Clinical and genetic characteristics of patients with ORAS.
| Reference (Year) | Patient | Gestational Age/Weight | Symptom Onset Age/Sex | Gene; AA Alteration | Mutation | Origin | Consanguinity | Symptoms | Treatment | Outcome |
|---|---|---|---|---|---|---|---|---|---|---|
| Damgaard1 (2016) | 1 | 34 wks | 3 wks/F | c.815T>C; Leu272Pro homozygous | Missense | Pakistani | 2nd cousins | • Protracted diarrhea, failure to thrive, nodular erythematous rash, severe pneumonia | • PSL, azathioprine, MTX | • Died at age 16 mos from pneumococcal septicemia |
| 2 | 36 wks/2000 g | 3 d/F | c.815T>C; Leu272Pro homozygous | Missense | Pakistani | 2nd cousins | • Relapsing nodular panniculitis, diarrhea, vomiting, fever, painful swollen joints, failure to thrive, bilateral cataracts | • PSL, anakinra | • Died at age 5 yrs from acute renal failure, pulmonary edema | |
| 3 | 28 + 6 wks/1230 g | 8 wks/M | c.815T>C; Leu272Pro homozygous | Missense | Pakistani | 2nd cousins | • Relapsing nodular panniculitis, fever, vomiting, diarrhea (sometimes bloody), inflamed painful joints, swollen feet, weight loss, juvenile cortical cataracts | • Systemic CS, anakinra, IFX, prophylactic azithromycin, acyclovir | • At age 11 yrs, successfully controlled with IFX for 8 yrs (> 5 mg/kg) | |
| Zhou2 (2016) | 4 | 38 wks | 4.5 mos/F | c.731A>G; Tyr244Cys homozygous | Missense | Turkish | Yes | • Prolonged fevers and pustular, scarring rashes | • CS, anakinra | • Symptoms improved on treatment with anakinra |
| 5 | NA | Neonatal/F | c.517delC; Glyl74Aspfs*2 homozygous | Frameshift | Turkish | Yes | • Erythematous rash with painful skin nodules, progressive lipodystrophy, failure to thrive | • CS, ETN | • CS-dependent | |
| Damgaard4 (2019) | 6 | NA | 3 d/F | c.841G>A; p.Gly281Arg homozygous | Missense | Arab | 1st cousins | • Recurrent fever, widespread panniculitis, diarrhea, failure to thrive, severe splenomegaly, bilateral cataracts | • Prednisone, colchicine, anakinra, HSCT | • Relapse at age 9 mos after HSCT, under control with ETN (0.4 mg/kg, twice weekly) |
| Nabavi3 (2019) | 7 | 35 wks/NA | Neonatal/F | c.864+2T> chomozygous | Frameshift | Iranian | 1st cousins | • Erythematous nodules, abscesses without fever, highgrade fever with respiratory distress, mild hepatosplenomegaly | • Antibiotic therapy, IFN-γ | • Died at age 8.5 mos from pulmonary edema |
| Zinngrebe5 (2022) | 8 | NA | 7 yrs/M | c.25SG>A; p.M86I/c.500G>C; P.W167S compound heterozygous | Missense | Greek | No | • Late-onset, sterile abscess formation in different organs (skin, lung, spleen) | • Antibiotic therapy, CS | • Alive and in good condition |
| Caballero-Oteyza6 (2024) | 9 | NA | Neonatal/M | c.595T>A; p.Trpl99Arg homozygous | Missense | Moroccan | Yes | • Failure to thrive, severe, sterile systemic inflammation | • Antibiotic therapy, CS | • Died soon after the neonatal period |
| Takeda9 (2024) | 10 | NA | Neonatal/F | c.917G>A; p.Arg306Gln heterozygous | De novo | Japanese | No | • Persistent fever, erythema nodosum-like skin eruptions, unresolving omphalitis and ARDS | • CS, ETN | • CS-free remission, catching up in physical growth |
| Davidson8 (2024) | 11 | 31 wks/NA | 4 d/M | c.386G>C; p.Cys129Ser heterozygous | De novo | Caucasian | No | • Periumbilical abscess (positive culture with methicillin-Sensitive S. aureus), ARDS, sterile pustular abscesses | • CS, ADA, ruxolitinib, broad-spectrum antibiotic prophylaxis | • At age 2 yrs, controlled with low-dose CS, ADA weekly, and ruxolitinib |
| 12 | Term/NA | 7 mos/F | c.38ST>A; p.Cys129Ser heterozygous | De novo | Saudi | No | • Multiple tender skin lesions, fever, generalized edema, necrotizing fasciitis with ulceration | • Antibiotic therapy, IFX, MTX, CS | • At age 3 yrs, in clinical and biochemical remission since starting TNFi 2 yrs prior |
AA: amino acid.; ADA: adalimumab; ARDS: acute respiratory distress syndrome; CS: corticosteroid; ETN: etanercept; HSCT: hematopoietic stem cell transplantation; IFN: interferon; IFX: infliximab; MTX: methotrexate; NA: not applicable; ORAS: OTULIN-related autoinflammatory syndrome; PSF: prednisolone; S. aureus: Staphylococcus aureus, TNFi: tumor necrosis factor inhibitor.