Table 7.
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.