Table 1.
Clinical presentation and outcome of IKBKB immune deficiency.
| Patient | 1 | 2 | 3 | 4 | 5 | 6 |
|---|---|---|---|---|---|---|
| Decade of Diagnosis | 1970s | 1970s | 1980s | 2000s | 1990s | 2000s |
| IKBKB Mutation Confirmed | No | No | No | Yes | Yes | Yes |
| Direct Family Relationships to Known IKBKB Cases | Affected siblings, and second degree relative with confirmed mutation | Affected siblings, and second degree relative with confirmed mutation | Affected siblings, and second degree relative with confirmed mutation | Affected second degree relatives | Affected half sibling and distant relative | Affected half sibling and distant relative |
| Age at Clinical Presentation | Unknown | 3 months | 2 weeks | 2.5 months | 1 month | 3.5 months |
| Major Infections at Presentation and Before HCT* | Disseminated BCG* | Bacteremia (Klebsiella pneumoniae, E. Coli)* Otitis Media (E. Coli) Pyelonephritis (E.Coli) Pneumonia* (polymicrobial gram negatives) Candida albicans (oropharyngeal, perineum) Tinea capitis |
Bacteremia (E. Coli – recurrent) Thrush Recurrent pneumonias (undocumented pathogens) Disseminated HSV |
Disseminated BCG* Disseminated CMV (lungs, blood, urine)* Disseminated Adenovirus (lungs, urine)* Bacteremia (Streptococcus pneumoniae, Stenotrophomonas maltophilia) |
Disseminated BCG* Disseminated CMV (lungs, brain, blood, adrenal glands, heart)* Candida albicans (oropharyngeal, meningitis)* Bacteremia (E. Coli, Morganella morganni, Staphylococcus aureus) Meningitis (Staphylococcus aureus) Varicella zoster virus |
Disseminated Adenovirus (nasal, stool, urine)* Disseminated CMV (Blood) * Bacteremia (E. Coli, Pseudomonas aeruginosa) Thrush |
| Died Before HCT | Yes | Yes | No | No | Yes | No |
| Received HCT | No. HCT not available at the time | No. HCT not available at the time | Yes | Yes | No. Multi-organ failure present. Not HCT candidate. | Yes. Two maternal HLA 10/10 identical bone marrow transplants. |
| Died After HCT | N/A | N/A | Yes | Yes (Day +9) | N/A | Yes (Day +122) |
| Age at Death | Infant (<4 months) | 14 months | 7 years | 4 months | 5 months | 8 months |
| Patient | 7** | 8** | 9 | 10** | 11 |
|---|---|---|---|---|---|
| Decade of Diagnosis | 2000s | 2000s | 2000s | 2010s | 2010s |
| IKBKB Mutation Confirmed | Yes | Yes | No | Yes | Yes |
| Direct Family Relationships to Known IKBKB Cases | None | None | Affected siblings with confirmed mutations | Affected siblings | Affected siblings |
| Age at Clinical Presentation | 2 months | 1 month | 1 month | 3 months | 2 months |
| Major Infections at Presentation and Before HCT* |
Listeria monocytogenes bacteremia and meningitis * Thrush |
Bacteremia (E. Coli) Pneumonia syndrome ND Thrush |
Pneumonia (RSV)* Bacteremia (Staphylococcus aureus, Enterococcus faecalis, Enterococcus faecium, Leuconostoc lactic) Meningitis (Enterococcus species)* Candida albicans (oropharyngeal, perineum) |
Bacteremia (Staphylococcus hominis, Enterococcus faecium) Thrush Pneumonia (Parainfluenza, Mycoplasma pneumoniae) |
Pneumonia (Rhinovirus)* Klebseilla pneumoniae bacteremia, pneumonia and meningitis* Thrush Scabies |
| Died Before HCT | Yes | No | Yes | No | Yes |
| Received HCT | No. Multi-organ failure present. Not HCT candidate. | Yes | No. SCID was suspected but since IKBKB mutation had not yet been described diagnosis was never confirmed. | Yes | No. Multi-organ failure present. Not HCT candidate. |
| Died After HCT | N/A | Yes (2 years) | N/A | No – Alive 7 years post-HCT | N/A |
| Age at Death | 2 months | 2 years | 15 months | N/A | 2.5 months |
| Patient | 12** | 13 | 14 | 15 | 16 |
|---|---|---|---|---|---|
| Decade of Diagnosis | 2010s | 1980s | 1990s | 2010s | 2010s |
| IKBKB Mutation Confirmed | Yes | No | Yes | Yes (NBS) | Yes (in-utero and post-natal) |
| Direct Family Relationships to Known IKBKB Cases | No | Affected sibling with confirmed mutation | Affected sibling | Affected sibling | Affected sibling |
| Age at Clinical Presentation | 3 months | 4 months | 2.5 months | 0 months - Newborn Screening | 0 months – Family History |
| Major Infections at Presentation and Before HCT* | Serratia marcescens bacteremia and intracerebral abscesses. Bacteremia (E. Coli, Klebsiella pneumoniae) Candida albicans (oropharyngeal, urine) Pneumonia (RSV, coronavirus) Hemophagocytic Lymphohistiocytosis |
“Sepsis”* | Disseminated BCG* (including M. bovis meningitis and intracerebral abscesses) Fungemia (Candida albicans)* Bacteremia (Stenotrophomonas maltophilia, Enterobacter cloacae, E. Coli) |
None | None |
| Died Before HCT | No | Yes | Yes | No | No |
| Received HCT | Yes | No. HCT not available at the time. | No. Multi-organ failure present. Not HCT candidate. | Yes | Yes |
| Died After HCT | No – Alive 6 years post-HCT | N/A | N/A | Yes | No – Alive 6-months post-HCT |
| Age at Death | N/A | 4.5 months | 3.5 months | 11 months | N/A |
*Single asterisks refer to infections that ultimately resulted in death due to multi-organ failure and / or severe neurological injury. Involvement of organs was confirmed at the time of autopsy.
**Double asterisks refer to patients included in the original publication (Pannicke et al, reference 1).
Abbreviations: BCG: bacillus Calmette-Guerin; CMV: Cytomegalovirus; HCT: Hematopoietic Cell Transplantation; HLA: Human Leukocyte Antigen; HSV: Herpes Simplex Virus; HPV: Human Papilloma Virus; NBS: Newborn Screening; N/A: Not Applicable or Available; ND: Not Documented (infectious pathogen); RSV: Respiratory Syncytial Virus.