Table 8.
Complement deficiencies
| Disease | Genetic defect; presumed pathogenesis OMIM gene |
Inheritance | Laboratory features | Associated Features | Phenotype OMIM number |
|---|---|---|---|---|---|
| 1) Integral complement cascade component deficiencies | |||||
| C1q deficiency |
C1QA,: Classical complement pathway component 120550 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway Diminished clearance of apoptotic cells |
SLE, infections with encapsulated organisms | 613652 |
| C1q deficiency |
C1QB: Classical complement pathway component 120570 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway Diminished clearance of apoptotic cells |
SLE, infections with encapsulated organisms | 613652 |
| C1q deficiency |
C1QC: Classical complement pathway component 120575 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway Diminished clearance of apoptotic cells |
SLE, infections with encapsulated organisms | 613652 |
| C1r deficiency |
C1R: Classical complement pathway component 613785 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway | SLE, infections with encapsulated organisms | 216950 |
| C1s deficiency |
C1S: Classical complement pathway component 120580 |
AR | Absent CH50 hemolytic activity Defective activation of the classical pathway |
SLE, infections with encapsulated organisms | 613783 |
| C4 deficiency |
C4A, Classical complement pathway components 120810 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway Complete deficiency requires biallelic mutations/deletions/conversions of both C4A and C4B |
SLE, infections with encapsulated organisms | 614380 |
| C4 deficiency |
C4B: Classical complement pathway components 120820 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway Complete deficiency requires biallelic mutations/deletions/conversions of both C4A and C4B |
SLE, infections with encapsulated organisms | 614379 |
| C2 deficiency |
C2: Classical complement pathway component 217000 |
AR | Absent CH50 hemolytic activity, Defective activation of the classical pathway | SLE, infections with encapsulated organisms, atherosclerosis | 613927 |
| C3 deficiency LOF |
C3: Central complement component 120700 |
AR | Absent CH50 and AH50 hemolytic activity Defective opsonization Defective humoral immune response |
Infections; glomerulonephritis; Atypical Hemolytic-uremic syndrome with gain-of-function mutations. |
613779 |
| C3 GOF |
C3: Central complement component 120700 |
Gain-of-function AD | Increased activation of complement | Atypical Hemolytic-uremic syndrome | 612925 |
| C5 deficiency |
C5: Terminal complement component 120900 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 609536 |
| C6 deficiency |
C6: Terminal complement component 217050 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 612446 |
| C7 deficiency |
C7: Terminal complement component 217070 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 610102 |
| C8 αdeficiency |
C8A: Terminal complement component 120950 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 613790 |
| C8γ deficiency |
C8G: Terminal complement component 120930 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 613790 |
| C8β deficiency |
C8B: Terminal complement component 120960 |
AR | Absent CH50 and AH50 hemolytic activity Defective bactericidal activity |
Neisserial infections | 613789 |
| C9 deficiency |
C9: Terminal complement component 120940 |
AR | Reduced CH50 and AP50 hemolytic activity Deficient bactericidal activity |
Mild susceptibility to Neisserial infections | 613825 |
| MASP2 deficiency |
MASP2: Cleavage of C4 605102 |
AR | Deficient activation of the lectin activation pathway | Pyogenic infections; Inflammatory lung disease, autoimmunity |
613791 |
| Ficolin 3 deficiency |
FCN3: Activates the classical complement pathway 604973 |
AR | Absence of complement activation by the Ficolin 3 pathway. | Respiratory infections, abscesses | 613860 |
| 2) Complement Regulatory defects | |||||
| C1 inhibitor deficiency |
SERPING1: regulation of kinins and complement activation 606860 |
AD | Spontaneous activation of the complement pathway with consumption of C4/C2 Spontaneous activation of the contact system with generation of bradykinin from high molecular weight kininogen |
Hereditary angioedema | 106100 |
| Factor B |
CFB: Activation of the alternative pathway 138470 |
AD | Gain-of-function mutation with increased spontaneous AH50 | aHUS | 612924 |
| Factor D deficiency |
CFD: Regulation of the alternative complement pathway 134350 |
AR | Absent AH50 hemolytic activity | Neisserial infections | 613912 |
| Properdin deficiency |
CFP: Regulation of the alternative complement pathway 300383 |
XL | Absent AH50 hemolytic activity | Neisserial infections | 312060 |
| Factor I deficiency |
CFI: Regulation of the alternative complement pathway 217030 |
AR | Spontaneous activation of the alternative complement pathway with consumption of C3 | Infections, Neisserial infections, aHUS, preeclampsia | 610984 612923 |
| Factor H deficiency |
CFH: Regulation of the alternative complement pathway 134370 |
AR/AD | Spontaneous activation of the alternative complement pathway with consumption of C3 | Infections, Neisserial infections, aHUS, preeclampsia | 609814 235400 |
| Factor H –related protein deficiencies |
CFHR1-5: Bind C3b 134371 600889 605336 605337 608593 |
AR/AD | Normal CH50, AH50, autoantibodies to Factor H. Linked deletions of one or more CFHR genes leads to susceptibility autoantibody-mediated aHUS | aHUS, Neisserial infections | 235400 |
| Thrombomodulin |
THBD: Regulates complement and coagulant activation 188040 |
AD | Normal CH50, AH50 | aHUS | 612926 |
| Complement Receptor 3 (CR3) deficiency |
ITGAM
120980 |
AR | CR3 expression is lost in LAD1. See LAD1 in Table 5 | Infections | 609939 |
| Membrane Cofactor Protein (CD46) deficiency |
CD46: Dissociates C3b and C4b 120920 |
AD | Inhibitor of complement alternate pathway, decreased C3b binding | aHUS, infections, preeclampsia | 612922 |
| Membrane Attack Complex Inhibitor (CD59) deficiency |
CD59: Regulates the membrane attack complex formation 107271 |
AR | Erythrocytes highly susceptible to complement-mediated lysis | Hemolytic anemia, polyneuropathy | 612300 |