Table 1.
Clinical, genetic and biological characteristics of the 6 patients.
| Patient | Patient 1: | Patient 3: | Patient 6: | Patient 2 : | Patient 4: | Patient 5: | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Classical A-T | Classical A-T | Classical A-T | Variant AT | Variant AT | Variant AT | |||||||
| Current age | 7y | 10y | 4y | 29y | 25y | 14y | ||||||
| Age at diagnosis | 19mo | 9y | 20mo | 23y | 24y | 12y | ||||||
| ATM mutation (NM_000051.3) Variant 1 | c.2455T>C; (p.Cys819Arg) c.8264_8268del; (p.Tyr2755CysfsTer12) | c.7517_7520delGAGA; (p.Arg2506ThrfsTer3) c.8264_8268delATAAG; (p.Tyr2755CysfsTer12) | c.790delT; (p.Tyr264IlefsTer12) c.103C>T; (p.Arg35Ter). | c.6047A>G; (p.Asp2016Gly) c.6385T>G; (p.Tyr2129Asp) | c.6154G>A; (p.Glu2052Lys c.6355delG; (p.Val2119Ter) | c.6154G>A; (p.Glu2052Lys c.6355delG; (p.Val2119Ter) | ||||||
| Variant 2 | ||||||||||||
| Patient | Patient 1: | Patient 3: | Patient 6: | Patient 2 : | Patient 4: | Patient 5: | ||||||
| Classical A-T | Classical A-T | Classical A-T | Variant AT | Variant AT | Variant AT | |||||||
| Neurological assessment (Age at onset)* | Ataxia (18mo) Bradykinesia (18mo) | Ataxia (5y) Choreo-athetotic movements (6y) Oculomotor apraxia (9y) Axonal neuropathy (9y) Bradykinesia (9y) | Ataxia (11mo), dystonia (20mo), Dysarthria and drooling (3y) | Dysarthria (2-3y) Axial myoclonus (1-2 y) | Dysarthria (2y) Instability of independent walk (2-3y) Arms tremor, dystonia and choreo- athetotic | Instability of independent walk (7y) | ||||||
| Dystonia (19mo) Instability of independent walk (5y) | Mild axial and limb dystonia (16y) | movements | Dystonia and choreo-athetotic movements (12y) | |||||||||
| Resting tremor | ||||||||||||
| (16y) | ||||||||||||
| Mild axonal | ||||||||||||
| SARA T0a | NA | 13,5 | NA | 4 | 4 | 0 | ||||||
| T1a | 14 | 21 | 18,5 | 3 | 4 | 1 | ||||||
| ICARS T0a | NA | 35 | NA | 11 | 7 | 1 | ||||||
| T1a | 41 | 52 | 50 | 10 | 8 | 2 | ||||||
| Patient | Patient 1 (at 9mo): Classical A-T | Patient 3 (at 10y): Classical A-T | Patient 6 (at 20mo): Classical A-T | Patient 2 (at 25y): Variant AT | Patient 4 (at 24y): Variant AT | Patient 5 (at 13y): Variant AT | ||||||
| Ig levels (g/l): | 0.07 | N.V.* | 7.86 | N.V.* | 5.62 | N.V.* | 3.34 | N.V.* | 10.7 | N.V.* | 11.7 | N.V.* |
| IgG IgA | 0 | 3.7-11.7 | 0 | 6.5-14.6 | 0.3 | 3.8-17.9 | 0.16 | 16-Jul | 1.13 | 16-Jul | 2.05 | 6.5-14.6 |
| IgM | 1.03 | 0.17-1.32 | 2.4 | 0.7-4 | 0.8 | 0.17-1.32 | 0.24 | 0.7-4 | 0.63 | 0.7-4 | 1.08 | 0.7-4 |
| 0.31-1.34 | 0.4-2.3 | 0.31-1.34 | 0.4-2.3 | 0.4-2.3 | 0.4-2.3 | |||||||
| Vaccine-Abs Tetanus (UI/l) Diphtheria (UI/l) Measles (UI/l) Varicella (UI/l) S.pneumoniae (mg/l) | NA^ NA NA NA NA | N (1758) N (1079) N (648) N (702) | N (2194) N (446) NA | N (2496) N (316) N (200) N (227) All neg | N (1088) N (377) NA | N (2250) N (1001) NA | ||||||
| N (4/7 ≥0.5) ~ | No protection (<50) No protection (2/7) ~ | N (254) N (4/7) ~ | N (1542) N (7/7) ~ | |||||||||
| Lymphocyte Prolif. | N N NA NA | N N NA NA | N NA NA NA | N | N | N | ||||||
| Anti-CD3 | No response | No response | No response | |||||||||
| Tetanus | NA NA | N | N | |||||||||
| Candida albicans | No response | No response | ||||||||||
| S.pneumoniae | ||||||||||||
| Patient 1 (at 19mo) | Patient 3 (at 10y) | Patient 6 (at 20mo) | Patient 2 (at 25y) | Patient 4 (at 24y) | Patient 5 (at 13y) | |||||||
| Classical A-T | Classical A-T | Classical A-T | ||||||||||
| Lymphocyte Typing Lymphocytes T cells | Cell/mm | Cell/mm3 | Cell/mm | Cell/mm3 | Cell/mm | Cell/mm3 | Cell/mm | Cell/mm3 | Cell/mm | Cell/mm3 | Cell/mm | Cell/mm3 |
| CD4 | 3 | 1700-6900 | 3 | 1000-5300 | 3 | 1700-6900 | 3 | 1140-3380 | 3 | 1140-3380 | 3 | 1000-5300 |
| CD8 | 838 | 780-2240 | 1071 | 780-2240 | 1580 | 900-4500 | 1786 | 780-2240 | 1913 | 780-2240 | 1166 | 800-3500 |
| NK | 455 | 490-1640 | 649 | 490-1640 | 821 | 500-2400 | 1164 | 490-1640 | 1352 | 490-1640 | 790 | 400-2100 |
| B cells CD27+, IgD+ CD27+, IgD- CD38higIgMhi (transit) CD21low CD38low | 295 | 170-880 | 290 | 170-880 | 370 | 300-1600 | 570 | 170-880 | 946 | 170-880 | 517 | 200-1200 |
| 95 | 80-690 | 67 | 80-690 | 388 | 100-1000 | 370 | 80-690 | 293 | 80-690 | 208 | 70-1200 | |
| 173 | 200-2100 | 166 | 200-600 | 526 | 200-2100 | 40 | 80-490 | 69 | 80-490 | 77 | 200-600 | |
| 132 | 20-180 | 113 | 20-70 | 116 | 20-180 | 299 | Oct-80 | 416 | Oct-80 | 214 | 20-70 | |
| 1 | 20-220 | 16 | 30-110 | 12 | 20-220 | 159 | 20-90 | 63 | 20-90 | 16 | 30-110 | |
| 27 | 20-200 | 41 | Oct-60 | 16 | 5.7-28 | 42 | 0-30 | 81 | 1.6-30 | 18 | 11-111 | |
| 0 | Oct-60 | 0 | 30-Oct | 2 | Oct-60 | 0 | 20-Oct | 9 | 20-Oct | 19 | 30-Oct | |
| 16 | 28 | 10 | 26 | 43 | 14 | |||||||
| Patient 1 (at 19mo) Classical AT | Patient 3 (at 10y) Classical AT | Patient 6 (at 20mo) Classical AT | Patient 2 (at 25y) Variant AT | Patient 4 (at 24y) Variant AT | Patient 5 (at 13y) Variant AT | |||||||
| Alpha fetoprotein | 89.7 | 520-580 | 134 | 78 | 154 | 58.1 | ||||||
| (mcg/l) | ||||||||||||
| Other | Failure to thrive | Supraventricular tachycardia | Chronic constipation | Diabetes type 1 | Scoliosis, chronic nasal obstruction | Chronic constipation, Oral allergy syndrome and allergic rhinoconjunctivitis | ||||||
| Support/ Treatment | IVIG/SC Ig Gastrostomy Ergotherapy Physiotherapy, Speech therapy | Ergotherapy, Physiotherapy, Speech therapy | Osmotic laxatives (Macrogol), Speech and physio-therapy | Insulin | Antiparkinsonian agents (Levodopa+benserazi de), Physiotherapy, Septoplasty and turbinoplasty (2018) | Osmotic laxatives (Macrogol), Antihistamines symptomatic treatments | ||||||
*Age at onset years (y) or months (mo).
a
T0 neurological assessment at diagnosis.
b
T1 neurological assessment at current age.
*N.V. normal values for age.
^NA not applicable.
~Number of serotypes with protective antibodies (≥0.5 mg/l).
N normal (protective).
Values of lymphocyte subsets and immunoglobulin levels marked in boldface are less than the age-related normal value. For normal values of lymphocyte subsets, see (17).