IFD
MCID: INT088
MIFTS: 34

Intrinsic Factor Deficiency (IFD)

Categories: Gastrointestinal diseases, Genetic diseases, Metabolic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Intrinsic Factor Deficiency

MalaCards integrated aliases for Intrinsic Factor Deficiency:

Name: Intrinsic Factor Deficiency 57 20 29 13 6 39 70
Ifd 57 20 72
Pernicious Anemia, Congenital, Due to Defect of Intrinsic Factor 57 20
Congenital Pernicious Anemia Due to Defect of Intrinsic Factor 20
Megaloblastic Anemia Due to Inborn Errors of Metabolism 70
Intrinsic Factor, Congenital Deficiency of 20
Congenital Deficiency of Intrinsic Factor 70
Congenital Intrinsic Factor Deficiency 20
Hereditary Intrinsic Factor Deficiency 72
Congenital Pernicious Anemia 72

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

Miscellaneous:
onset in childhood


HPO:

31
intrinsic factor deficiency:
Inheritance autosomal recessive inheritance
Onset and clinical course juvenile onset


Classifications:



External Ids:

OMIM® 57 261000
MedGen 41 C1394891
UMLS 70 C0340957 C1306856 C1394891

Summaries for Intrinsic Factor Deficiency

GARD : 20 Intrinsic factor deficiency is a rare condition that is characterized by pernicious anemia and neurological abnormalities. Most affected people develop signs and symptoms of the condition before age 5 years which may include failure to thrive and symptoms related to anemia (i.e. fatigue, pale skin, etc). Without early diagnosis and treatment, nervous system damage may occur which can be associated with confusion; depression; and numbness or tingling in the hands and/or feet. Intrinsic factor deficiency is caused by changes ( mutations ) in the GIF gene and is inherited in an autosomal recessive manner. Treatment generally consists of vitamin B12 injections.

MalaCards based summary : Intrinsic Factor Deficiency, also known as ifd, is related to pernicious anemia and congenital intrinsic factor deficiency. An important gene associated with Intrinsic Factor Deficiency is CBLIF (Cobalamin Binding Intrinsic Factor). Affiliated tissues include small intestine, bone marrow and bone, and related phenotypes are malabsorption and abnormality of the immune system

OMIM® : 57 Congenital pernicious anemia (PA), or intrinsic factor deficiency, is a rare disorder characterized by the lack of gastric intrinsic factor in the presence of normal acid secretion and mucosal cytology and the absence of GIF antibodies that are found in the acquired form of pernicious anemia (170900). See also pernicious anemia due to defect in the receptor for vitamin B12/intrinsic factor (261100). (261000) (Updated 05-Apr-2021)

UniProtKB/Swiss-Prot : 72 Hereditary intrinsic factor deficiency: Autosomal recessive disorder characterized by megaloblastic anemia.

Wikipedia : 73 Intrinsic factor (IF), also known as gastric intrinsic factor (GIF), is a glycoprotein produced by the... more...

Related Diseases for Intrinsic Factor Deficiency

Graphical network of the top 20 diseases related to Intrinsic Factor Deficiency:



Diseases related to Intrinsic Factor Deficiency

Symptoms & Phenotypes for Intrinsic Factor Deficiency

Human phenotypes related to Intrinsic Factor Deficiency:

31 (show all 10)
# Description HPO Frequency HPO Source Accession
1 malabsorption 31 HP:0002024
2 abnormality of the immune system 31 HP:0002715
3 paresthesia 31 HP:0003401
4 abnormality of metabolism/homeostasis 31 HP:0001939
5 sensory impairment 31 HP:0003474
6 megaloblastic anemia 31 HP:0001889
7 increased mean corpuscular volume 31 HP:0005518
8 megaloblastic erythroid hyperplasia 31 HP:0200143
9 malabsorption of vitamin b12 31 HP:0200118
10 absence of intrinsic factor 31 HP:0005219

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Peripheral Nervous System:
peripheral neuropathy
sensory impairment
paresthesias

Abdomen Gastrointestinal:
vitamin b12 deficiency caused by intestinal malabsorption
absence of intrinsic factor by immunoassay of gastric juices
normal gastric mucosa
normal gastric acid secretion
normal pepsin secretion

Laboratory Abnormalities:
decreased serum b12 levels

Hematology:
megaloblastic anemia
increased mean corpuscular volume
bone marrow biopsy shows megaloblastic erythroid hyperplasia

Immunology:
absence of auto-antibodies to intrinsic factor or parietal cells

Clinical features from OMIM®:

261000 (Updated 05-Apr-2021)

Drugs & Therapeutics for Intrinsic Factor Deficiency

Search Clinical Trials , NIH Clinical Center for Intrinsic Factor Deficiency

Genetic Tests for Intrinsic Factor Deficiency

Genetic tests related to Intrinsic Factor Deficiency:

# Genetic test Affiliating Genes
1 Intrinsic Factor Deficiency 29 CBLIF

Anatomical Context for Intrinsic Factor Deficiency

MalaCards organs/tissues related to Intrinsic Factor Deficiency:

40
Small Intestine, Bone Marrow, Bone, Brain

Publications for Intrinsic Factor Deficiency

Articles related to Intrinsic Factor Deficiency:

(show top 50) (show all 58)
# Title Authors PMID Year
1
Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency. 57 6 61
14576042 2004
2
Hereditary juvenile cobalamin deficiency caused by mutations in the intrinsic factor gene. 57 6
15738392 2005
3
Biochemical and Hematologic Manifestations of Gastric Intrinsic Factor (GIF) Deficiency: A Treatable Cause of B12 Deficiency in the Old Order Mennonite Population of Southwestern Ontario. 6 61
25308559 2015
4
How can cobalamin injections be spaced in long-term therapy for inborn errors of vitamin B(12) absorption? 61 6
22854512 2012
5
Inherited cobalamin malabsorption. Mutations in three genes reveal functional and ethnic patterns. 6 61
22929189 2012
6
A genetic polymorphism in the coding region of the gastric intrinsic factor gene (GIF) is associated with congenital intrinsic factor deficiency. 61 57
14695536 2004
7
Congenital intrinsic factor deficiency in a Spanish patient. 57 61
1581408 1992
8
Gastric juice in congenital pernicious anemia contains no immunoreactive intrinsic factor molecule: study of three kindreds with variable ages at presentation, including a patient first diagnosed in adulthood. 61 57
6823973 1983
9
Primary immunodeficiency diseases: Genomic approaches delineate heterogeneous Mendelian disorders. 6
27577878 2017
10
Vitamin B12 deficiency in a 15-year old boy due to mutations in the intrinsic factor gene, GIF. 6
20408840 2010
11
Juvenile cobalamin deficiency in individuals of African ancestry is caused by a founder mutation in the intrinsic factor gene GIF. 6
19036097 2009
12
The mouse homologs of human GIF, DDB1, and CFL1 genes are located on chromosome 19. 57
9530637 1998
13
Human gastric intrinsic factor: characterization of cDNA and genomic clones and localization to human chromosome 11. 57
2071148 1991
14
Cobalamin malabsorption in three siblings due to an abnormal intrinsic factor that is markedly susceptible to acid and proteolysis. 57
3908480 1985
15
Isolation and characterization of an abnormal human intrinsic factor. 57
4207620 1974
16
Vitamin B 12 malabsorption due to a biologically inert intrinsic factor. 57
5044916 1972
17
Congenital pernicious anemia: effects on growth, brain, and absorption of B12. 57
5657671 1968
18
Juvenile "congenital" pernicious anemia. Clinical and immunologic studies. 57
5922169 1966
19
PERNICIOUS ANEMIA IN CHILDHOOD. 57
14279251 1965
20
NOTES ON VITAMIN B12 ABSORPTION; AUTOIMMUNITY AND CHILDHOOD PERNICIOUS ANEMIA; RELATION OF INTRINSIC FACTOR TO BLOOD GROUP SUBSTANCE. 57
14226584 1964
21
Hereditary intrinsic factor deficiency in China caused by a novel mutation in the intrinsic factor gene-a case report. 61
33172407 2020
22
Autoimmune Gastritis. 61
31661309 2019
23
Vitamin B12 Deficiency in a Patient Presenting with Dyspnea: A Case Report. 61
31172130 2019
24
Frequency of intrinsic factor antibody in megaloblastic anaemia. 61
24613108 2014
25
Vitamin B12 absorption: mammalian physiology and acquired and inherited disorders. 61
23178706 2013
26
Gastric intrinsic factor deficiency with combined GIF heterozygous mutations and FUT2 secretor variant. 61
23402911 2013
27
Hereditary intrinsic factor deficiency in chaldeans. 61
23430489 2013
28
Diagnosis and management of pernicious anemia. 61
21947876 2011
29
Inborn errors of cobalamin absorption and metabolism. 61
21312325 2011
30
Pernicious anemia: new insights from a gastroenterological point of view. 61
19891010 2009
31
[Oral better than parenteral supplementation of vitamin B12]. 61
19900336 2009
32
[Hereditary juvenile cobalamin deficiency due to mutations in GIF gene]. 61
18620679 2008
33
Acquired and inherited disorders of cobalamin and folate in children. 61
16846473 2006
34
Nonradioactive vitamin B12 absorption test evaluated in controls and in patients with inherited malabsorption of vitamin B12. 61
16166166 2005
35
[Vitamin B12 deficiency. New data on an old theme]. 61
16395986 2005
36
Case of megaloblastic anemia caused by intestinal taeniasis. 61
14730392 2004
37
[Atrophic gastritis presenting with pulmonary embolism]. 61
11341183 2000
38
Genetic defects of folate and cobalamin metabolism. 61
9587028 1998
39
Primary gastric lymphoma presenting with vitamin B12 deficiency and achlorhydria. 61
8946996 1996
40
[Dementia caused by bacterial overgrowth in a patient with Billroth II gastrectomy]. 61
8755325 1996
41
[Imerslund-Najman-Grasbeck anemia. Apropos of a case]. 61
8015868 1993
42
Bound vitamin B12 absorption in patients with low serum B12 levels. 61
1609768 1992
43
One-step chromogenic equivalent of activated partial thromboplastin time evaluated for clinical application. 61
1855296 1991
44
[Congenital intrinsic factor deficiency. Apropos of 3 cases in a sibship]. 61
3395196 1988
45
Incidence and clinical significance of protein-bound vitamin B12 malabsorption. 61
3595808 1987
46
Malabsorption of vitamin B12 and intrinsic factor secretion during biguanide therapy. 61
6825978 1983
47
[Influence of intrinsic factor deficiency on malabsorption of vitamin B12 bound to proteins in achlorhydria]. 61
7117768 1982
48
Intrinsic factor deficiency in adults with normal hydrochloric acid production. 61
7450447 1981
49
[Vitamins in metabolic diseases]. 61
7027768 1981
50
[Juvenile pernicious anemia with congenital intrinsic factor deficiency and intermediate intrinsic factor secretion in the parents]. 61
711491 1978

Variations for Intrinsic Factor Deficiency

ClinVar genetic disease variations for Intrinsic Factor Deficiency:

6 (show top 50) (show all 56)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 CBLIF NM_005142.3(CBLIF):c.161del (p.Asn54fs) Deletion Pathogenic 1747 rs1590860794 GRCh37: 11:59611447-59611447
GRCh38: 11:59843974-59843974
2 CBLIF NM_005142.3(CBLIF):c.1175dup (p.Thr393fs) Duplication Pathogenic 1748 rs1590854624 GRCh37: 11:59599167-59599168
GRCh38: 11:59831694-59831695
3 CBLIF NM_005142.3(CBLIF):c.80-1G>A SNV Pathogenic 1745 rs1590860877 GRCh37: 11:59611529-59611529
GRCh38: 11:59844056-59844056
4 CBLIF NM_005142.3(CBLIF):c.183_186del (p.Met61fs) Deletion Pathogenic 566919 rs765896727 GRCh37: 11:59611422-59611425
GRCh38: 11:59843949-59843952
5 CBLIF NM_005142.3(CBLIF):c.79+1G>A SNV Pathogenic 439755 rs147785187 GRCh37: 11:59612847-59612847
GRCh38: 11:59845374-59845374
6 CBLIF NM_005142.3(CBLIF):c.661G>A (p.Gly221Arg) SNV Likely pathogenic 830018 rs1590859406 GRCh37: 11:59608648-59608648
GRCh38: 11:59841175-59841175
7 CBLIF NM_005142.3(CBLIF):c.137C>T (p.Ser46Leu) SNV Conflicting interpretations of pathogenicity 1746 rs121434322 GRCh37: 11:59611471-59611471
GRCh38: 11:59843998-59843998
8 CBLIF NM_005142.3(CBLIF):c.455C>T (p.Pro152Leu) SNV Conflicting interpretations of pathogenicity 305037 rs148081315 GRCh37: 11:59609972-59609972
GRCh38: 11:59842499-59842499
9 CBLIF NM_005142.3(CBLIF):c.910C>T (p.Pro304Ser) SNV Conflicting interpretations of pathogenicity 305032 rs150926439 GRCh37: 11:59603444-59603444
GRCh38: 11:59835971-59835971
10 CBLIF NM_005142.3(CBLIF):c.154T>A (p.Tyr52Asn) SNV Conflicting interpretations of pathogenicity 305044 rs144916324 GRCh37: 11:59611454-59611454
GRCh38: 11:59843981-59843981
11 CBLIF NM_005142.3(CBLIF):c.829G>C (p.Gly277Arg) SNV Uncertain significance 660115 rs138504371 GRCh37: 11:59604689-59604689
GRCh38: 11:59837216-59837216
12 CBLIF NM_005142.3(CBLIF):c.1064C>G (p.Pro355Arg) SNV Uncertain significance 1005545 GRCh37: 11:59603290-59603290
GRCh38: 11:59835817-59835817
13 CBLIF NM_005142.3(CBLIF):c.1190A>T (p.Glu397Val) SNV Uncertain significance 1008760 GRCh37: 11:59599153-59599153
GRCh38: 11:59831680-59831680
14 CBLIF NM_005142.3(CBLIF):c.1130C>T (p.Ala377Val) SNV Uncertain significance 971205 GRCh37: 11:59599213-59599213
GRCh38: 11:59831740-59831740
15 CBLIF NM_005142.3(CBLIF):c.446C>A (p.Ala149Glu) SNV Uncertain significance 1038547 GRCh37: 11:59609981-59609981
GRCh38: 11:59842508-59842508
16 CBLIF NM_005142.3(CBLIF):c.754A>T (p.Met252Leu) SNV Uncertain significance 1040504 GRCh37: 11:59604764-59604764
GRCh38: 11:59837291-59837291
17 CBLIF NM_005142.3(CBLIF):c.138G>A (p.Ser46=) SNV Uncertain significance 761936 rs200472519 GRCh37: 11:59611470-59611470
GRCh38: 11:59843997-59843997
18 CBLIF NM_005142.3(CBLIF):c.26T>C (p.Leu9Pro) SNV Uncertain significance 877195 GRCh37: 11:59612901-59612901
GRCh38: 11:59845428-59845428
19 CBLIF NM_005142.3(CBLIF):c.*87G>A SNV Uncertain significance 878166 GRCh37: 11:59596870-59596870
GRCh38: 11:59829397-59829397
20 CBLIF NM_005142.3(CBLIF):c.1180C>T (p.Pro394Ser) SNV Uncertain significance 878167 GRCh37: 11:59599163-59599163
GRCh38: 11:59831690-59831690
21 CBLIF NM_005142.3(CBLIF):c.1074-3T>C SNV Uncertain significance 800190 rs370833765 GRCh37: 11:59599272-59599272
GRCh38: 11:59831799-59831799
22 CBLIF NM_005142.3(CBLIF):c.1074-14A>G SNV Uncertain significance 879624 GRCh37: 11:59599283-59599283
GRCh38: 11:59831810-59831810
23 CBLIF NM_005142.3(CBLIF):c.574G>A (p.Glu192Lys) SNV Uncertain significance 879625 GRCh37: 11:59608735-59608735
GRCh38: 11:59841262-59841262
24 CBLIF NM_005142.3(CBLIF):c.256+10C>T SNV Uncertain significance 719724 rs369960390 GRCh37: 11:59611342-59611342
GRCh38: 11:59843869-59843869
25 CBLIF NM_005142.3(CBLIF):c.239T>C (p.Met80Thr) SNV Uncertain significance 879991 GRCh37: 11:59611369-59611369
GRCh38: 11:59843896-59843896
26 CBLIF NM_005142.3(CBLIF):c.778G>C (p.Gly260Arg) SNV Uncertain significance 948439 GRCh37: 11:59604740-59604740
GRCh38: 11:59837267-59837267
27 CBLIF NM_005142.3(CBLIF):c.82G>A (p.Val28Ile) SNV Uncertain significance 945698 GRCh37: 11:59611526-59611526
GRCh38: 11:59844053-59844053
28 CBLIF NM_005142.3(CBLIF):c.1055G>A (p.Arg352His) SNV Uncertain significance 955587 GRCh37: 11:59603299-59603299
GRCh38: 11:59835826-59835826
29 CBLIF NM_005142.3(CBLIF):c.834G>C (p.Lys278Asn) SNV Uncertain significance 305034 rs886048403 GRCh37: 11:59604684-59604684
GRCh38: 11:59837211-59837211
30 CBLIF NM_005142.3(CBLIF):c.218A>G (p.Lys73Arg) SNV Uncertain significance 305043 rs139444835 GRCh37: 11:59611390-59611390
GRCh38: 11:59843917-59843917
31 CBLIF NM_005142.3(CBLIF):c.79+3G>A SNV Uncertain significance 305045 rs146396839 GRCh37: 11:59612845-59612845
GRCh38: 11:59845372-59845372
32 CBLIF NM_005142.3(CBLIF):c.524T>C (p.Met175Thr) SNV Uncertain significance 305036 rs886048404 GRCh37: 11:59608785-59608785
GRCh38: 11:59841312-59841312
33 CBLIF NM_005142.3(CBLIF):c.371-15C>T SNV Uncertain significance 305039 rs759810252 GRCh37: 11:59610071-59610071
GRCh38: 11:59842598-59842598
34 CBLIF NM_005142.3(CBLIF):c.1107C>T (p.Val369=) SNV Uncertain significance 305030 rs537424617 GRCh37: 11:59599236-59599236
GRCh38: 11:59831763-59831763
35 CBLIF NM_005142.3(CBLIF):c.854A>G (p.Gln285Arg) SNV Uncertain significance 305033 rs886048402 GRCh37: 11:59604664-59604664
GRCh38: 11:59837191-59837191
36 CBLIF NM_005142.3(CBLIF):c.*56T>G SNV Uncertain significance 305029 rs886048401 GRCh37: 11:59596901-59596901
GRCh38: 11:59829428-59829428
37 CBLIF NM_005142.3(CBLIF):c.379G>A (p.Ala127Thr) SNV Uncertain significance 305038 rs760404861 GRCh37: 11:59610048-59610048
GRCh38: 11:59842575-59842575
38 CBLIF NM_005142.3(CBLIF):c.1221C>G (p.His407Gln) SNV Uncertain significance 573386 rs148989677 GRCh37: 11:59596990-59596990
GRCh38: 11:59829517-59829517
39 CBLIF NM_005142.3(CBLIF):c.1163T>C (p.Phe388Ser) SNV Uncertain significance 574163 rs767310648 GRCh37: 11:59599180-59599180
GRCh38: 11:59831707-59831707
40 CBLIF NM_005142.3(CBLIF):c.1181del (p.Pro394fs) Deletion Uncertain significance 581451 rs1565206584 GRCh37: 11:59599162-59599162
GRCh38: 11:59831689-59831689
41 CBLIF NM_005142.3(CBLIF):c.232C>T (p.Gln78Ter) SNV Uncertain significance 632162 rs1565210437 GRCh37: 11:59611376-59611376
GRCh38: 11:59843903-59843903
42 CBLIF NM_005142.3(CBLIF):c.482T>G (p.Leu161Arg) SNV Uncertain significance 660502 rs200856492 GRCh37: 11:59609945-59609945
GRCh38: 11:59842472-59842472
43 CBLIF NM_005142.3(CBLIF):c.1221C>T (p.His407=) SNV Likely benign 750113 rs148989677 GRCh37: 11:59596990-59596990
GRCh38: 11:59829517-59829517
44 CBLIF NM_005142.3(CBLIF):c.381T>G (p.Ala127=) SNV Likely benign 762559 rs1590860111 GRCh37: 11:59610046-59610046
GRCh38: 11:59842573-59842573
45 CBLIF NM_005142.3(CBLIF):c.432_434GAA[1] (p.Lys145del) Microsatellite Likely benign 208192 rs770530971 GRCh37: 11:59609990-59609992
GRCh38: 11:59842517-59842519
46 CBLIF NM_005142.3(CBLIF):c.1138G>A (p.Val380Ile) SNV Benign/Likely benign 788331 rs144070828 GRCh37: 11:59599205-59599205
GRCh38: 11:59831732-59831732
47 CBLIF NM_005142.3(CBLIF):c.990C>T (p.Asn330=) SNV Benign 305031 rs2867802 GRCh37: 11:59603364-59603364
GRCh38: 11:59835891-59835891
48 CBLIF NM_005142.3(CBLIF):c.290T>C (p.Met97Thr) SNV Benign 305040 rs150884181 GRCh37: 11:59610581-59610581
GRCh38: 11:59843108-59843108
49 CBLIF NM_005142.3(CBLIF):c.68A>G (p.Gln23Arg) SNV Benign 1742 rs35211634 GRCh37: 11:59612859-59612859
GRCh38: 11:59845386-59845386
50 CBLIF NM_005142.3(CBLIF):c.246C>T (p.Ser82=) SNV Benign 305042 rs35792306 GRCh37: 11:59611362-59611362
GRCh38: 11:59843889-59843889

UniProtKB/Swiss-Prot genetic disease variations for Intrinsic Factor Deficiency:

72
# Symbol AA change Variation ID SNP ID
1 CBLIF p.Ser46Leu VAR_022743 rs121434322

Expression for Intrinsic Factor Deficiency

Search GEO for disease gene expression data for Intrinsic Factor Deficiency.

Pathways for Intrinsic Factor Deficiency

GO Terms for Intrinsic Factor Deficiency

Sources for Intrinsic Factor Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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