Patients with complete AR IFNAR1 and IFNAR2 deficiency reported to date
| Patient (kindred) . | Mutation . | Origin . | Age at presentation . | MMR (Y/N) . | MMR disease . | Other LAV . | COVID-19/influenza . | Other . | HLH . | Outcome . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation in IFNAR1 | |||||||||||
| 1(I) | Homozygous c.674-2A>G | Iran | 12 mo | Y | Disseminated, encephalitis | CMV | A | Hernandez et al. (2019) | |||
| 2(I) | Not genotyped | 12 mo | Y | Disseminated | Fatal | ||||||
| 3(II) | p.W261X and c.674-1G>A | Brazil | 14 yr | Y | Uneventful | YFV: disseminated disease: BCG and oral polio, uncomplicated | Seroconversion to CMV, HSV1, HSV2 | A | |||
| 4(III) | Complete homozygous deletion from intron 10 to exon 11 and 3′UTR | Palestinian territory | 13 mo | Y | Prolonged fever, spontaneous recovery | Gingivostomatitis and aseptic meningitis, HSE at 19 mo, fatal at 20 mo | Fatal | Bastard et al. (2021a) | |||
| 5(III) | Complete homozygous deletion of intron 10 to exon 11 and 3′UTR | 6 mo | N | Meningitis with deafness age 14 yr after mumps? | |||||||
| 6(III) | Not genotyped | 12 mo | Y | Disseminated disease | Fatal | ||||||
| 7 (IV) | p.Ser422Arg;p.Ser422Arg | Saudi Arabia | 26 yr | ? | Fatal COVID-19 | Fatal | Zhang et al. (2020) | ||||
| 8(V) | p.Trp73Cys;p.Trp73Cys | Turkey, Pakistan | 38 yr | ? | Critical COVID-19 | ||||||
| 9(VI) | p.Gln308Ter;p.Gln308Terr | ? | 15 mo | Y | Encephalitis, with cerebral atrophy (no vaccine strain viruses in CSF/serum) | Seroconversion to EBV, HSV, CMV | Y | Fatal | Gothe et al. (2022) | ||
| 10(VII) | p.H263fs*;H263 fs* | Iran | 8 mo | Y | N | BCG, oral polio, uncomplicated | Critical COVID-19 (MIS-C + pneumonia) | 8 mo chronic RTI, age 2 yr mucormycosis of nose and sinuses | Y | Abolhassani et al. (2022) | |
| 11(VIII) | Homozygous c.674-2A>G | Iran | 12 mo | Y | Meningitis | Critical COVID-19; recurrent influenza | A | Khanmohammadi et al. (2022) | |||
| 12(IX) | p.Glu386*;p.Glu386* | West Polynesia | 12 mo | Y | Meningoencephalitis, disseminated | BCG, oral polio, uncomplicated | Y | Fatal | Bastard et al. (2022) | ||
| 13(IX) | p.Glu386*;p.Glu386* | West Polynesia | 12 mo | Y | Meningoencephalitis, disseminated | Y | Fatal | ||||
| 14(X) | p.Glu386*;p.Glu386* | West Polynesia | 8 wk | Y, MMR-V | Meningoencephalitis, disseminated | Enterovirus meningoencephalitis | Y | Fatal | |||
| 15(XI) | p.Glu386*;p.Glu386* | West Polynesia | 13 mo | Y | Meningoencephalitis, disseminated | Neonatal CMV, recovered; reactivation CMV hepatitis during MMR disease, parainfluenzavirus 1 + during MMR disease | Y | Fatal | |||
| 16(XI) | p.Glu386*;p.Glu386* | West Polynesia | 16 mo | Y | Meningoencephalitis | Enteroviral meningitis, second MMR tolerated; hospitalized 4× for bronchiolitis | Y | A | |||
| 17(XII) | p.Glu386*;p.Glu386* | West Polynesia | 14 mo | Y | Meningoencephalitis | 21 mo viral pneumonia + PCR rhinovirus, parainfluenzavirus, RSV, and bocavirus | ? | A | |||
| 18(XII) | p.Glu386*;p.Glu386* | West Polynesia | 10 mo | Y; MMR, MMR-V | No | Hib bacteremia and meningitis, RSV + at PCR with multiple organ failure, 2× bronchiolitis <12 mo; adv and hMPV resp exacerbation | N | A | |||
| Mutation in IFNAR2 | |||||||||||
| 1(I) | p.E104fs110X; p.E104fs110X | UK | 13 mo | Y | Meningoencephalitis | HHV6: uncomplicated infection, seroconversion for CMV, EBV | ? | Fatal | Duncan et al. (2015) | ||
| 2(I) | p.E104fs110X; p.E104fs110X | UK | Neonatal diagnosis | N | / | ? | A | ||||
| 3(II) | c.840+1 G>T; c.840+1 G>T | Brazil | 13 yr | ? | Uneventful | YFV: disease | A | Bastard et al. (2021b) | |||
| 4(II) | ? | Brazil | 19 yr | ? | / | YFV: disease, fatal at 19 yr | Fatal | ||||
| 5(III) | p.Leu79Ter;p.Ile185MetfsTer12 | Italy | 22 mo | Y | Trigger for HLH | Influenza pneumonia | Flu, HSV + pneumonia | Y | A | Passarelli et al. (2020) | |
| 6(IV) | p.Ser53Pro;p.Ser53Pro | Greenland | 22 mo | Y | Meningoencephalitis | BCG:uncomplicated | EBV reactivation, VZV, HSV1, CMV | ? | Duncan et al. (2022) | ||
| 7(V) | p.Ser53Pro;p.Ser53Pro | Nunavik | 12 mo | Y | Meningoencephalitis | BCG: rotavirus vaccine uncomplicated | Fatal COVID-19 | Uncomplicated hand foot mouth disease with herpangina, HSV1 stomatitis | Fatal | ||
| 8(V) | p.Ser53Pro;p.Ser53Pro | Nunavik | 5 yr | Y | Uneventful | Self-limiting COVID-19 | A | ||||
| 9(VI) | p.Ser53Pro;p.Ser53Pro | Alaska | 8 mo | Y | ? | VZV vaccine: disseminated disease | Relapsing COVID-19 | Fatal at 3 yr (neurological disease) | |||
| 10(VI) | p.Ser53Pro;p.Ser53Pro | Alaska | 13 mo | Y | Disseminated disease | VZV vaccine: disseminated disease | Adv, RSV, CMV, EBV, HHV6, HSV1 (+ in BAL at the time of LAV disease) | Fatal | |||
| Patient (kindred) . | Mutation . | Origin . | Age at presentation . | MMR (Y/N) . | MMR disease . | Other LAV . | COVID-19/influenza . | Other . | HLH . | Outcome . | Reference . |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mutation in IFNAR1 | |||||||||||
| 1(I) | Homozygous c.674-2A>G | Iran | 12 mo | Y | Disseminated, encephalitis | CMV | A | Hernandez et al. (2019) | |||
| 2(I) | Not genotyped | 12 mo | Y | Disseminated | Fatal | ||||||
| 3(II) | p.W261X and c.674-1G>A | Brazil | 14 yr | Y | Uneventful | YFV: disseminated disease: BCG and oral polio, uncomplicated | Seroconversion to CMV, HSV1, HSV2 | A | |||
| 4(III) | Complete homozygous deletion from intron 10 to exon 11 and 3′UTR | Palestinian territory | 13 mo | Y | Prolonged fever, spontaneous recovery | Gingivostomatitis and aseptic meningitis, HSE at 19 mo, fatal at 20 mo | Fatal | Bastard et al. (2021a) | |||
| 5(III) | Complete homozygous deletion of intron 10 to exon 11 and 3′UTR | 6 mo | N | Meningitis with deafness age 14 yr after mumps? | |||||||
| 6(III) | Not genotyped | 12 mo | Y | Disseminated disease | Fatal | ||||||
| 7 (IV) | p.Ser422Arg;p.Ser422Arg | Saudi Arabia | 26 yr | ? | Fatal COVID-19 | Fatal | Zhang et al. (2020) | ||||
| 8(V) | p.Trp73Cys;p.Trp73Cys | Turkey, Pakistan | 38 yr | ? | Critical COVID-19 | ||||||
| 9(VI) | p.Gln308Ter;p.Gln308Terr | ? | 15 mo | Y | Encephalitis, with cerebral atrophy (no vaccine strain viruses in CSF/serum) | Seroconversion to EBV, HSV, CMV | Y | Fatal | Gothe et al. (2022) | ||
| 10(VII) | p.H263fs*;H263 fs* | Iran | 8 mo | Y | N | BCG, oral polio, uncomplicated | Critical COVID-19 (MIS-C + pneumonia) | 8 mo chronic RTI, age 2 yr mucormycosis of nose and sinuses | Y | Abolhassani et al. (2022) | |
| 11(VIII) | Homozygous c.674-2A>G | Iran | 12 mo | Y | Meningitis | Critical COVID-19; recurrent influenza | A | Khanmohammadi et al. (2022) | |||
| 12(IX) | p.Glu386*;p.Glu386* | West Polynesia | 12 mo | Y | Meningoencephalitis, disseminated | BCG, oral polio, uncomplicated | Y | Fatal | Bastard et al. (2022) | ||
| 13(IX) | p.Glu386*;p.Glu386* | West Polynesia | 12 mo | Y | Meningoencephalitis, disseminated | Y | Fatal | ||||
| 14(X) | p.Glu386*;p.Glu386* | West Polynesia | 8 wk | Y, MMR-V | Meningoencephalitis, disseminated | Enterovirus meningoencephalitis | Y | Fatal | |||
| 15(XI) | p.Glu386*;p.Glu386* | West Polynesia | 13 mo | Y | Meningoencephalitis, disseminated | Neonatal CMV, recovered; reactivation CMV hepatitis during MMR disease, parainfluenzavirus 1 + during MMR disease | Y | Fatal | |||
| 16(XI) | p.Glu386*;p.Glu386* | West Polynesia | 16 mo | Y | Meningoencephalitis | Enteroviral meningitis, second MMR tolerated; hospitalized 4× for bronchiolitis | Y | A | |||
| 17(XII) | p.Glu386*;p.Glu386* | West Polynesia | 14 mo | Y | Meningoencephalitis | 21 mo viral pneumonia + PCR rhinovirus, parainfluenzavirus, RSV, and bocavirus | ? | A | |||
| 18(XII) | p.Glu386*;p.Glu386* | West Polynesia | 10 mo | Y; MMR, MMR-V | No | Hib bacteremia and meningitis, RSV + at PCR with multiple organ failure, 2× bronchiolitis <12 mo; adv and hMPV resp exacerbation | N | A | |||
| Mutation in IFNAR2 | |||||||||||
| 1(I) | p.E104fs110X; p.E104fs110X | UK | 13 mo | Y | Meningoencephalitis | HHV6: uncomplicated infection, seroconversion for CMV, EBV | ? | Fatal | Duncan et al. (2015) | ||
| 2(I) | p.E104fs110X; p.E104fs110X | UK | Neonatal diagnosis | N | / | ? | A | ||||
| 3(II) | c.840+1 G>T; c.840+1 G>T | Brazil | 13 yr | ? | Uneventful | YFV: disease | A | Bastard et al. (2021b) | |||
| 4(II) | ? | Brazil | 19 yr | ? | / | YFV: disease, fatal at 19 yr | Fatal | ||||
| 5(III) | p.Leu79Ter;p.Ile185MetfsTer12 | Italy | 22 mo | Y | Trigger for HLH | Influenza pneumonia | Flu, HSV + pneumonia | Y | A | Passarelli et al. (2020) | |
| 6(IV) | p.Ser53Pro;p.Ser53Pro | Greenland | 22 mo | Y | Meningoencephalitis | BCG:uncomplicated | EBV reactivation, VZV, HSV1, CMV | ? | Duncan et al. (2022) | ||
| 7(V) | p.Ser53Pro;p.Ser53Pro | Nunavik | 12 mo | Y | Meningoencephalitis | BCG: rotavirus vaccine uncomplicated | Fatal COVID-19 | Uncomplicated hand foot mouth disease with herpangina, HSV1 stomatitis | Fatal | ||
| 8(V) | p.Ser53Pro;p.Ser53Pro | Nunavik | 5 yr | Y | Uneventful | Self-limiting COVID-19 | A | ||||
| 9(VI) | p.Ser53Pro;p.Ser53Pro | Alaska | 8 mo | Y | ? | VZV vaccine: disseminated disease | Relapsing COVID-19 | Fatal at 3 yr (neurological disease) | |||
| 10(VI) | p.Ser53Pro;p.Ser53Pro | Alaska | 13 mo | Y | Disseminated disease | VZV vaccine: disseminated disease | Adv, RSV, CMV, EBV, HHV6, HSV1 (+ in BAL at the time of LAV disease) | Fatal | |||
A, alive; BAL, broncho-alveolar lavage; CSF, cerebrospinal fluid; BCG, bacille Calmette-Guerin; RSV, respiratory syncytial virus; RTI, respiratory tract infection; adv, adenovirus; resp, respiratory; hMPV, human metapneumovirus; HHV6, human herpes virus 6; HLH, hemophagocytic lymphohistiocytosis/inflammation; MIS-C, multisystem inflammatory syndrome in children, N, no; Y, yes.