Introduction
Methods
N° | sex | Origin | C | ADA mutation | Treatment | Years of follow-up § (age) |
---|---|---|---|---|---|---|
1 | F | South America/Hispanic | Yes | Compound heterozygous, c.320 T > C, p.L107P/c.632G > A, p.R211H | Haploidentical BMT° ➔ GT1➔PEG-ADA | 15 (3–18 y) |
2 | M | South America/Hispanic | No | Compound heterozygous, c.221G > T, p.G74V/c.845G > A, p.R282Q | Haploidentical BMT° ➔ GT1 | 14 (1–15 y) |
3 | F | Arabic/White | Yes | Homozygous c.845G > A, p.R282Q | Haploidentical BMT° ➔ PEG-ADA ➔ GT1 | 13 (1–14 y) |
4 | F | Arabic/White | Yes | Compound heterozygous, c.646G > A, p.G216R/c.956_960delAAGAG; p.E319GfsX3 | PEG-ADA ➔ GT1 | 11 (1–12 y) |
5 | M | Europe/White | Yes | Homozygous c.632G > A, p.R211H | PEG-ADA ➔ GT1 | 12 (5–17 y) |
6 | M | Europe/White | No | Compound heterozygous, c.646G > A, p.G216R/c.872C > T, p.S291L | PEG-ADA ➔ GT1 | 11 (0–11 y) |
7 | M | Europe/White | No | Homozygous c.478 + 2 T > C | PEG-ADA ➔ GT1 | 10 (1–11 y) |
8 | F | Arabic/White | Yes | Homozygous c.646G > A, p.G216R | Haploidentical BMT° ➔ PEG-ADA ➔ GT1 | 8 (0–8 y) |
9 | M | South America/Hispanic | Yes | Homozygous c.632G > A, p.R211H | PEG-ADA ➔ GT1 | 9 (0–9 y) |
10 | M | North America/White | No | Compound heterozygous, c.646G > A, p.G216R/c.956_960delAAGAG; p.E319GfsX3 | PEG-ADA ➔ GT1 | 9 (1–10 y) |
11 | M | South Asia | Yes | Homozygous c.606 + 5G >? (Exon6, splice donor site + 5— no more data available) | PEG-ADA ➔ GT1 | 9 (0–9 y) |
12 | M | North America/White | No | Compound heterozygous, c.646G > A, p.G216R/Exon10, deletion + 6 c.975 + 6Tdel | PEG-ADA ➔ GT1 | 8 (6–14 y) |
13 | F | Africa/White | No | Homozygous: c.466C > T, p.R156C | PEG-ADA ➔ GT1 | 8 (2–10 y) |
14 | M | Africa/Black | No | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT1 | 6 (2–8 y) |
15 | M | Africa/Black | Yes | Homozygous, c.881C > A, p.T294K | PEG-ADA ➔ GT1 ➔ MSD BMT2 | 4 (1–5 y) |
16 | M | Arabic/White | Yes | Homozygous, c.956_960delAAGAG, p.E319GfsX3 | PEG-ADA ➔ GT1 | 5 (2–7 y) |
17 | F | European/White | No | Compound heterozygous, c.632G > A, p.R211H/c.646G > A, p.G216R | PEG-ADA ➔ GT1 | 2 (0–2 y) |
18 | M | Europe/Hispanic | No | Compound heterozygous, c.467G > A, p.R156H / c.646G > A, p.G216R | PEG-ADA ➔ GT1 ➔ MUD BMT* | 3 (2–5 y) |
19 | M | Europe/White | Yes | Compound heterozygous, c.385G > A, p.V129M /(second mutation not identified) | PEG-ADA | 16 (14–30 y) |
20 | F | Europe/White | Unk | Homozygous, c.385G > A, p.V129M | PEG-ADA | 23 (4–27 y) |
21 | F | Europe/White | No | Homozygous, c.499delG, pV167P | PEG-ADA | 12 (6–18 y) |
22 | M | Europe/White | Yes | Homozygous, c.632G > A, p.R211H | PEG-ADA | 17 (3–20 y) |
23 | M | Europe/White | Yes | Homozygous, c.632G > A, p.R211H | PEG-ADA ➔ MSD BMT3 | 10 (0–10 y) |
24 | M | Europe/White | Unk | Homozygous, c.632G > A, p.R211H | PEG-ADA ➔ MSD BMT° | 6 (5–10 y) |
25 | M | South America/Hispanic | No | Homozygous, c.845G > A, p.R282Q | PEG-ADA ➔ MUD BMT° | 1 (0–1 y) |
26 | F | Europe/White | Unk | Exon 3, insertion (no more data available) | PEG-ADA ➔ MSD BMT° | 14 (0–14 y) |
27 | M | Europe/White | No | Compound heterozygous, c.466C > T, p.R156C/c.955_959GAAGA, p.E320GfsX3 | PEG-ADA ➔ MUD BMT° | 13 (1–14 y) |
28 | M | Europe/White | Unk | ND | Haploidentical BMT* | 15 (0–15 y) |
29 | F | Europe/White | Unk | ND | PEG-ADA ➔ MUD BMT* | 11 (0–11 y) |
30 | F | South Asia | Unk | Homozygous, c.424C > T, p.R142X | PEG-ADA ➔ MSD BMT° | 13 (0–13 y) |
31 | M | Unk | Unk | Homozygous, c.424C > T, p.R142X | PEG-ADA ➔ MSD BMT° | 17 (0–17 y) |
32 | F | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ MSD BMT° | 18 (0–18 y) |
33 | M | Europe/White Irish | Unk | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT° | 17 (0–17 y) |
34 | F | South Asia | Yes | ND | PEG-ADA ➔ MFD BMT° | 18 (0–18 y) |
35 | F | Europe/White | Unk | Compound heterozygous, c.363-1G > C/c.364G > A, p.G122R | PEG-ADA ➔ MUD BMT4 | 18 (0–18 y) |
36 | M | Europe/White | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT° | 17 (0–17 y) |
37 | F | Europe/White | Yes | ND | PEG-ADA ➔ MSD BMT° | 16 (0–16 y) |
38 | F | Europe/White Irish | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT° | 15 (0–15 y) |
39 | M | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT5 | 17 (0–17 y) |
40 | M | Africa/Black | No | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ MFD BMT° | 14 (0–14 y) |
41 | M | Africa/Black | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MSD BMT° | 13 (0–13 y) |
42 | F | Africa/Black | No | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ MUD BMT6 | 14 (0–14 y) |
43 | M | South Asian heritage | Yes | Homozygous, c.716G > A, p.G239D | PEG-ADA ➔ MSD BMT° | 12 (0–12 y) |
44 | M | Europe/White | No | Compound heterozygous, c.367delG, p.D123TfsX10/c.956_960delAAGAG; p.E319GfsX3 | PEG-ADA ➔ GT5 | 13 (0–13 y) |
45 | F | Europe/White | No | Compound heterozygous, c.467G > A, p.R156H/c.478 + 1G > A | PEG-ADA ➔ GT (first)5 ➔ GT (second)7 | 13 (2–15 y) |
46 | M | South Asia | Yes | Homozygous, c.716G > A, p.G239D | PEG-ADA ➔ MSD BMT° | 11 (0–11 y) |
47 | F | Europe/White | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT° | 11 (1–12 y) |
48 | M | Arabic /white | Yes | Homozygous, c.956_960delAAGAG; p.E319GfsX3 | PEG-ADA ➔ GT5 | 8 (0–8 y) |
49 | M | Arabic/White | Yes | Homozygous, c.385G > A, p.V129M | PEG-ADA ➔ MSD BMT° | 5 (1–6 y) |
50 | M | Europe/White | No | ND | PEG-ADA ➔ GT5 | 3 (1–4 y) |
51 | F | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ MSD Cord° | 10 (0–10 y) |
52 | M | Africa/Black | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT5 | 11 (0–11 y) |
53 | F | South Asia | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MMUD Cord8 | 9 (0–9 y) |
54 | F | South Asia | Yes | Homozygous, c.703C > T, p.R235W | PEG-ADA ➔ MMUD Cord8 | 10 (0–10 y) |
55 | M | Arabic/White | Yes | Homozygous, c.428dupA, p.D143EfsX28 | PEG-ADA ➔ MUD Cord8 | 3 (0–3 y) |
56 | M | Europe/White | No | Compound heterozygous, c.466C > T, p.R156C/c.646G > A, p.G216R | PEG-ADA ➔ GT5 ➔ HSCT7 | 12 (1–13 y) |
57 | M | South Asia | Yes | Homozygous, c.646G > A, G216R | PEG-ADA ➔ MUD Cord ➔ MUD PBSC9 | 9 (0–9 y) |
58 | F | South Asia | Yes | Homozygous, c.716G > A, p.G239D | PEG-ADA ➔ MFD BMT° | 7 (0–7 y) |
59 | M | Europe/White | No | Compound heterozygous, c.955-958delGAAG, p.E320RfsX6/c.1078 + 2 T > A | PEG-ADA ➔ GT (first) ➔ GT (second) | 8 (4–12 y) |
60 | F | Arabic/White | Yes | Homozygous, 1079-15 T > A | PEG-ADA ➔ MUD PBSC5 | 3 (1–4 y) |
61 | M | Arabic/White | Yes | Homozygous, c.385G > A, p.V129M | PEG-ADA ➔ MFD BMT10 | 4 (0–4 y) |
62 | M | Europe/White Irish | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT0 | 7 (0–7 y) |
63 | M | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 3 (4–7 y) |
64 | M | South Asia | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 7 (0–7 y) |
65 | F | Europe/White | No | Compound heterozygous, c.646G > A, p.G216R/c.955_959GAAGA, p.E320GfsX3 | PEG-ADA ➔ GT7 | 5 (0–5 y) |
66 | F | South Asia | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 5 (0–5 y) |
67 | M | Arabic/white | No | Compound heterozygous, c.976-1G > C/c.302G > T, p.R101L | PEG-ADA ➔ GT (first) 7 ➔ GT (second) 7 | 9 (1–10 y) |
68 | M | Africa/Black | No | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 4 (0–4 y) |
69 | F | Europe/White | No | Compound heterozygous, c.872C > T, p.S291L/c.986C > T, p.A329V | PEG-ADA ➔ GT7 | 4 (1–5 =y) |
70 | M | Africa/Black | No | Homozygous: c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 4 (0–4 y) |
71 | M | Africa/Black | No | Compound heterozygous, c.603C > G, p.Y201X/c.632G > A, p.R211H | PEG-ADA ➔ GT7 | 4 (0–4 y) |
72 | F | Africa/Black | No | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 4 (9–13 y) |
73 | F | Europe/White Irish | Yes | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 2 (0–2 y) |
74 | M | Europe/White | No | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ MFD BMT ➔ MSD BMT° | 2 (0–2 y) |
75 | M | Unk | No | Compound heterozygous, c.320 T > C, p.L107P/c.632G > A, p.R211H | PEG-ADA ➔ GT7 | 1 (1–2 y) |
76 | F | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 3 (0–3 y) |
77 | M | Europe/White Irish | No | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 2 (0–2 y) |
78 | M | Europe/White | Yes | Compound heterozygous, c.310C > A, p.P104T/c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 2 (0–2 y) |
79 | F | Europe/White | Yes | Compound heterozygous, c.43C > G, p.H15D/c.757_758dupCG | PEG-ADA ➔ GT7 | 2 (0–2 y) |
80 | F | Europe/White | No | Homozygous, c.646G > A, p.G216R | PEG-ADA ➔ GT7 | 2 (0–2 y) |
81 | M | Africa/White | No | Homozygous, c.704G > A, p.R235Q | PEG-ADA ➔ GT7 | 1 (2–3 y) |
82 | M | Europe/White Irish | Yes | Homozygous, c.646G > A, G216R | PEG-ADA ➔ GT7 | 2 (0–2 y) |
83 | F | Europe/White | No | Homozygous, c.320 T > C, p.L107P | PEG-ADA ➔ GT7 | 0 |
84 | M | Africa/Black | Yes | Homozygous, c.7C > T, p.Q3X | PEG-ADA ➔ GT7 | 1 (0–1 y) |
85 | F | Europe/White Irish | Yes | Homozygous, c.646G > A, G216R | PEG-ADA ➔ GT7 | 0 |
86 | F | Europe/White-Africa/Black | No | Compound heterozygous, c.482G > A, p.W161X/c.1078 + 2 T > A | PEG-ADA ➔ GT7 | 0 |
Results
N° | WG | CUT | AUT | Treatment of undescended testes | Other urogenital diseases | Puberty | Testis structure at US scan | Hypothalamus-pituitary-gonads axis |
---|---|---|---|---|---|---|---|---|
2 | ≥ 37 | Left | Right (9 y) | Left orchidopexy 2 y and 7 months Right orchidopexy 9 y and 11 months. No relapse | Phimosis | Pubescent at 15 y (G2P4) | Dyshomogeneous (hyporeflectant areas) since 14 y | Physiologic activation |
5 | 36 | Right | No | Right orchidopexy. No relapse | 1) Phimosis 2) inguinal hernia | Pubescent at 15 y G5 | Normal | Physiologic activation |
6 | 36 + 1 | Bilat | No | Bilateral orchidopexy 2 y and 3 months. No relapse | Phimosis | Prepubescent at 10 y | Normal | Not activated |
7 | ≥ 37 | No | No | NA | Phimosis | Prepubescent at 11 y | ND | Not activated |
9 | ≥ 37 | No | Right (6 y) | Right orchidopexy 7 y and 2 months. No relapse | Phimosis | Prepubescent at 9 y | Hyporeflectant areas since 13 y | Not activated |
10 | ≥ 37 | no | No | NA | No | Prepubescent at 8 y | ND | Not activated |
11 | ≥ 37 | Bilat | No | Gonadoreline not effective. Bilateral orchidopexy 3 y. Bilateral relapse Gonadoreline not effective. Left orchidopexy 5y 6mo. Bilateral relapse 7 y | 1) Phimosis 2) Micropenis 3) Posterior urethral valve left megaureter | Normal mini-puberty Prepubescent at 9 y | ND | Not activated |
12 | 32 | no | No | NA | No | Prepubescent at 13 y | Homogenous but less reflectant since 11 y | Not activated |
14 | ≥ 37 | Left | Bilat (7 y) | Congenital undescended testes spontaneously solved Bilateral orchidopexy 8 y. No relapse | Phimosis | Prepubescent at 8 y | Normal | Not activated |
15 | ≥ 37 | No | No | No | Phimosis | Prepubescent at 5 y | Homogenous but less reflectant since 11 y | Not activated |
16 | ≥ 37 | No | Bilat (3 y) | Bilateral orchidopexy 4y. Left relapse 5 y | No | Prepubescent at 7 y | Normal | Not activated |
19 | ≥ 37 | No | Right | Gonadoreline, effective. Right relapse right orchidopexy 13y + hernioplastic. No relapse | Inguinal hernia | Pubescent at 30 y G5 | Normal | Not activated |
22 | ≥ 37 | No | Left (2 y) | Spontaneously solved. No relapse | Inguinal hernia | Pubescent at 15 y G4 | ND | Not activated |
24 | ≥ 37 | No | Bilat (5 y) | Bilateral orchidopexy 5 y. No relapse | No | Pubescent—early onset (at 11 y G4) | Hyperreflectant spots (seminiferous tubule fibrosis) | Physiologic activation |
28 | Unk | No | No | NA | Micropenis | CDGP; 15 y after testosterone: G2P3A1 | Normal | ND |
31 | > 37 | Bilat | No | Unk | Micropenis | CDGP; at 17 y: G3P3A2 | Normal | Physiologic activation |
33 | Unk | No | No | NA | Micropenis | Unk | ND | ND |
36 | > 37 | No | No | NA | No | CDGP; at 17 y after testosterone: G4P4A2 | ND | ND |
40 | > 37 | No | No | NA | No | Prepubescent at 14 y | Normal | ND |
43 | > 37 | Bilat | No | 2 y bilateral orchidopexy | No | Pubescent at 12 y (G4P3A2), early onset | ND | ND |
57 | > 37 | Bilat | No | Not done yet—performing follow-up | Micropenis | Normal mini-puberty Prepubescent at 9 y | ND | ND |
59 | >37 | Right | No | 11 y right orchidopexy | Phimosis | Prepubescent at 11 y | ND | ND |
62 | Unk | Left | No | 18 months left orchidopexy | No | Prepubescent at 7 y | Normal | ND |
68 | > 37 | No | Right | 4 y right orchidopexy | No | Prepubescent 4 y and 7 months | Normal | Not activated |
82 | > 37 | Bilat | No | Not done yet—performing follow-up | Micropenis Undervirilized scrotum | Suspect hypogonadism hypogonadotropic (no mini-puberty) Prepubescent 1 y and 7 months | ND | ND |
N° | Pelvic us scan | Other urogenital disease | Pubertal stage | Precocious puberty | Treatment with GnRH agonist | Delayed puberty | Hypothalamus-pituitary-gonads axis |
---|---|---|---|---|---|---|---|
3 | Normal | No | Pubescent 15 y TS V RM | No | No | No | ND |
4 | Normal | No | Pubescent 12 y TS V RM | Yes (8 y) | Yes (8–11 y) | No | ND |
13 | Normal | No | Pubescent 10 y, B4 P2–3 | No | No | No | Physiologic activation |
17 | Normal | No | Prepubescent 3 y | No | No | No | ND |
20 | Normal | No | Pubescent RM | No | No | No | Physiologic activation |
21 | Normal | No | Pubescent IM# | Yes (8 y) | No | No | Physiologic activation |
42 | Normal | No | Pubescent 14 y, RM | No | No | No | Physiologic activation |
45 | Normal | Polycystic kidney disease | Pubescent at 15 y, RM | No | No | No | ND |
53 | Normal | No | Pubescent at 9 y, A1P2B3 | Yes (9 y) | Yes (9 y–ongoing) | No | Normal |
N° | Sex | Pubertal stage | Hypothalamus-pituitary-gonads axis |
---|---|---|---|
2 | M | Pubescent at 15 y (G2P4) | Physiologic activation |
5 | M | Pubescent at 15 y (G5) | Physiologic activation |
6 | M | Prepubescent at 10 y | Not activated |
7 | M | Prepubescent at 11 y | Not activated |
9 | M | Prepubescent at 9 y | Not activated |
10 | M | Prepubescent at 8 y | Not activated |
11 | M | Prepubescent at 9 y | Normal mini-puberty Not activated |
12 | M | Prepubescent at 13 y | Not activated |
13 | F | Pubescent 10 y, B4 P2–3 | Physiologic activation |
14 | M | Prepubescent at 8 y | Not activated |
15 | M | Prepubescent at 5 y | Not activated |
16 | M | Prepubescent at 7 y | Not activated |
19 | M | Pubescent at 30 y (G5) | Physiologic activation |
20 | F | Pubescent, regular menses | Physiologic activation |
21 | F | Pubescent, irregular menses (polycystic ovary syndrome) | Physiologic activation |
24 | M | Pubescent at 10 y (G1–2) | Physiologic activation |
42 | F | Pubescent 14 y, regular menses | Physiologic activation |
53 | F | Pubescent at 9 y: A1P2B3 | Physiologic activation |
57 | M | Prepubescent at 9 y | Normal mini-puberty Not activated |
82 | M | Prepubescent 1 y and 7 months | Suspected hypogonadotropic hypogonadism, no mini-puberty (testosterone treatment) |