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Factor I deficiency(CFID)

MedGen UID:
483045
Concept ID:
C3463916
Disease or Syndrome
Synonyms: CFID; Complement factor I deficiency
SNOMED CT: Factor I deficiency (234621005); Complement factor 3i deficiency (234621005); Complement component 3 inactivator deficiency (234621005)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CFI (4q25)
 
Monarch Initiative: MONDO:0012594
OMIM®: 610984
Orphanet: ORPHA200418

Disease characteristics

Excerpted from the GeneReview: C3 Glomerulopathy
C3 glomerulopathy (C3G) is a complex ultra-rare complement-mediated renal disease caused by uncontrolled activation of the complement alternative pathway (AP) in the fluid phase (as opposed to cell surface) that is rarely inherited in a simple mendelian fashion. C3G affects individuals of all ages, with a median age at diagnosis of 23 years. Individuals with C3G typically present with hematuria, proteinuria, hematuria and proteinuria, acute nephritic syndrome or nephrotic syndrome, and low levels of the complement component C3. Spontaneous remission of C3G is uncommon, and about half of affected individuals develop end-stage renal disease (ESRD) within ten years of diagnosis, occasionally developing the late comorbidity of impaired visual acuity. [from GeneReviews]
Authors:
Bertha Martín  |  Richard JH Smith   view full author information

Additional description

From OMIM
Hereditary deficiency of complement factor I (CFID) is associated with a propensity to pyogenic infection and usually follows an autosomal recessive pattern of inheritance (Vyse et al., 1996). A subset of patients with CFID develop a renal disease termed 'C3 glomerulopathy' (C3G2), which is characterized by glomerular deposition of C3 observed on renal biopsy. Affected individuals have hematuria and proteinuria with variable progression of renal dysfunction (summary by Servais et al., 2007). For a discussion of genetic heterogeneity of C3G, see C3G1 (609814), also known as complement factor H deficiency.  http://www.omim.org/entry/610984

Clinical features

From HPO
Recurrent urinary tract infections
MedGen UID:
120466
Concept ID:
C0262655
Disease or Syndrome
Repeated infections of the urinary tract.
Renal insufficiency
MedGen UID:
332529
Concept ID:
C1565489
Disease or Syndrome
A reduction in the level of performance of the kidneys in areas of function comprising the concentration of urine, removal of wastes, the maintenance of electrolyte balance, homeostasis of blood pressure, and calcium metabolism.
Vasculitis
MedGen UID:
12054
Concept ID:
C0042384
Disease or Syndrome
Inflammation of blood vessel.
Infective arthritis
MedGen UID:
13918
Concept ID:
C0003869
Disease or Syndrome
The inflammation of one or more joints caused by any infectious pathogen within the joint space. Symptoms include pain, stiffness, and decreased range of motion in the affected joint.
Recurrent sinusitis
MedGen UID:
107919
Concept ID:
C0581354
Disease or Syndrome
A recurrent form of sinusitis.
Glomerulonephritis
MedGen UID:
6616
Concept ID:
C0017658
Disease or Syndrome
Inflammation of the renal glomeruli.
Pyelonephritis
MedGen UID:
19590
Concept ID:
C0034186
Disease or Syndrome
An inflammation of the kidney involving the parenchyma of kidney, the renal pelvis and the kidney calices.
Recurrent meningitis
MedGen UID:
152879
Concept ID:
C0746495
Disease or Syndrome
An increased susceptibility to meningitis as manifested by a medical history of recurrent episodes of meningitis.
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.
Decreased circulating complement C3 concentration
MedGen UID:
332469
Concept ID:
C1837512
Finding
Concentration of the complement component C3 in the blood circulation below the lower limit of normal.
Recurrent skin infections
MedGen UID:
377848
Concept ID:
C1853193
Disease or Syndrome
Infections of the skin that happen multiple times.
Decreased circulating complement factor H concentration
MedGen UID:
409784
Concept ID:
C1969222
Finding
Concentration of the complement component factor H in the blood circulation below the lower limit of normal.
Decreased circulating complement factor I concentration
MedGen UID:
370868
Concept ID:
C1970257
Finding
Concentration of the complement component factor I in the blood circulation below the lower limit of normal.
Recurrent meningococcal disease
MedGen UID:
369692
Concept ID:
C1970263
Finding
Recurrent infections by Neisseria meningitidis (one of the most common causes of bacterial meningitis), which is also known as meningococcus.
Recurrent streptococcus pneumoniae infections
MedGen UID:
488989
Concept ID:
C2169794
Finding
Increased susceptibility to streptococcus pneumoniae infections as manifested by a history of recurrent infections by streptococcus pneumoniae.
Decreased circulating complement factor B concentration
MedGen UID:
867275
Concept ID:
C4021636
Finding
Concentration of the complement component factor B in the blood circulation below the lower limit of normal.
Recurrent Haemophilus influenzae infections
MedGen UID:
870747
Concept ID:
C4025204
Finding
Increased susceptibility to Haemophilus influenzae infections as manifested by recurrent episodes of infection by Haemophilus influenzae.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVFactor I deficiency

Professional guidelines

PubMed

Backeljauw PF, Andrews M, Bang P, Dalle Molle L, Deal CL, Harvey J, Langham S, Petriczko E, Polak M, Storr HL, Dattani MT
Orphanet J Rare Dis 2023 Oct 7;18(1):312. doi: 10.1186/s13023-023-02928-7. PMID: 37805563Free PMC Article
Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society
Horm Res Paediatr 2016;86(6):361-397. Epub 2016 Nov 25 doi: 10.1159/000452150. PMID: 27884013
Backeljauw P, Bang P, Clayton PE, Geffner M, Woods KA
Pediatr Endocrinol Rev 2010 Feb;7 Suppl 1:154-71. PMID: 20463651

Recent clinical studies

Etiology

Backeljauw PF, Andrews M, Bang P, Dalle Molle L, Deal CL, Harvey J, Langham S, Petriczko E, Polak M, Storr HL, Dattani MT
Orphanet J Rare Dis 2023 Oct 7;18(1):312. doi: 10.1186/s13023-023-02928-7. PMID: 37805563Free PMC Article
Cao Z, Min J, Tan Q, Si K, Yang H, Xu C
Alzheimers Res Ther 2023 Aug 22;15(1):140. doi: 10.1186/s13195-023-01288-5. PMID: 37608387Free PMC Article
Storr HL, Chatterjee S, Metherell LA, Foley C, Rosenfeld RG, Backeljauw PF, Dauber A, Savage MO, Hwa V
Endocr Rev 2019 Apr 1;40(2):476-505. doi: 10.1210/er.2018-00146. PMID: 30265312Free PMC Article
Laron Z, Kauli R, Lapkina L, Werner H
Mutat Res Rev Mutat Res 2017 Apr-Jun;772:123-133. Epub 2016 Aug 5 doi: 10.1016/j.mrrev.2016.08.002. PMID: 28528685
Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society
Horm Res Paediatr 2016;86(6):361-397. Epub 2016 Nov 25 doi: 10.1159/000452150. PMID: 27884013

Diagnosis

Mastromauro C, Giannini C, Chiarelli F
Front Endocrinol (Lausanne) 2023;14:1141039. Epub 2023 Mar 15 doi: 10.3389/fendo.2023.1141039. PMID: 37008935Free PMC Article
Miller BS, Rogol AD, Rosenfeld RG
Horm Res Paediatr 2022;95(6):619-630. Epub 2022 Nov 29 doi: 10.1159/000527123. PMID: 36446332
Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society
Horm Res Paediatr 2016;86(6):361-397. Epub 2016 Nov 25 doi: 10.1159/000452150. PMID: 27884013
Argente J
Horm Res Paediatr 2016;85(1):2-10. Epub 2015 Dec 10 doi: 10.1159/000442350. PMID: 26649429
Growth Hormone Research Society
J Clin Endocrinol Metab 2000 Nov;85(11):3990-3. doi: 10.1210/jcem.85.11.6984. PMID: 11095419

Therapy

Miller BS, Rogol AD, Rosenfeld RG
Horm Res Paediatr 2022;95(6):619-630. Epub 2022 Nov 29 doi: 10.1159/000527123. PMID: 36446332
Grimberg A, Allen DB
Curr Opin Pediatr 2017 Aug;29(4):466-471. doi: 10.1097/MOP.0000000000000505. PMID: 28525404Free PMC Article
Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB, Rossi WC, Feudtner C, Murad MH; Drug and Therapeutics Committee and Ethics Committee of the Pediatric Endocrine Society
Horm Res Paediatr 2016;86(6):361-397. Epub 2016 Nov 25 doi: 10.1159/000452150. PMID: 27884013
Hua Y, Sahashi K, Rigo F, Hung G, Horev G, Bennett CF, Krainer AR
Nature 2011 Oct 5;478(7367):123-6. doi: 10.1038/nature10485. PMID: 21979052Free PMC Article
Growth Hormone Research Society
J Clin Endocrinol Metab 2000 Nov;85(11):3990-3. doi: 10.1210/jcem.85.11.6984. PMID: 11095419

Prognosis

Backeljauw P
Growth Horm IGF Res 2020 Apr;51:22-26. Epub 2020 Jan 13 doi: 10.1016/j.ghir.2020.01.001. PMID: 31982729
Jlajla H, Dehman F, Jallouli M, Khedher R, Ayadi I, Zerzeri Y, Laadhar L, Sfar I, Mahfoudh A, Gorgi Y, Cheour E, Zouaghi K, Gargah T, Kallel Sellami M
Nephrology (Carlton) 2019 Mar;24(3):357-364. doi: 10.1111/nep.13217. PMID: 29292855
Yeap BB, Flicker L
J Am Med Dir Assoc 2014 May;15(5):326-33. Epub 2014 Feb 12 doi: 10.1016/j.jamda.2013.12.004. PMID: 24529874
Mullis PE
Best Pract Res Clin Endocrinol Metab 2011 Feb;25(1):25-41. doi: 10.1016/j.beem.2010.06.006. PMID: 21396573
Backeljauw P, Bang P, Clayton PE, Geffner M, Woods KA
Pediatr Endocrinol Rev 2010 Feb;7 Suppl 1:154-71. PMID: 20463651

Clinical prediction guides

Backeljauw PF, Andrews M, Bang P, Dalle Molle L, Deal CL, Harvey J, Langham S, Petriczko E, Polak M, Storr HL, Dattani MT
Orphanet J Rare Dis 2023 Oct 7;18(1):312. doi: 10.1186/s13023-023-02928-7. PMID: 37805563Free PMC Article
Cao Z, Min J, Tan Q, Si K, Yang H, Xu C
Alzheimers Res Ther 2023 Aug 22;15(1):140. doi: 10.1186/s13195-023-01288-5. PMID: 37608387Free PMC Article
Steinman G
Med Hypotheses 2019 Jan;122:45-47. Epub 2018 Oct 22 doi: 10.1016/j.mehy.2018.10.015. PMID: 30593420
Yeap BB, Flicker L
J Am Med Dir Assoc 2014 May;15(5):326-33. Epub 2014 Feb 12 doi: 10.1016/j.jamda.2013.12.004. PMID: 24529874
Lombardi G, Tauchmanova L, Di Somma C, Musella T, Rota F, Savanelli MC, Colao A
J Endocrinol Invest 2005;28(10 Suppl):36-42. PMID: 16550721

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