Table 1.
Genetic diagnosis, ADA2 enzyme activity and clinical data of ADA2-deficient patients
| Kindred | Genetic diagnosis | ADA2 level mU/g protein | Age at sample | Viral phenotype | Treatment at sampling | Hypo-gamma | Type I IFN score | Major clinical phenotype at sampling | Other findings | |
|---|---|---|---|---|---|---|---|---|---|---|
| 1 | A | c.973-2 T > C / c. del1240-1442 | 1.1 | 8y6m | Warts, mollusca | (-) SCIG, amoxicilline | y | 19 | V (livedo), W, N, T, AIHA, | Severe AE to CPV |
| 2 | A | c.973-2 T > C / c. del1240-1442 | 2.7 | 10y8m | Warts, mollusca | (-) | y | 7 | V (livedo), R, | |
| 3 | B | c.140G > T (p.Gly47Val)/ c.506G > A(p.Arg169Gln) | 3.3 | 1y10m | (-) | n | 4 | None; now V (livedo), CNS, N, | ||
| 4 | B | c.140G > T (p.Gly47Val)/ c.506G > A(p.Arg169Gln) | 2.1 | 4y8m | Etanercept | y | 22,5 | V (livedo, cutaneous papules), now N | ||
| 5 | C | c.973-2 T > C / c.973-2 T > C | 1.6 | 5y8m | Etanerecept | n | 5 | V (livedo | ||
| 6 | D | p.Gly47Arg / p.Gly47Arg | 1.9 | 11y11m | Tocilizumab | n | 3 | Castleman disease V (livedo), | Later: CNS microbleeds, testicular thrombosis | |
| 7 | E | c.506G > A, c.1358A > G | 2.6 (2.6 HPLC) | 33y5m | Recurrent VZV, warts |
Prednisone 7.5 mg daily, IVIG (previously received mtx, cpm, mmf) |
y | 4.3* | DVT at 10y, V intestinal, S, CNS at 16y, HT | AE to UPV, Candida infections esophagus, skin, nails |
| 8 | E | c.506G > A, c.1358A > G | 0 (2.9 HPLC) | 40y | Viral encephalitis, Shingles | (-) | y | 6.7* | CNS at 3,5y, V, HT | AE to UPV |
| 9 | E | c.506G > A, c.1358A > G | 2.1 HPLC | 44y | Shingles, EBV | (-) | y (IgM) | 6.95* | V | AE to UPV |
| 10 | F | c.1397_1403del;c.1397_1403del p.Lys466Thrfs*2/p.Lys466Thrfs*2 | 0 (2.9 HPLC) | 42y | (-) recent EBV and HSV1, not at sampling | SCIG | y | 15.5* | P, HSM, A | Hepatitis (not at sampling) |
A Alopecia; AE adverse event; AIHA auto-immune hemolytic anemia; CNS central nervous system vasculitis manifestation, lacunar infarction, cranial nerve palsy, stroke, hemorrhage; cpm cyclophosphamide; CPV conjugated pneumococcal vaccine; DVT deep venous thrombosis; HG hypogammaglobulinemia; HSM hepatosplenomegaly; HT hypertension; IVIG intravenous immunoglobulins; mtx methotrexate; mmf mofetil mycophenolate; N neutropenia; P pancytopenia; R Raynaud phenomenon; S splenomegaly; SCIG subcutaneous immunoglobulins; T thrombocytopenia; UPV unconjugated pneumococcal vaccine; V vasculitis
*IFN score analyses performed in Sydney site