Table 2.
Summary of clinical characteristics, treatment, and genotype in the 7 subjects with ADA2 deficiency from China
| P1 | P2 | P3 | P4 | P5 | P6 [13] | P7 [14] | |
|---|---|---|---|---|---|---|---|
| Gender | female | male | male | male | female | male | female |
| Age at onset/diagnosis | 3y/6y | 9y/16y | 2 m/6y | 6 m/1y | 1y/5y | 4y/8y | 3 m/13 m |
| CECR1 mutations | |||||||
| Paternal |
c.1232A > G, p.Y411Ca |
c.13G > C, p.G5Ra |
c.878A > C, p.H293Pa |
c.506G > A, p.R169Qa |
c.254A > T, p.N85Ia |
c.1072G > A, p.G358R |
c.1211 T > C, p.F404S |
| Maternal |
c.983A > T, p.N328I |
Exon7dela |
c.263A > G, p.Y88C |
c.393delG, p.R131Sfsb52 |
c.851G > T, p.G284V |
c.142G > A, p.G48R |
c.1114G > A, p.V372M |
| ADA2(U/L) | Not tested | 0 | 0.67b | 0.2 | 0 | Not tested | Not tested |
| ADA2(U/L) of Father/Mother | Not tested | Not tested / 1.58 | 5.86/3.01b | 1.8/3.44 | 1.91/2.17 | Not tested | Not tested |
| total ADA(U/L) | Not tested | 3.45 | Unscanned | 3.64 | 3.61 | Not tested | Not tested |
| Fever/Age at onset | Yes/3y | Yes/14y | Yes/2 m | Yes/6 m | Yes/2y | YES/4y | Yes/3 m |
| Skin symptom | Yes/3y | Yes/9y | Yes/2 m | Yes/7 m | Yes/2y | YES/4y | Yes/3 m |
| Erythema (on both lower limbs) | Erythema (Hip, all four limbs) | Erythematous papule (on face) | Livedo reticularis (on both lower limbs) | Erythema nodosum and Livedo reticularis (on both lower limbs) |
Erythema nodosum (face and all four limbs) Livedo reticularis (on left lower limbs) |
Erythema (on both lower limbs) Necrosis (on upper extremities) upper extremities |
|
| Neurological involvement | No | No | No | No |
2y/ hemorrhagic stroke at left basal ganglia Eye external oblique (right eye), abnormal gait |
4y/ ischemic stroke blepharoptosis (both eyes), Eye external oblique, abnormal gait |
1y/ ischemic stroke at right thalamus blurred vision (right eye) |
| Abdominal pain | Yes/3y | Yes/9y | No | No | Yes/5y | No | No |
| Nephrological involvement | No | Unilateral Hydronephrosis(left) | Hypertension and Microalbuminuria | No | No | No | No |
| Arthritis | No | No | No | No | 2y/ bilateral ankle joint | 4y/ bilateral ankle joint | No |
| Growth retardation | No | No | No |
YES/1y2m Wt 7.6 kg(<P3) Ht 67.5 cm(<P3) |
No | No |
YES/1y (unspecified) |
| Oral aphthous | No | No | No | No | Yes/2y | No | No |
| WBC(× 109/L) | 4.14 | 4.79 | 9.06 | 21 | 15.51 | 7 | N/A |
| HGB (g/L) | 122 | 124 | 120 | 98 | 132 | 90 |
Anemia (unspecified) |
| PLT(×109/L) | 224 | 118 | 429 | 132 | 392 | 413 | 454 |
| CRP (mg/L) | 3 | 11 | 80 | 43 | 115 | 59 | 49.98 |
| ESR (mm/h) | 9 | 6 | 95 | 49 | 74 | 16 | N/A |
| IL-6 (pg/ml) | N/A | 24.9 | Not tested | 33.3 | 230 | N/A | 120.85 |
| IL-8 (pg/ml) | N/A | N/A | Not tested | 11 | 27 | N/A | 135.25 |
| TNF-a (pg/ml) | N/A | 16.6 | Not tested | 22.8 | 41.6 | 23.3 | 2.79 |
| IgG (g/L) | 5.33 | 6.84 | 1.92↓ | 6.95 | 6.81 | Low(unspecified) | 10.24 |
| IgA (g/L) | 0.46 | 0.95 | 0.31 | 0.66 | 0.41 | N/A | 0.58 |
| IgM (g/L) | 0.31↓ | 0.23↓ | 0.17↓ | 1.07 | 0.56 | N/A | 0.72 |
| IgE (KU/L) | 36.3 | 64.5 | 27.14 | 24 | Unscanned | N/A | N/A |
| ANA | Negative | Negative | 6y/ANA 1:100; SSA/AMA (±) | Negative | Negative | N/A | N/A |
| CD3% | 70.5% | 76.8% | 69.3% | 22% | 84.5% | N/A | 51.8% |
| CD4% | 42.2% | 28.3% | 28.0% | 14% | 49.4% | N/A | 30.05% |
| CD8% | 21.7% | 40.6% | 28.4% | 7.4% | 31.6% | N/A | 18.45% |
| B% | 23.5% | 16.3% | 24.8% | 65% | 8.3% | N/A | 26.49% |
| NK% | 5.6% | 4.8% | 5.8% | 10.7% | 6.5% | N/A | 20.63% |
| Previous treatment | – | CS, MTX | CS, IVIG | CS, IVIG | CS, Colchicine, IVIG, TCZ | CS, MTX, CTX | CS, TCZ |
| Current treatment | Dipyridamole | MMF | MTX | Adalimumab | Etanercept | Anti TNF-α (unspecified) | HSCT |
a, reported previously in non-Chinese DADA2 patients; b, tested by ELISA at local hospital
Reference values for immunoglobulins (aged 1-6y): IgG 5-12 g/L, IgA 0.2–1.08 g/L, IgM 0.5–1.99 g/L
N/A Not available
CS Corticosteroid, CTX Cyclophosphamide, IVIG Intravenous Ig, NSAID Nonsteroidal anti-inflammatory drugs, MTX Methotrexate, MMF Mycophenolate mofetil, TCZ Tocilizumab, HSCT Hematopoietic stem cell transplantation