Interleukin-12 receptor β1 (IL-12Rβ1) deficiency is a recessive defect predisposing to infections mainly with Salmonella and mycobacteria with a mortality around 30%. IL-12Rβ1 accounts for about half of all cases of Mendelian susceptibility to mycobacterial disease reported worldwide. We identified 10 patients. The United States has a low consanguinity rate, low tuberculosis rate and BCG vaccination, all factors that might affect clinical presentation
Serie of cases
Pt | mutation | Infections/age | Outcome age |
1 | c.512A>C, p.Q171P c.1442A>G, p.Y481C | MAC/5 | Died (10 years) Disseminated MAC |
2 | c.512A>C, p.Q171P c.1442A>G, p.Y481C | Extrapulmonary Histoplasma/27 MAC/47 | Alive (50 years) |
3 | Homozygous c.1495C>T p.Q499X | Extrapulmonary TB/4 Burkholderia vietenamiensis/41 | Died (42 years) HLH |
4.I | c.1398G>A pW466X c1623-1624delGCinsTT | MAC/1 | Alive( 9 years) Infection resolved Graft failure |
4.II | c.1398G>A W466X c1623-1624delGCinsTT | Asymptomatic | Alive (17 years) asymptomatic |
5 | Homozygous c94C>T, p.Q32X | Bordetella hinzii/18 | Alive (24 years) Infection resolved |
6 | Homozygous c.1623_1624delGCinsTT p Q542X | Coccidioides/14 | Alive (24years) persistent infection |
7.I* | Homozygous 557G>A C186Y | Salmonella/11yrs; Coccidioides/22 | Alive (25 years) Infections resolved (25years) |
7.II* | Homozygous 557G>A C186Y | Coccidioides/6 | Alive (21years)Infection resolved |
8** | 1623-1624delinsTT p Q541X | S. pneumoniae MAC /1.5 | Alive Persistent infection |
* Clin Infect Dis. 2011 Feb 15;52(4)
** J Allergy Clin Immunol. 2010 Jan;125(1):264-5
4I & 4II ; 8I & 8II siblings
In the United States IL-12Rβ1 deficiency is associated with disseminated infections including unusual organisms. US IL-12Rβ1 deficiency is likely underrecognized in part because of presentations with infections other than mycobacteria.