Table 7.
Clinical and laboratory phenotype of human MALT1 deficiency (LOF MALT1 mutations).
| Mutation | p.Trp580Ser | p.Ser89Ile | p.Ser89Ile | c.[1019-2A>G];[1060delC] | p.Asp184Tyr | p.Asp184Tyr |
|---|---|---|---|---|---|---|
| Age | 15yo | 4yo | 2.25yo | 9–13 months | 7yo | 4yo |
| Sex | F | F | M | M | F | M |
| Ethnicity | Kurdish | Lebanese | Lebanese | American | ND | ND |
| Consanguinity | + | + | + | – | + | + |
| Functional Impact | Loss | Loss | Loss | Loss | Loss | Loss |
| Inheritance | AR | AR | AR | AD | AR | AR |
| Gene Expression | Normal | Normal | ND | Decreased/none | Normal | Normal |
| Protein Expression | ↓↓↓ | None | ND | None | None | None |
| INFECTIONS | ||||||
| Pulmonary | + | + | + | + | + | + |
| Staphylococcus aureus | + | – | + | – | – | – |
| Streptococcus pneumoniae | + | + | – | – | + | – |
| Haemophilus influenzae | – | – | + | – | – | – |
| Klebsiella pneumoniae | – | – | + | – | – | – |
| Pneumocystis jirovecii | – | – | – | – | + | – |
| Pseudomonas | – | + | – | – | – | – |
| CMV | + | – | – | + | + | – |
| EBV | – | – | – | – | + | – |
| RSV | – | – | – | + | – | – |
| Adenovirus | – | – | – | – | + | + |
| Candida albicans | – | + | – | – | – | – |
| Gastrointestinal | – | + | + | + | + | + |
| Salmonella | – | – | – | – | + | + |
| Campylobacter jejuni | – | – | – | – | + | – |
| Clostridium difficile | – | – | – | + | – | – |
| CMV | – | – | – | – | + | – |
| EBV | – | – | – | – | + | – |
| Rotavirus | – | – | – | – | + | – |
| Adenovirus | – | – | – | – | + | – |
| Candida albicans | – | – | + | – | – | – |
| Skin | + | – | – | + | + | + |
| Staphylococcus aureus | + | – | – | + | – | – |
| Pseudomonas | – | – | – | – | – | + |
| HSV-1 | + | – | – | – | + | + |
| VZV | + | – | – | – | – | – |
| Candida albicans | – | – | – | + | + | + |
| Blood | – | – | – | + | + | – |
| Staphylococcus aureus | – | – | – | – | + | – |
| Streptococcus pneumoniae | – | – | – | – | + | – |
| CMV | – | – | – | + | – | – |
| Urine | – | + | + | – | – | – |
| CMV | – | + | + | – | – | – |
| Meningitis | – | + | – | – | – | – |
| Haemophilus influenzae | – | + | – | – | – | – |
| Streptococcus pneumoniae | – | + | – | – | – | – |
| Keratitis | – | – | – | – | + | – |
| HSV-1 | – | – | – | – | + | – |
| CLINICAL MANIFESTATIONS | ||||||
| Failure to thrive | + | + | + | + | + | – |
| Dysmorphic facies | + | – | – | – | + | + |
| Periodontal disease | + | + | + | + | + | + |
| Eczema | + | – | – | + | + | + |
| Enteropathy | + | + | + | + | + | – |
| Bronchiectasis | + | + | + | – | + | – |
| THERAPY | ||||||
| Transplantation | + | – | – | + | + | + |
| Successful | + | N/A | N/A | + | + | + |
| IVIG | – | + | + | + | + | – |
| Anti-microbial prophylaxis | ND | ND | ND | + | + | + |
| Antibiotics | ND | ND | ND | + | + | + |
| TMP/SMX | ND | ND | ND | ND | + | + |
| ANTI-VIRAL | ||||||
| Gancyclovir | – | – | – | + | – | – |
| Foscarnet | – | – | – | + | + | + |
| Acyclovir | – | – | – | – | + | + |
| IMMUNOSUPPRESSION | ||||||
| Pre-transplantation | + | – | – | – | + | + |
| Treosulfan | – | – | – | – | – | – |
| Fludarabine | + | – | – | – | + | + |
| Busulfan | – | – | – | – | + | + |
| Alemtuzumab | + | – | – | – | + | + |
| Cyclophosphamide | – | – | – | + | – | – |
| Melphalan | – | – | – | + | – | – |
| R α-thymocyte globulin | – | – | – | + | – | – |
| Post-transplantation | + | – | – | + | + | + |
| Cyclosporine | + | – | – | + | + | + |
| Mycophenolate mofetil | + | – | – | – | + | + |
| Methylprednisone | + | – | – | – | – | – |
| Methotrexate | – | – | – | + | – | – |
| Tacrolimus | – | – | – | – | – | + |
| Outcome | Alive | Dead | Dead | Alive | Alive | Alive |
| Cause of death | N/A | Respiratory failure | Respiratory failure | N/A | N/A | N/A |
| LYMPHOCYTES | ||||||
| Total CD19 B cells | ↓ | Normal | ↓ | Normal | Normal | Normal |
| Naive | ↑ | ND | ND | ND | ND | ND |
| (Class-switched) memory | ↓ | ND | ND | ND | ND | ND |
| MZ | ↓ | ND | ND | ND | ND | ND |
| Total CD3 T cells | ↑ | Normal | Normal | ↑ | ↑ | ↑ |
| CD4 | ↑ | Normal | ↑ | ↑ | ↑ | ↑ |
| CD4 CD45RA | ND | Normal | Normal | Normal | Normal | ↑ |
| CD8 | ND | ↑ | Normal | ↑ | Normal | ↑ |
| CD8 CD45RA | ND | ND | ND | ↑ | ND | ND |
| Treg | Normal | ND | ND | ↓ | ↓ | ↓ |
| PROLIFERATION | ||||||
| PHA | ↓ | ↓ | ↓ | ↓ | ↑ | Normal |
| ConA | ND | ↓ | ↓ | ↓ | ND | ND |
| PWM | ND | ↓ | ↓ | Normal | ND | ND |
| CD3 | ND | ↓ | ↓ | ND | ND | ND |
| CD3+CD28 | ND | ND | ND | ND | ↓ | ↓ |
| Tetanus | ND | ↓ | ↓ | ND | ND | ND |
| Diphtheria | ND | ↓ | ↓ | ND | ND | ND |
| Candida | ND | ↓ | ↓ | ND | ND | ND |
| IMMUNOGLOBULINS | ||||||
| IgG | Normal | Normal | Normal | ↓ | Normal | Normal |
| IgA | Normal | Normal | Normal | Normal | Normal | Normal |
| IgM | Normal | Normal | Normal | ↓ | ↓ | ↓ |
| IgE | ↑ | Normal | Normal | Normal | ↑ | ↑ |
| Specific antibodies | ||||||
| Tetanus | Positive | Negative | Negative | Negative | ND | ND |
| Pneumococcal | ND | Negative | Negative | Negative | ND | ND |
| Diphtheria | Positive | ND | ND | Negative | ND | ND |
| Isohemagglutinins | Positive | Negative | Negative | ↓ | ND | ND |
| Haemophilus influenzae B | ND | ND | ND | Negative | ND | ND |
| References | (22) | (21) | (21) | (23) | (24) | (24) |
Summary of molecular, immunological, infectious, and pathological findings for all MALT1-deficient patients described to date. ND, no data; ↑, increased levels relative to normal range; ↓, decreased levels relative to normal range; +, present; −, absent; EBV, Epstein-Barr virus; HSV-1, herpes simplex encephalitis 1; VZV, varicella-zoster virus; R, rabbit.