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C1Q deficiency 2(C1QD2)

MedGen UID:
1841058
Concept ID:
C5830422
Disease or Syndrome
Synonyms: C1Q DEFICIENCY 2; C1q DEFICIENCY 2; C1QD2
 
Gene (location): C1QB (1p36.12)
 
Monarch Initiative: MONDO:0958187
OMIM®: 620321

Definition

C1q deficiency (C1QD) is a rare autosomal recessive disorder characterized by recurrent skin lesions, chronic infections, and an increased risk of autoimmune diseases, particularly systemic lupus erythematosus (SLE; see 152700) or SLE-like diseases. It has also been associated with chronic glomerulonephritis and renal failure. C1q deficiency presents in 2 different forms, absent C1q protein or presence of a dysfunctional molecule (summary by Topaloglu et al., 1996 and Vassallo et al., 2007). For a discussion of genetic heterogeneity of C1q deficiency, see 613652. [from OMIM]

Clinical features

From HPO
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Vasculitis in the skin
MedGen UID:
488809
Concept ID:
C0262988
Disease or Syndrome
A type of vasculitis (inflammation of blood vessel walls) that affects skeletal muscle tissue.
Anemia
MedGen UID:
1526
Concept ID:
C0002871
Disease or Syndrome
A reduction in erythrocytes volume or hemoglobin concentration.
Arthritis
MedGen UID:
2043
Concept ID:
C0003864
Disease or Syndrome
Inflammation of a joint.
Atelectasis
MedGen UID:
13946
Concept ID:
C0004144
Pathologic Function
Collapse of part of a lung associated with absence of inflation (air) of that part.
Bronchiectasis
MedGen UID:
14234
Concept ID:
C0006267
Disease or Syndrome
Persistent abnormal dilatation of the bronchi owing to localized and irreversible destruction and widening of the large airways.
Recurrent lower respiratory tract infections
MedGen UID:
756211
Concept ID:
C3163798
Disease or Syndrome
An increased susceptibility to lower respiratory tract infections as manifested by a history of recurrent lower respiratory tract infections.
Chilblains
MedGen UID:
886
Concept ID:
C0008058
Injury or Poisoning
Chilblains, also called perniosis, are an inflammatory skin condition related to an abnormal vascular response to the cold. We are unaware of a reliable estimate of incidence. It typically presents as tender, pruritic red or bluish lesions located symmetrically on the dorsal aspect of the fingers, toes, ears and nose. Less commonly, reports describe involvement of the thighs and buttocks. The lesions present hours after exposure to cold and usually resolve spontaneously in one to three weeks.
Sepsis
MedGen UID:
48626
Concept ID:
C0036690
Disease or Syndrome
Systemic inflammatory response to infection.
Rheumatoid factor positive
MedGen UID:
56226
Concept ID:
C0151379
Laboratory or Test Result
The presence in the serum of an autoantibody directed against the Fc portion of IgG.
Antinuclear antibody positivity
MedGen UID:
101792
Concept ID:
C0151480
Laboratory or Test Result
The presence of autoantibodies in the serum that react against nuclei or nuclear components.
Malar rash
MedGen UID:
75808
Concept ID:
C0277942
Finding
An erythematous (red), flat facial rash that affects the skin in the malar area (over the cheekbones) and extends over the bridge of the nose.
Recurrent otitis media
MedGen UID:
155436
Concept ID:
C0747085
Disease or Syndrome
Increased susceptibility to otitis media, as manifested by recurrent episodes of otitis media.
Reduced circulating CH50 activity
MedGen UID:
1380457
Concept ID:
C4476774
Finding
A diminished activity of the classical complement pathway as measured by the assay for 50% haemolytic complement (CH50) activity of serum.
Anti-Sm antibody positivity
MedGen UID:
1755112
Concept ID:
C5421567
Finding
The presence of autoantibodies in the serum that react to seven proteins that consist of a core of small nuclear ribonucleoprotein (snRNP) particles.
Extractable nuclear antigen positivity
MedGen UID:
1785652
Concept ID:
C5539626
Laboratory or Test Result
The presence of autoantibodies in the serum that react against extractable nuclear components that are referred to as extractable because they can be extracted from cell nuclei with saline solution.
Discoid lupus erythematosus
MedGen UID:
1811126
Concept ID:
C5574816
Disease or Syndrome
Cutaneous lesion that develops as a dry, scaly, red patch that evolves to an indurated and hyperpigmented plaque with adherent scale. Scarring may result in central white patches (loss of pigmentation) and skin atrophy.
Decreased circulating C1q concentration
MedGen UID:
1841603
Concept ID:
C5826513
Finding
Concentration or activity of the C1q protein in the blood circulation below the lower limit of normal. C1q is the first component of the classical pathway and is composed of the C1qA chain, C1qB chain, and C1qC chain, which are encoded by C1qA, C1qB, and C1qC genes.
Pneumocystis carinii pneumonia
MedGen UID:
994080
Concept ID:
CN315554
Finding
Pneumocystis carinii pneumonia is an opportunistic infection that occurs in immunosuppressed populations.
Elevated erythrocyte sedimentation rate
MedGen UID:
57727
Concept ID:
C0151632
Finding
An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen.
Persistent fever
MedGen UID:
1720688
Concept ID:
C0476474
Pathologic Function
Fever that persists longer than expected for an acute infectious disease. No precise threshold exists, and the clinical interpretation of fever is context-dependent, but as a rule of thumb, this term refers to fever that persists longer than 2-3 weeks.
Elevated circulating C-reactive protein concentration
MedGen UID:
892906
Concept ID:
C4023452
Finding
An abnormal elevation of the C-reactive protein level in the blood circulation.
Oral ulcer
MedGen UID:
57699
Concept ID:
C0149745
Disease or Syndrome
Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.
Facial erythema
MedGen UID:
65986
Concept ID:
C0239488
Finding
Redness of the skin of the face, caused by hyperemia of the capillaries in the lower layers of the skin.

Professional guidelines

PubMed

Jachiet M, Flageul B, Deroux A, Le Quellec A, Maurier F, Cordoliani F, Godmer P, Abasq C, Astudillo L, Belenotti P, Bessis D, Bigot A, Doutre MS, Ebbo M, Guichard I, Hachulla E, Héron E, Jeudy G, Jourde-Chiche N, Jullien D, Lavigne C, Machet L, Macher MA, Martel C, Melboucy-Belkhir S, Morice C, Petit A, Simorre B, Zenone T, Bouillet L, Bagot M, Frémeaux-Bacchi V, Guillevin L, Mouthon L, Dupin N, Aractingi S, Terrier B; French Vasculitis Study Group
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Med Arh 2010;64(2):75-9. PMID: 20514769

Recent clinical studies

Etiology

Triaille C, Rao NM, Rice GI, Seabra L, Sutherland FJH, Bondet V, Duffy D, Gennery AR, Fournier B, Bader-Meunier B, Troedson C, Cleary G, Buso H, Dalby-Payne J, Ranade P, Jansen K, De Somer L, Frémond ML, Chavan PP, Wong M, Dale RC, Wouters C, Quartier P, Khubchandani R, Crow YJ
J Clin Immunol 2024 Aug 28;44(8):185. doi: 10.1007/s10875-024-01788-5. PMID: 39196411Free PMC Article
Thomas S, Smatti MK, Ouhtit A, Cyprian FS, Almaslamani MA, Thani AA, Yassine HM
Mol Immunol 2022 Dec;152:172-182. Epub 2022 Nov 10 doi: 10.1016/j.molimm.2022.11.010. PMID: 36371813Free PMC Article
Valle SOR, Alonso MLO, Dortas Junior SD, Goudouris ES, de Carvalho ALRB, Capelo AV, Mansour E, Bernardes AF, Leite LFB, Giavina-Bianchi P, Aun MV, Ferriani MPL, Arruda LK, Grumach AS
Int Arch Allergy Immunol 2022;183(5):572-577. Epub 2022 Mar 24 doi: 10.1159/000521646. PMID: 35325890
Proper SP, Lavery WJ, Bernstein JA
Allergy Asthma Proc 2020 Nov 1;41(Suppl 1):S03-S07. doi: 10.2500/aap.2020.41.200040. PMID: 33109317
Leffler J, Bengtsson AA, Blom AM
Ann Rheum Dis 2014 Sep;73(9):1601-6. Epub 2014 May 20 doi: 10.1136/annrheumdis-2014-205287. PMID: 24845390

Diagnosis

McMurray JC, Schornack BJ, Weskamp AL, Park KJ, Pollock JD, Day WG, Brockshus AT, Beakes DE, Schwartz DJ, Mikita CP, Pittman LM
Allergy Asthma Proc 2024 Sep 1;45(5):305-309. doi: 10.2500/aap.2024.45.240050. PMID: 39294906Free PMC Article
Miyata T, Horiuchi T
Allergol Int 2023 Jul;72(3):375-384. Epub 2023 May 9 doi: 10.1016/j.alit.2023.04.004. PMID: 37169642
Proper SP, Lavery WJ, Bernstein JA
Allergy Asthma Proc 2020 Nov 1;41(Suppl 1):S03-S07. doi: 10.2500/aap.2020.41.200040. PMID: 33109317
Patel G, Pongracic JA
Allergy Asthma Proc 2019 Nov 1;40(6):441-445. doi: 10.2500/aap.2019.40.4267. PMID: 31690390
Farkas H, Veszeli N, Kajdácsi E, Cervenak L, Varga L
Clin Rev Allergy Immunol 2016 Oct;51(2):140-51. doi: 10.1007/s12016-016-8539-6. PMID: 27142368

Therapy

Wang H, Tao L, Cui L, Chen Y, Liu D, Xue L, Yang Y, Lv Y, Zhang F, Wang T, Wang X, Yuan W, Liu H, Huang J, Jiang Y, Liu N, Yang L, Hu Y, Li Y, Gao Y, Li H, Li B, Song C
Sci Rep 2024 Sep 3;14(1):20519. doi: 10.1038/s41598-024-66267-8. PMID: 39227626Free PMC Article
Valle SOR, Alonso MLO, Dortas Junior SD, Goudouris ES, de Carvalho ALRB, Capelo AV, Mansour E, Bernardes AF, Leite LFB, Giavina-Bianchi P, Aun MV, Ferriani MPL, Arruda LK, Grumach AS
Int Arch Allergy Immunol 2022;183(5):572-577. Epub 2022 Mar 24 doi: 10.1159/000521646. PMID: 35325890
Nabavi M, Bahrami S, Arshi S, Rezaeifar A, Bemanian MH, Fallahpour M, Shokri S, Tehrani H
Iran J Allergy Asthma Immunol 2021 Feb 11;20(1):120-124. doi: 10.18502/ijaai.v20i1.5419. PMID: 33639628
Bordron A, Bagacean C, Tempescul A, Berthou C, Bettacchioli E, Hillion S, Renaudineau Y
Clin Rev Allergy Immunol 2020 Apr;58(2):155-171. doi: 10.1007/s12016-019-08741-0. PMID: 31144209
Markovic SN, Inwards DJ, Frigas EA, Phyliky RP
Ann Intern Med 2000 Jan 18;132(2):144-50. doi: 10.7326/0003-4819-132-2-200001180-00009. PMID: 10644276

Prognosis

Thomas S, Smatti MK, Ouhtit A, Cyprian FS, Almaslamani MA, Thani AA, Yassine HM
Mol Immunol 2022 Dec;152:172-182. Epub 2022 Nov 10 doi: 10.1016/j.molimm.2022.11.010. PMID: 36371813Free PMC Article
Magrini E, Di Marco S, Mapelli SN, Perucchini C, Pasqualini F, Donato A, Guevara Lopez ML, Carriero R, Ponzetta A, Colombo P, Cananzi F, Supino D, Reis ES, Peano C, Inforzato A, Jaillon S, Doni A, Lambris JD, Mantovani A, Garlanda C
Nat Cancer 2021 Feb;2(2):218-232. Epub 2021 Feb 18 doi: 10.1038/s43018-021-00173-0. PMID: 34505065Free PMC Article
Farkas H, Veszeli N, Kajdácsi E, Cervenak L, Varga L
Clin Rev Allergy Immunol 2016 Oct;51(2):140-51. doi: 10.1007/s12016-016-8539-6. PMID: 27142368
Cicardi M, Zingale LC, Pappalardo E, Folcioni A, Agostoni A
Medicine (Baltimore) 2003 Jul;82(4):274-81. doi: 10.1097/01.md.0000085055.63483.09. PMID: 12861105
Dalmasso AP
Crit Rev Clin Lab Sci 1986;24(2):123-83. doi: 10.3109/10408368609110272. PMID: 2971510

Clinical prediction guides

Triaille C, Rao NM, Rice GI, Seabra L, Sutherland FJH, Bondet V, Duffy D, Gennery AR, Fournier B, Bader-Meunier B, Troedson C, Cleary G, Buso H, Dalby-Payne J, Ranade P, Jansen K, De Somer L, Frémond ML, Chavan PP, Wong M, Dale RC, Wouters C, Quartier P, Khubchandani R, Crow YJ
J Clin Immunol 2024 Aug 28;44(8):185. doi: 10.1007/s10875-024-01788-5. PMID: 39196411Free PMC Article
Miyata T, Horiuchi T
Allergol Int 2023 Jul;72(3):375-384. Epub 2023 May 9 doi: 10.1016/j.alit.2023.04.004. PMID: 37169642
Thomas S, Smatti MK, Ouhtit A, Cyprian FS, Almaslamani MA, Thani AA, Yassine HM
Mol Immunol 2022 Dec;152:172-182. Epub 2022 Nov 10 doi: 10.1016/j.molimm.2022.11.010. PMID: 36371813Free PMC Article
Magrini E, Di Marco S, Mapelli SN, Perucchini C, Pasqualini F, Donato A, Guevara Lopez ML, Carriero R, Ponzetta A, Colombo P, Cananzi F, Supino D, Reis ES, Peano C, Inforzato A, Jaillon S, Doni A, Lambris JD, Mantovani A, Garlanda C
Nat Cancer 2021 Feb;2(2):218-232. Epub 2021 Feb 18 doi: 10.1038/s43018-021-00173-0. PMID: 34505065Free PMC Article
Mészáros T, Füst G, Farkas H, Jakab L, Temesszentandrási G, Nagy G, Kiss E, Gergely P, Zeher M, Griger Z, Czirják L, Hóbor R, Haris A, Polner K, Varga L
Lupus 2010 Apr;19(5):634-8. Epub 2010 Jan 13 doi: 10.1177/0961203309357059. PMID: 20071476

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