nmol/mg protein/18 h (L),
15.7%
68 (49 y);
53 (51 y)
143
535;
60 y
c.940G > A, p.Val314Met/
c.940G > A, p.Val314Met
No hepatomegaly, normal ST, lipid serum profile: TC 112, LDL-C 41, HDL-C 39, TG 157,, no cherry red spot, normal spirometry 60 y
11 M
Polish
1 y
mild HS, normal PLT, lipid serum profile: TC 195, LDL-C 142, HDL-C 21, TG 164
45 y 1.5 ukat/kg protein (F);
5%
569 (45 y);
232 (60 y)
589
7035;
60 y
c.1400A > C, p.Tyr467Ser/
c.996delC, p.F333Sfs*52
mild HS, thrombocytopenia (PLT 110), normal ST, lipid serum profile: TC 256, LDL-C 197, HDL-C 18, TG 256, interstitial lung disease on chest X-ray and CT, deteriorating spirometry analyses: FEV1–3.44, VC max – 4.09, FEV1%VCmax – 84 (45 y), FEV1–3.37, VC max – 4.15, FEV1%VCmax – 78 (60 y), no cherry red spot, 60 y
12 F
Polish
6 mo
mild HS, normal ST, lipid serum profile: TC 140, LDL-C 98, HDL-C 18, TG 120
4 y 0.15 ukat/kg protein (F);
0.5%
908 (20 y) 529
5015;
40 y
c.1823_1825delGCC, p.delR610/ c.575delC, p.P192fsX62 mild HS, normal ST, cherry red spot, interstitial lung disease on chest X-ray and CT, deteriorating spirometry analyses lipid serum profile: TC 240, LDL-C 180, HDL-C 20, TG 220; deteriorating spirometry: FEV1–3.04, VC max – 3.09, FEV1%VCmax – 64 (20 y), FEV1–3.04, VC max – 3.11, FEV1%VCmax – 58 (40 y) 40 y
13 F
Polish
10 y
mild HS, normal ST, normal lipid serum profile
12 y 0 ukat/kg protein (F);
0%
171 (12 y);
200 (13 y)
n.a. c.496G > A, p.Gly166Arg/c.496G > A, p.Gly166Arg mild HS, normal ST, normal lipid serum profile, no cherry red spot, normal stature, spirometry - nk 17 y
14 F
Polish
5 y
massive HS, normal ST, normal lipid serum profile
14 y 0 ukat/kg protein (F);
0%
2140 (14 y) n.a. c.496G > A, p.Gly166Arg/c.496G > A, p.Gly166Arg massive HS, normal ST, normal lipid serum profile, no cherry red spot, normal stature, spirometry - nk 21 y
15 M
Polish
4 y
mild HS, normal ST, normal lipid serum profile
10 y n.a. 301 (10 y);
206 (15 y)
182
1256;
20 y
c.491G > T, p.Gly164Val/c.996delC, p.F333Sfs*52 mild HS, normal ST, normal lipid serum profile, no cherry red spot, normal stature, spirometry - nk 20 y
16 F
Polish
mild S, normal ST, normal lipid serum profile 33 y 7 nmol/mg protein/18 h (L);10% 168 (33 y);
158 (34 y)
n.a. c.996delC, p.F333Sfs*52/c.1142C > T, p.Ser381Phe mild splenomegaly, normal ST, normal lipid serum profile, no cherry red spot, spirometry - nk 42 y
  1. M Male; F Female; SPC Lysosphingomyelin; HS Hepatosplenomegaly; n.a. Not analyzed; ST Serum transaminases; AST Aspartate aminotransferase, ALT Alanine aminotransferase, INR International TG Triglycerides; TC Total cholesterol; LDL-C Low-density lipoprotein-cholesterol; HDL-C High-density lipoprotein-cholesterol; nk not known; mo Months; y years;
  2. Reference values: ALT, < 18 months, < 55/60 U/L; 18 months–12 years, boys, < 40 U/L, girls, < 35 U/L; > 12 years, boys, < 26 U/L, girls, < 22 U/L; AST, < 52 U/L; total serum bilirubin, < 1.0 mg/dl; total cholesterol, < 170 mg/dl; LDL-C, < 110 mg/dl; HDL-C, > 45 mg/dl; TG, 1–9 years, < 75 mg/dl, 10–19 years, < 90 mg/dl; PLT, 150–450 K/μL
  3. *Reference range for acid sphingomyelinase activity in leukocytes: 70-108 nmol/mg protein/18hr; skin fibroblasts 30 ± 10 ukat/kg protein; dried blood spot: 200-3500 pmol/spot/hr.
  4. **Reference range for chitotriosidase activity in plasma: < 150 nmol/ml/hr.
  5. ***Reference range for SPC:4-55 nmol/l, SPC-509: 18-69 nmol/l.
  6. #Reference range for SPC: 0.2-15, SPC-509: 0.15-3.7