Suppl. Table 4a. Movement disorder (“Early diagnosis” versus selective metabolic investigation group)
Disease / Mode of diagnosis / Totaln / No MD
n (%) / MD
n (%) / OR from logistic regression† with covariate age*
ASS-D / NBS, HRF-neo, Prenatal / 10 / 10 (100) / 0 (0) / MoD: ORu=5.73, 95%CI [0.66;753.83], p=0.133
LR (df=1)=0.69, p=0.407
Selective / 62 / 49 (79) / 13 (21)
ASL-D / NBS, HRF-neo, Prenatal / 9 / 8 (89) / 1 (11) / MoD: ORu=2.78, 95%CI [0.53;28.17], p=0.245
LR (df=1)=0.01, p=0.918
Selective / 37 / 25 (68) / 12 (32)
ARG1-D / NBS, HRF-neo, Prenatal / 4 / 4 (100) / 0 (0) / MoD: ORu=11.57, 95%CI [0.78;1741.93], p=0.078
LR (df=1)=0.31, p=0.580
Selective / 7 / 3 (43) / 4 (57)
The group “early diagnosis” included patients identified by newborn screening (NBS), prenatal testing or high-risk family screening of asymptomatic newborns (HRF-neo). Cases with a value for the covariate age were included; †according to Firth's bias reduced logistic regression approach with penalized profile likelihood based confidence intervals for parameter estimates (Heinze et al. 2002; Heinze et al. 2013);*age at first time of MD for those with MD and age at last regular visit for those without MD; CI, confidence interval; D, deficiency; LR, penalized likelihood ratio test for comparison of nested models (Heinze et al. 2013); MD, movement disorder; MoD, mode of diagnosis; OR, odds ratio (reference group: NBS+HRF-neo+Prenatal, reference category: no MD); ORu, unadjusted OR (if LR was not significant); Prenatal, prenatal testing; Selective, selective metabolic investigation. Age distribution is specified in Suppl. Table 4c.
Suppl. Table 4b. Distribution of age at first time of movement disorder or at last regular visit respectively by disease and mode of diagnosis
Disease / Mode of diagnosis / Total n / AgeMean; median (n)
(Q1;Q3)
[min;max] in years
No movement disorder* / Movement disorder**
ASS-D / NBS / 6 / 2.19; 1.19 (6)
(0.93;3.31)
[0.87;5.00] / n.d.
Selective / 62 / 10.07; 7.56 (49)
(4.24;14.19)
[0.13;34.77] / 7.98; 8.31 (13)
(3.85;11.34)
[0.98;15.35]
ASL-D / NBS / 8 / 6.70; 6.74 (7)
(5.02;7.57)
[1.85;13.09] / 12.01; 12.01 (1)
(12.01;12.01)
[12.01;12.01]
Selective / 37 / 10.92; 8.98 (25)
(5.41;13.48)
[0.30;39.43] / 9.73; 8.09 (12)
(5.29;13.79)
[0.15;26.39]
ARG1-D / NBS / 4 / 3.02; 2.19 (4)
(1.85;3.36)
[1.10;6.60] / n.d.
Selective / 7 / 15.30; 8.11 (3)
(7.92;19.09)
[7.73;30.07] / 19.56; 20.49 (4)
(16.53;23.52)
[9.82;27.43]
Data are shown as mean; median (Q1;Q3) [min;max]; *age at last regular visit; **age at first time of movement disorder; D, deficiency;NBS, newborn screening; Selective, selective metabolic investigation.
Suppl. Table 4c. Distribution of age at first time of movement disorder or at last regular visit respectively by disease and mode of diagnosis
Disease / Mode of diagnosis / Total n / AgeMean; median (n)
(Q1;Q3)
[min;max] in years
No movement disorder* / Movement disorder**
ASS-D / NBS, HRF-neo, Prenatal / 10 / 4.37; 4.15 (10)
(1.14;5.14)
[0.87;10.66] / n.d.
Selective / 62 / 10.07; 7.56 (49)
(4.24;14.19) [0.13;34.77] / 7.98; 8.31 (13)
(3.85;11.34) [0.98;15.35]
ASL-D / NBS, HRF-neo, Prenatal / 9 / 6.32; 6.03 (8)
(4.46;7.50)
[1.85;13.09] / 12.01; 12.01 (1)
(12.01;12.01)
[12.01;12.01]
Selective / 37 / 10.92; 8.98 (25)
(5.41;13.48)
[0.30;39.43] / 9.73; 8.09 (12)
(5.29;13.79)
[0.15;26.39]
ARG1-D / NBS, HRF-neo, Prenatal / 4 / 3.02; 2.19 (4)
(1.85;3.36)
[1.10;6.60] / n.d.
Selective / 7 / 15.30; 8.11 (3)
(7.92;19.09)
[7.73;30.07] / 19.56; 20.49 (4)
(16.53;23.52)
[9.82;27.43]
Data are shown as mean; median (Q1;Q3) [min;max]; *age at last regular visit; **age at first time of movement disorder; D, deficiency;HRF-neo, high-risk family screening of asymptomatic newborns; NBS, newborn screening; Prenatal, prenatal testing; Selective, selective metabolic investigation.
Suppl. Table 4d. Delayed milestones (“Early diagnosis” versus selective metabolic investigation group)
Disease / Mode of diagnosis / Totaln / No DM
n (%) / DM
n (%) / OR from logistic regression† with covariate age*
ASS-D / NBS, HRF-neo, Prenatal / 10 / 7 (73) / 3 (27) / MoD: ORu=0.45, 95%CI [0.11;2.12], p=0.296
LR (df=1)=0.71, p=0.400
Selective / 59 / 49 (83) / 10 (17)
ASL-D / NBS, HRF-neo, Prenatal / 9 / 8 (89) / 1 (11) / MoD: ORu=0.93, 95%CI [0.14;10.18], p=0.941
LR (df=1)=0.02, p=0.893
Selective / 31 / 27 (87) / 4 (13)
ARG1-D / NBS, HRF-neo, Prenatal / 4 / 4 (100) / 0 (0) / MoD: ORa=0.43, 95%CI [<0.01;126.28], p=0.736
LR (df=1)=5.36, p=0.021
Selective / 7 / 3 (43) / 4 (57)
Only cases with a value for the covariate age were included; †according to Firth's bias reduced logistic regression approach with penalized profile likelihood based confidence intervals for parameter estimates (Heinze et al. 2002; Heinze et al. 2013);*age at last regular visit; CI, confidence interval; D, deficiency;DM, delayed milestones; HRF-neo, high-risk family screening of asymptomatic newborns; LR, penalized likelihood ratio test for comparison of nested models (Heinze et al. 2013); MoD, mode of diagnosis; NBS, newborn screening; OR, odds ratio (reference group: NBS, reference category: no delayed milestones); ORa, adjusted OR (if LR was significant); ORu, unadjusted OR (if LR was not significant); Prenatal, prenatal testing; Selective, selective metabolic investigation. Age distribution is specified in Suppl. Table 4f.
Suppl. Table 4e. Distribution of age at last regular visit for those with or without delayed milestones by disease and mode of diagnosis
Disease / Mode of diagnosis / Total n / Age*Mean; median
(Q1;Q3)
[min;max] in years
ASS-D / NBS / 6 / 2.19; 1.19
(0.93;3.31)
[0.87;5.00]
Selective / 59 / 9.66; 8.31
(4.19;13.67)
[0.13;34.77]
ASL-D / NBS / 8 / 6.65; 5.96
(4.09;8.56)
[1.85;13.09]
Selective / 31 / 11.06; 9.19
(6.11;13.74)
[0.30;39.43]
ARG1-D / NBS / 4 / 3.02; 2.19
(1.85;3.36)
[1.10;6.60]
Selective / 7 / 17.72; 18.77
(8.92;24.82)
[7.73;30.07]
Data are shown as mean; median (Q1;Q3) [min;max]; *Age at last regular visit; D, deficiency;HRF-neo, high-risk family screening of asymptomatic newborns; NBS, newborn screening; Selective, selective metabolic investigation.
Suppl. Table 4f. Distribution of age at last regular visit for those with or without delayed milestones by disease and mode of diagnosis
Disease / Mode of diagnosis / Total n / Age*Mean; median
(Q1;Q3)
[min;max] in years
ASS-D / NBS, HRF-neo, Prenatal / 10 / 4.37; 4.15
(1.14;5.14)
[0.87;10.66]
Selective / 59 / 9.66; 8.31
(4.19;13.67)
[0.13;34.77]
ASL-D / NBS, HRF-neo, Prenatal / 9 / 6.32; 5.33
(3.68;7.41)
[1.85;13.09]
Selective / 31 / 11.06; 9.19
(6.11;13.74)
[0.30;39.43]
ARG1-D / NBS, HRF-neo, Prenatal / 4 / 3.02; 2.19
(1.85;3.36)
[1.10;6.60]
Selective / 7 / 17.72; 18.77
(8.92;24.82)
[7.73;30.07]
Data are shown as mean; median (Q1;Q3) [min;max]; *age at last regular visit; D, deficiency;HRF-neo, high-risk family screening of asymptomatic newborns; NBS, newborn screening; Prenatal, prenatal testing; Selective, selective metabolic investigation.