Table 1.
Summary of clinical and immunological characteristics of published, genetically confirmed cases of CFI deficiency.
| Case | Age at first presentation (yr) | Family | Gender | Origin | Allele 1 | Allele 2 | Protein 1 | Protein 2 | Domain 1 | Domain 2 | Infections | Other manifestations | CFI | CFH | CFB | C3 | AP50 | CH50 | References | Notes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | 10 | 1 | F | British | c.191C>T | c.262C>A | p.P64L | p.Q88K | FIMAC | FIMAC | Recurrent haemorrhagic leukoencephalitis | Undetectable | n/a | n/a | 0.43 g/l | <50% | 876 (1,000–2,000) | This publication | ||
| 2 | n/a | 2 | F | Turkish | c.162C>G | Homozygous | p.C54W | Homozygous | FIMAC | FIMAC | Leukocytoclastic vasculitis | <5% | 47.00% | <3% | 0.29 g/L | 0.00% | 21.00% | (4) | ||
| 3 | 2 | 3 | M | Australian | c.133-134delAA | Homozygous | p.K45Sfs*11 | Homozygous | FIMAC | FIMAC | Recurrent infections with S. pneumoniae and S. pyogenes including septicaemia, joint infections and pneumonia | Juvenile idiopathic arthritis | Undetectable | 189 mg/L (345–590) | <38 mg/L (191–382) | 0.32 g/L (0.7–2.06) | Undetectable | 41.00% | (5) | |
| 4 | Childhood | 3 | M | Australian | c.133-134delAA | Homozygous | p.K45Sfs*11 | Homozygous | FIMAC | FIMAC | Otitis media | Undetectable | 148 mg/L (345–590) | <38 mg/L (191–382) | 0.22 g/L (0.7–2.06) | Undetectable | 11.00% | (5) | ||
| 5 | n/a | 4 | F | Spanish | c.80_81delAT | c.559C>T | p.D27Afs*18 | p.R187* | FIMAC | SRCR | Meningitis, penumonia | Henoch-Schonlein purpura | 0 | 9.4 mg/dl (12–56) | 0 mg/dL (7.5–28) | 38.4 | n/a | n/a | (6) | |
| 6 | 10 | 5 | F | Filipino | n/a | n/a | p.G71V | p.C196S | FIMAC | SRCR | Diffuse vasogenic cerebral oedema, neutrophilic brain infiltration | 4.6 mcg/ml (29–59) | 107 mcg/ml (160–412) | 43.8 mcg/ml (127.6–278.5) | 41 | <10% | 21 U/ml (30–75 U/ml) | (7) | Asymptomatic younger sister with same compound heterozygous mutations and complement profile | |
| 7 | 2 | 6 | F | Brazilian/Portuguese | c.129C>A | c.559C>T | p.C43* | p.R187* | FIMAC | SRCR | Spontaneous pneumococcal peritonitis | Undetectable | 211.0 mg/L (345–590) | 29.7 mg/L (295–400) | 21 mg/dL | 21.00% | 20.00% | This publication | ||
| 8 | 10 | 7 | M | Filipino | n/a | n/a | p.G71V | Heterozygote | FIMAC | Vasogenic cerebral oedema, neutrophilic cerebral inflammation | 6 mcg/ml (29–59) | 136 mcg/ml (160–412) | n/a | <40 | 29.00% | 40 U/ml (30–75 U/ml) | (7) | |||
| 9 | n/a | 8 | F | Spanish | c.559C>T | c1610_1611insAT | p.R187* | p.V537Vfs*2 | SRCR | SP | Pneumonia, facial cellulitis | Hypocomplementemic vasculitis | 4.00% | 4.8 mg/dl (12–56) | 0 mg/dL (7.5–28) | 31.5 | n/a | n/a | (6) | Asymptomatic younger sister with same compound heterozygous mutations and complement profile |
| 10 | 1 m | 9 | F | Denmark | c.563G>T | c.1253A>T | p.G188V | p.H418L | SRCR | SP | Recurrent bacterial upper respiratory tract infections, septicaemia, erysipelas | Undetectable | 64% (69–154) | <2.5% (59–154) | 48.00% | Reduced | Reduced | (8) | ||
| 11 | Childhood | 10 | M | Spanish | c.485G>A | Homozygous | p.G162D | Homozygous | SRCR | SRCR | Streptococcus bovis endocarditis, pneumonias, meningitis, sepsis | Undetectable | 26.3 mg/dl (12–56) | 4.5 mg/dL (20–40) | 29.6 | 0.00% | <12.1 U/ml | (9) | ||
| 12 | n/a | 11 | M | Spanish | c. 772 G>A | c. 772 G>A | p.D220-K257del | p.D220-K257del | LDRA1 | LDRA1 | Pneumonia, meningococcal septicaemia, oral thrush, balanitis | 0.00% | 8.40 mg/dl (12–56) | 0 mg/dL (7.5–28) | 22.6 | n/a | n/a | (6) | ||
| 13 | 16 | 12 | F | Spanish | c.739T>G | Homozygous | p.C247G | Homozygous | LDRA1 | LDRA1 | Recurrent meningitis coinciding with menstruation | n/a | 52 mcg/ml (200–600) | 6.7 mg/dL (17–60) | 24 mg/dl | n/a | <50 U/ml | (10, 11) | ||
| 14 | 18 | 12 | F | Spanish | c.739T>G | Homozygous | p.C247G | Homozygous | LDRA1 | LDRA1 | Meningitis, recurrent tonsillitis | 3.00% | 65 mcg/ml (200–600) | 7.3 mg/dl (17–60) | 22 mg/dl | n/a | <50 U/ml | (10, 11) | ||
| 15 | 2 | 13 | F | Spanish | c.772G>A | Homozygous | p.D220-K257del | Homozygous | LDRA1 | LDRA1 | Meningococcal meningitis, pneumococcal meningitis | Hyperpigmented skin lesions | n/a | 100 mcg/ml (200–600) | <12 md/dL (17–60) | 16.5 mg/dl | n/a | 140 U/ml (200–400 U/ml) | (10) | |
| 16 | 31 | 13 | M | Spanish | c.772G>A | Homozygous | p.D220-K257del | Homozygous | LDRA1 | LDRA1 | Lymphoid meningitis | Hyperpigmented skin lesions | n/a | 80 mcg/ml (200–600) | n/a | 24.7 mg/dl | n/a | 136 U/ml (200–400 U/ml) | (10) | |
| 17 | 9 | 13 | M | Spanish | c.772G>A | Homozygous | p.D220-K257del | Homozygous | LDRA1 | LDRA1 | Otitis, septic arthritis | Hyperpigmented skin lesions | n/a | 60 mcg/ml (200–600) | <12 md/dL (17–60) | 17.3 mg/dl | n/a | 142 U/ml (200–400 U/ml) | (10) | |
| 18 | 4 | 14 | F | Turkish | c.764G>A | Homozygous | p.C255Y | Homozygous | LDRA1 | LDRA1 | Recurrent upper and lower respiratory tract infections, meningitis | Recurrent vasculitic eruptions, immune complex glomerulonephritis, microscopic haematuria | Undetectable | 48% (69–154) | <12% (59–154) | 0.48 g/L (0.77–1.38) | Undetectable | Normal range | (8, 12) | 2 female siblings share genotype—disease manifestations not reported; 1 female sibling died of sepsis at 18 m but DNA was not available |
| 19 | n/a (diagnosed at 23) | 15 | F | Swedish | c.748C>A | c.803C>T | p.Q250K | p.S268K | LDRA1 | LDRA2 | Systemic lupus erythematosus | 2.00% | 85% (69–154) | 44% (59–154) | 63.00% | Reduced | Normal range | (8) | ||
| 20 | 10 | 16 | F | Croatia | c.772G>A | c.1100T>G | p.D220-K257del | p.I357M | LDRA1 | SP | Pneumonia, recurrent upper respiratory tract infections | Undetectable | 81% (69–154) | 13% (59–154) | 73.00% | Normal | Reduced | (8) | ||
| 21 | n/a (diagnosed at 18) | 17 | F | Turkish | c.866A>T | Homozygous | p.D289V | Homozygous | LDRA2 | LDRA2 | Recurrent upper and lower respiratory tract infections | Recurrent vasculitic eruptions and arthralgias | Undetectable | 65% (69–154) | ~10% (59–154) | 0.47 g/L (0.7–2.06) | Undetectable | 13.00% | (5) | |
| 22 | 5 | 18 | M | Spanish | c.1420 C>T | 5.6 kB gene deletion | p.R474* | - | SP | - | Meningitis with meningococcal septicaemia, otitis | 0.00% | 19.5 mg/dl (12–56) | 0 mg/dL (7.5–28) | 33.4 | n/a | n/a | (6) | Asymptomatic younger brother with same compound heterozygous mutations and complement profile | |
| 23 | 4 m | 19 | F | UK | c.1253A>T | c.772G>A | p.H418L | p.D220-K257del | SP | LDRA1 | Pneumococcal meningitis, recurrent meningococcal meningitis, otitis media | Undetectable | n/a | 10.00% | 30.00% | Undetectable | 14 U/ml (28–45 U/ml) | (13, 14) | ||
| 24 | 2 | 20 | F | Pakistani | c.1139A > G | Homozygous | p.H380R | Homozygous | SP | SP | Otitis media, lower respiratory tract infection | Cutaneous vasculitis, arthralgia | 36% (19 mg/L) | 219 mg/L (36%) | n/a | 22 | 0.00% | 5.00% | (15) | Asymptomatic older brother with same homozygous mutations and complement profile |
| 25 | 16 | 21 | F | Belgian | c. 1019 T>C | c. 1571 A>C | p.I340T | p.D524V | SP | SP | Aseptic meningoencephalitis, leukocutaneous vasculitis | 44 mg/L (25–44) | 460 mg/L (360–680) | 1 mg/dL (8–21) | 57 | 0.00% | 97.00% | (16) | ||
| 26 | 4 | 22 | F | Pakistani | c.1139A>G | Homozygous | p.H380R | Homozygous | SP | SP | Otitis media | Recurrent abdominal pain | 2.5 mg/dL | 35.5 mg/dl (12–56) | 1.2 mg/dL (20–40) | 35.2 | 0.00% | <12.1 U/ml | (9) | Asymptomatic younger brother with same homozygous mutation, absent factor I but normal C3 |
| 27 | 18 m | 23 | M | Scottish | c.1253A>T | Homozygous | p.H418L | Homozygous | SP | SP | Staphylococcus epidermidis septic arthritis, meningococcal meningitis, recurrent sinusitis, facial cellulitis | Undetectable | 46.00% | Undetectable | 28.00% | Undetectable | Undetectable | (13, 17) | Asymptomatic older sister with same homozygous mutation | |
| 28 | Childhood | 24 | M | Spanish | c.1450_1454delCTTCA | Homozygous | p.L484Vfs*3 | Homozygous | SP | SP | Otitis media, pharyngitis, invasive meningococcal infection, infected sacral cyst | Undetectable | 19.14 mg/dL (12–56) | 0.77 mg/dL (20.5–40) | 19.3 mg/dl | Undetectable | 2 UI/ml (34–71 UI/ml) | (18) | ||
| 29 | 15 m | 25 | F | Brazilian | c.1176insAT | Homozygous | p.W393Yfs*5 | Homozygous | SP | SP | Post-operative infection, bacterial meningitis, otitis, pneumonia | Henoch-Schonlein purpura and subsequent systemic lupus erythematosus: diffuse proliferative membranous glomerulonephritis, psychosis, seizures, stroke, photosensitive malar rash | Undetectable | 93 (454 ± 124 mcg/ml) | Undetectable | 127 ug/ml (1,300–1,500) | Undetectable | Undetectable | (19, 20) | |
| 30 | 3 | 25 | F | Brazilian | c.1176insAT | Homozygous | p.W393Yfs*5 | Homozygous | SP | SP | Adenoid hyperplasia, gastrointestinal infection progressing to fatal severe bilateral pneumonia | Undetectable | 105 (454 ± 124 mcg/ml) | Undetectable | 259 ug/ml (1,300–1,500) | Undetectable | Undetectable | (19, 20) | ||
| 31 | 3 m | 26 | F | Argentinian | c.1006C>T | Homozygous | p.Q354* | Homozygous | SP | SP | Otitis media, recurrent pneumonia | Recurrent vasculitis | Undetectable | 100% (69–154) | <12% (59–154) | 39.00% | Reduced | Reduced | (8) | |
| 32 | 4 | 27 | F | Spanish | c.1176_1177dupAT | c.485G>A | p.W393Yfs*5 | p.G162D | SP | SRCR | Otitis, sinusitis, bronchitis, meningococcal septicaemia | Arthritis | 2.00% | 8.23 mg/dl (12–56) | 0 mg/dL (7.5–28) | 22.8 | n/a | n/a | (6) |
FIMAC, factor I membrane attack complex; SRCR, scavenger receptor cysteine rich; SP, serine protease; LRDA, low density lipoprotein receptor class A domain.