Table 2.
Biochemical and molecular profile of patients with reduced biotinidase activity (n = 38)
| Patient | Gender | Allele 1 | Allele 2 | Expected type of BD according to genotype | Type of BD according to enzyme activity b | Biotinidase activity a | Manner of diagnosis |
|---|---|---|---|---|---|---|---|
| 01 |
F |
c.643C > T (p.L215F) |
c.755A > G (p.D252G) |
Profound |
N/A |
21.88 U |
NS |
| 02c |
M |
c.755A > G (p.D252G) |
c.755A > G (p.D252G) |
Profound |
Profound |
0.1; 0.4; 0.33; 0.44; 0.16; 0.32 |
S |
| 03 |
F |
c.1612C > T (p.R538C) |
c.1612C > T (p.R538C) |
Profound |
Profound |
0.12 |
S |
| 04 |
M |
c.1330G > C (p.D444H) |
c.98_104del7ins3 |
Partial |
Partial |
1.5 |
NS |
| 05 |
F |
c.1330G > C (p.D444H) |
c.[470G > A;1330G > C] (p.[R157H;D444H]) |
Partial |
Partial |
1.8 |
NS |
| 06 |
M |
c.1330G > C (p.D444H) |
c.[511G > A;1330G > C] (p.[A171T;D444H]) |
Partial |
Partial |
1.4 |
NS |
| 07 |
F |
c.1330G > C (p.D444H) |
c.[511G > A;1330G > C] (p.[A171T;D444H]) |
Partial |
Hz |
2.5 |
NS |
| 08 |
F |
c.1330G > C (p.D444H) |
c.[511G > A;1330G > C] (p.[A171T;D444H]) |
Partial |
N/A |
45.81 U |
NS |
| 09 |
F |
c.1330G > C (p.D444H) |
c.594_596delCGT (p.V199del) |
Partial |
Partial |
1.2; 1.9 |
NS |
| 10 |
F |
c.1330G > C (p.D444H) |
c.[595G > A;1413 T > C] (p.[V199M;C471C]) |
Partial |
Hz |
2.8 |
NS |
| 11 |
M |
c.1330G > C (p.D444H) |
c.755A > G (p.D252G) |
Partial |
Partial |
1.7 |
NS |
| 12 |
F |
c.1330G > C (p.D444H) |
c.755A > G (p.D252G) |
Partial |
Partial |
1.2 |
NS |
| 13 |
F |
c.1330G > C (p.D444H) |
c.755A > G (p.D252G) |
Partial |
Hz |
2.4 |
NS |
| 14 |
M |
c.1330G > C (p.D444H) |
c.755A > G (p.D252G) |
Partial |
N/A |
51.37 U |
NS |
| 15 |
M |
c.1330G > C (p.D444H) |
c.933delT |
Partial |
Partial |
1.6 |
NS |
| 16 |
F |
c.1330G > C (p.D444H)d |
c.100G > Ad |
Partial or Hz |
Partial |
1.2; 2.04 |
NS |
| 17 |
M |
c.1330G > C (p.D444H)d |
c.643C > T (p.L215F)d |
Partial or Hz |
Hz |
2.4 |
NS |
| 18 |
F |
c.1330G > C (p.D444H)d |
c.1629C > A (p.D543E)d |
Partial or Hz |
Hz |
2.6 |
NS |
| 19 |
M |
c.1413 T > C (p.C471C) |
c.[511G > A;1330G > C] (p.[A171T;D444H]) |
Hz |
Hz |
3.3 |
NS |
| 20 |
M |
c.1595C > T (p.T532M) |
N |
Hz |
Hz |
1.5; 2.9; 4.4 |
NS |
| 21 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
Hz |
0.7; 3.3 |
NS |
| 22 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
Hz |
3.7 |
NS |
| 23 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
Hz |
2.8; 2.7 |
NS |
| 24 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
48.75 U |
NS |
| 25 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
51.83 U |
NS |
| 26 |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
46.88 U |
NS |
| 27c |
M |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
52.73 U |
NS |
| 28 |
F |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
40.94 U |
NS |
| 29 |
F |
c.1330G > C (p.D444H) |
c.1330G > C (p.D444H) |
≈ Hz |
N/A |
45.37 U |
NS |
| 30 |
M |
c.1330G > C(p.D444H) |
N |
≈ N |
Borderline (Hz/N) |
4.9 |
NS |
| 31 |
F |
c.1330G > C (p.D444H) |
N |
≈ N |
Hz |
3.1 |
NS |
| 32 |
F |
c.1330G > C (p.D444H) |
N |
≈ N |
Hz |
3.8; 2.7 |
S |
| 33 |
M |
c.1413 T > C (p.C471C) |
N |
N |
Borderline (Hz/N) |
0.1; 2.6; 4.9 |
NS |
| 34 |
F |
N |
N |
N |
Hz |
4.1 |
S |
| 35 |
M |
N |
N |
N |
Hz |
3.7 |
S |
| 36 |
F |
c.1330G > C (p.D444H) |
c.119 T > C (p.L40P) |
Unknown |
Partial |
1.7 |
NS |
| 37 |
M |
c.1330G > C (p.D444H) |
c.479G > A (p.C160Y) |
Unknown |
Borderline (Partial/Hz) |
0.2; 1.7; 2.2 |
NS |
| 38 | M | c.664G > A (p.D222N) | N | Unknown | Hz | 3.5 | NS |
aThe cutoff for filter-paper tests performed at laboratory A is 70U. For quantitative testing in serum or plasma performed at laboratories B, C, D, the measurement unit is nmol/min/mL and the reference range is 5.0-10. Unless otherwise specified, the unit of enzyme activity is nmol/min/mL.
bThe following enzyme activity ranges were used for phenotypic classification: <0.75, profound deficiency; 0.75-2.25, partial deficiency; 2.26-5.0, heterozygosity. If more than one measurement was obtained, the highest value was considered. Values within ± 0.1 of a cutoff point were classified as borderline.
cPatients with consanguineous parents.
dWhether it is in cis or trans configuration with the other variant found remains undetermined.
Novel variants shown in bold type, and synonymous variants, in italics.
BD, biotinidase deficiency; F, female; M, male; NS, neonatal screening; S, symptoms; Hz, heterozygosity; N/A, not available; N, normal.