MCID: MGL018
MIFTS: 42

Megaloblastic Anemia 1

Categories: Genetic diseases, Rare diseases, Gastrointestinal diseases, Nephrological diseases, Metabolic diseases, Blood diseases

Aliases & Classifications for Megaloblastic Anemia 1

MalaCards integrated aliases for Megaloblastic Anemia 1:

Name: Megaloblastic Anemia 1 57 53 25
Imerslund-Grasbeck Syndrome 57 53 25 75 55
Enterocyte Cobalamin Malabsorption 57 53 25
Pernicious Anemia, Juvenile, Due to Selective Intestinal Malabsorption of Vitamin B12, with Proteinuria 57 53
Selective Cobalamin Malabsorption with Proteinuria 53 59
Defect of Enterocyte Intrinsic Factor Receptor 53 25
Megaloblastic Anemia-1, Finnish Type 57 13
Familial Megaloblastic Anemia 53 59
Gräsbeck-Imerslund Disease 53 59
Igs 57 53
Juvenile Pernicious Anemia with Proteinuria Due to Selective Intestinal Malabsorption of Vitamin B12 25
Megaloblastic Anemia Due to Inborn Errors of Metabolism 73
Enterocyte Intrinsic Factor Receptor, Defect of 57
Recessive Hereditary Megaloblastic Anemia 1 75
Megaloblastic Anemia-1, Norwegian Type 57
Megaloblastic Anemia 1, Norwegian Type 6
Megaloblastic Anemia 1, Finnish Type 6
3-@methylglutaconic Aciduria, Type I 73
Imerslund-Grasbeck Syndrome; Igs 57
Anemia, Megaloblastic, Type 1 40
Imerslund-Gräsbeck Syndrome 25
Mga1 Norwegian Type 75
Rh-Mga1 75
Mga1 57
I-Gs 75

Characteristics:

Orphanet epidemiological data:

59
gräsbeck-imerslund disease
Inheritance: Autosomal recessive; Prevalence: 1-9/1000000 (Finland),1-9/1000000 (Norway); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
early childhood onset (before age 5 years)


HPO:

32
megaloblastic anemia 1:
Onset and clinical course childhood onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 261100
Orphanet 59 ORPHA35858
UMLS via Orphanet 74 C1306856
ICD10 via Orphanet 34 D51.1
MedGen 42 C1306856

Summaries for Megaloblastic Anemia 1

Genetics Home Reference : 25 Imerslund-Gräsbeck syndrome is a condition caused by low levels of vitamin B12 (also known as cobalamin). The primary feature of this condition is a blood disorder called megaloblastic anemia. In this form of anemia, which is a disorder characterized by the shortage of red blood cells, the red cells that are present are abnormally large. About half of people with Imerslund-Gräsbeck syndrome also have high levels of protein in their urine (proteinuria). Although proteinuria can be an indication of kidney problems, people with Imerslund-Gräsbeck syndrome appear to have normal kidney function.

MalaCards based summary : Megaloblastic Anemia 1, also known as imerslund-grasbeck syndrome, is related to 3-methylglutaconic aciduria, type i and megaloblastic anemia, and has symptoms including athetosis and cerebellar ataxia. An important gene associated with Megaloblastic Anemia 1 is CUBN (Cubilin), and among its related pathways/superpathways are HIV Life Cycle and Metabolism of water-soluble vitamins and cofactors. Affiliated tissues include kidney, thyroid and skin, and related phenotypes are proteinuria and dementia

OMIM : 57 Imerslund-Grasbeck syndrome is a form of congenital megaloblastic anemia due to vitamin B12 deficiency caused by a defect in the vitamin B12/intrinsic factor receptor. See also congenital pernicious anemia due to a defect in intrinsic factor (261000). Adult pernicious anemia (170900) is a distinct autoimmune disorder associated with plasma autoantibodies to gastric parietal cells or gastric intrinsic factor. In these cases, there is gastric atrophy and a relatively high frequency of associated thyroiditis and myxedema. (261100)

UniProtKB/Swiss-Prot : 75 Recessive hereditary megaloblastic anemia 1: Due to selective malabsorption of vitamin B12. Defects in vitamin B12 absorption lead to impaired function of thymidine synthase. As a consequence DNA synthesis is interrupted. Rapidly dividing cells involved in erythropoiesis are particularly affected.

NIH Rare Diseases : 53 Imerslund-Grasbeck syndrome (IGS) is a rare condition characterized by vitamin B12 deficiency, often causing megaloblastic anemia. IGS usually appears in childhood. Other features may include failure to thrive, infections, and neurological damage. Mild proteinuria (with no signs of kidney disease) is present in about half of affected individuals. IGS is caused by mutations in either the CUBN or AMN gene and is inherited in an autosomal recessive manner. Treatment includes life-long vitamin B12 injections, with which affected individuals can stay healthy for decades.

Related Diseases for Megaloblastic Anemia 1

Diseases in the Megaloblastic Anemia family:

Megaloblastic Anemia 1

Diseases related to Megaloblastic Anemia 1 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 45)
# Related Disease Score Top Affiliating Genes
1 3-methylglutaconic aciduria, type i 31.3 AMN CUBN
2 megaloblastic anemia 30.0 AMN CUBN GIF
3 hyper-ige recurrent infection syndrome, autosomal dominant 12.5
4 hyper ige syndrome 12.3
5 hyper-ige recurrent infection syndrome, autosomal recessive 12.3
6 erythroderma, congenital, with palmoplantar keratoderma, hypotrichosis, and hyper-ige 12.2
7 congenital disorder of glycosylation, type ig 12.2
8 ige responsiveness, atopic 12.2
9 amelogenesis imperfecta, type ig 12.1
10 usher syndrome, type ig 11.9
11 selective ige deficiency disease 11.9
12 immunodeficiency 35 11.8
13 amelogenesis imperfecta hypoplastic type, ig 11.8
14 acquired monoclonal ig light chain-associated fanconi syndrome 11.8
15 epilepsy, idiopathic generalized 11.8
16 netherton syndrome 11.8
17 alg12-congenital disorder of glycosylation 11.6
18 immunodeficiency 23 11.5
19 immunodeficiency 11b with atopic dermatitis 11.5
20 iminoglycinuria 11.4
21 common variable immunodeficiency 11.4
22 immunodeficiency with hyper-igm, type 1 11.3
23 asthma 11.3
24 non-immunoglobulin-mediated membranoproliferative glomerulonephritis 11.3
25 agammaglobulinemia, x-linked 11.2
26 immunodeficiency with hyper-igm, type 4 11.2
27 allergic asthma 11.2
28 dermatitis, atopic, 2 11.1
29 asthma-related traits 4 11.1
30 epilepsy, idiopathic generalized 10 11.1
31 immunodeficiency with hyper-igm, type 2 11.0
32 immunodeficiency with hyper-igm, type 5 11.0
33 nephrotic syndrome, type 7 11.0
34 hyperglycinuria 10.9
35 peeling skin syndrome 1 10.9
36 omenn syndrome 10.9
37 asthma-related traits 1 10.9
38 asthma-related traits 2 10.9
39 asthma-related traits 5 10.9
40 asthma-related traits 7 10.9
41 cd40 ligand deficiency 10.9
42 thalassemia 10.0
43 vitamin b12 deficiency 9.0 AMN GIF
44 congenital intrinsic factor deficiency 8.7 AMN CUBN GIF
45 vitamin metabolic disorder 8.7 AMN CUBN GIF

Graphical network of the top 20 diseases related to Megaloblastic Anemia 1:



Diseases related to Megaloblastic Anemia 1

Symptoms & Phenotypes for Megaloblastic Anemia 1

Symptoms via clinical synopsis from OMIM:

57
Laboratory Abnormalities:
proteinuria
decreased levels of serum vitamin b12
normal serum folate levels

Neurologic Central Nervous System:
dementia
confusion

Hematology:
megaloblastic anemia, chronic, relapsing
pernicious anemia, not influenced by intrinsic factor

Neurologic Peripheral Nervous System:
peripheral neuropathy
sensory impairment
paresthesias

Abdomen Gastrointestinal:
malabsorption of vitamin b12 (cyanocobalamin)
normal intrinsic factor protein

Immunology:
no antibodies to intrinsic factor


Clinical features from OMIM:

261100

Human phenotypes related to Megaloblastic Anemia 1:

32 (show all 7)
# Description HPO Frequency HPO Source Accession
1 proteinuria 32 HP:0000093
2 dementia 32 HP:0000726
3 confusion 32 HP:0001289
4 megaloblastic anemia 32 HP:0001889
5 paresthesia 32 HP:0003401
6 sensory impairment 32 HP:0003474
7 malabsorption of vitamin b12 32 HP:0200118

UMLS symptoms related to Megaloblastic Anemia 1:


athetosis, cerebellar ataxia

Drugs & Therapeutics for Megaloblastic Anemia 1

Search Clinical Trials , NIH Clinical Center for Megaloblastic Anemia 1

Genetic Tests for Megaloblastic Anemia 1

Anatomical Context for Megaloblastic Anemia 1

MalaCards organs/tissues related to Megaloblastic Anemia 1:

41
Kidney, Thyroid, Skin, Neutrophil

Publications for Megaloblastic Anemia 1

Articles related to Megaloblastic Anemia 1:

(show all 16)
# Title Authors Year
1
A long-term follow-up of an Imerslund-Grasbeck syndrome patient with proteinuria. ( 23364648 )
2013
2
Reversible skin hyperpigmentation in Imerslund-Grasbeck syndrome. ( 24222293 )
2013
3
Imerslund-Grasbeck syndrome: new mutation in amnionless. ( 22631584 )
2012
4
Unusual cause of childhood anemia: Imerslund Grasbeck syndrome. ( 22219566 )
2011
5
Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. ( 21750092 )
2011
6
Marathon of eponyms: 9 Imerslund-Grasbeck syndrome (Juvenile pernicious anaemia). ( 20374509 )
2010
7
Imerslund-Grasbeck syndrome: association with diabetes mellitus. ( 19346573 )
2009
8
Imerslund-Grasbeck syndrome associated with recurrent aphthous stomatitis and defective neutrophil function. ( 17114957 )
2006
9
Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin. ( 10887099 )
2000
10
A case report of 46,XX,del(21)(q22) de novo deletion associated with Imerslund-Grasbeck syndrome. ( 9001810 )
1996
11
Imerslund-Grasbeck syndrome in a Chinese family with distinct skin lesions refractory to vitamin B12. ( 7962612 )
1994
12
Reversal of severe neurological abnormalities after vitamin B12 replacement in the Imerslund-Grasbeck syndrome. ( 1940989 )
1991
13
Imerslund-Grasbeck syndrome in a Libyan boy. ( 2475066 )
1989
14
Megaloblastic anemia characterized by microcytosis: Imerslund-Grasbeck syndrome with coexistent alpha-thalassemia. ( 3368285 )
1988
15
Absent ileal uptake of IF-bound vitamin B12 in vivo in the Imerslund-Grasbeck syndrome (familial vitamin B12 malabsorption with proteinuria). ( 3972280 )
1985
16
Failure to thrive associated with the Imerslund-Grasbeck syndrome. ( 7301700 )
1981

Variations for Megaloblastic Anemia 1

UniProtKB/Swiss-Prot genetic disease variations for Megaloblastic Anemia 1:

75
# Symbol AA change Variation ID SNP ID
1 AMN p.Thr41Ile VAR_015733 rs119478058
2 CUBN p.Pro1297Leu VAR_025288 rs121434430

ClinVar genetic disease variations for Megaloblastic Anemia 1:

6
(show top 50) (show all 206)
# Gene Variation Type Significance SNP ID Assembly Location
1 AMN AMN, 1-BP DEL, 14G deletion Pathogenic
2 AMN NM_030943.3(AMN): c.122C> T (p.Thr41Ile) single nucleotide variant Pathogenic rs119478058 GRCh37 Chromosome 14, 103390126: 103390126
3 AMN NM_030943.3(AMN): c.122C> T (p.Thr41Ile) single nucleotide variant Pathogenic rs119478058 GRCh38 Chromosome 14, 102923789: 102923789
4 AMN AMN, IVS3, A-G, -2 single nucleotide variant Pathogenic
5 CUBN NM_001081.3(CUBN): c.3890C> T (p.Pro1297Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121434430 GRCh37 Chromosome 10, 17083159: 17083159
6 CUBN NM_001081.3(CUBN): c.3890C> T (p.Pro1297Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121434430 GRCh38 Chromosome 10, 17041160: 17041160
7 CUBN CUBN, IVS6, C-G single nucleotide variant Pathogenic
8 CUBN CUBN, IVS23, G-T, +1 single nucleotide variant Pathogenic
9 CUBN NM_001081.3(CUBN): c.1230+1G> A single nucleotide variant Likely pathogenic rs386833766 GRCh37 Chromosome 10, 17147455: 17147455
10 CUBN NM_001081.3(CUBN): c.1230+1G> A single nucleotide variant Likely pathogenic rs386833766 GRCh38 Chromosome 10, 17105456: 17105456
11 CUBN NM_001081.3(CUBN): c.1436C> G (p.Ser479Ter) single nucleotide variant Likely pathogenic rs386833767 GRCh37 Chromosome 10, 17145218: 17145218
12 CUBN NM_001081.3(CUBN): c.1436C> G (p.Ser479Ter) single nucleotide variant Likely pathogenic rs386833767 GRCh38 Chromosome 10, 17103219: 17103219
13 CUBN NM_001081.3(CUBN): c.1526delG (p.Gly509Glufs) deletion Likely pathogenic rs386833768 GRCh37 Chromosome 10, 17145128: 17145128
14 CUBN NM_001081.3(CUBN): c.1526delG (p.Gly509Glufs) deletion Likely pathogenic rs386833768 GRCh38 Chromosome 10, 17103129: 17103129
15 CUBN NM_001081.3(CUBN): c.1530G> A (p.Lys510=) single nucleotide variant Likely pathogenic rs386833769 GRCh37 Chromosome 10, 17145124: 17145124
16 CUBN NM_001081.3(CUBN): c.1530G> A (p.Lys510=) single nucleotide variant Likely pathogenic rs386833769 GRCh38 Chromosome 10, 17103125: 17103125
17 CUBN NM_001081.3(CUBN): c.1838delG (p.Gly613Glufs) deletion Likely pathogenic rs386833770 GRCh37 Chromosome 10, 17130272: 17130272
18 CUBN NM_001081.3(CUBN): c.1838delG (p.Gly613Glufs) deletion Likely pathogenic rs386833770 GRCh38 Chromosome 10, 17088273: 17088273
19 CUBN NM_001081.3(CUBN): c.1865delC (p.Thr622Ilefs) deletion Pathogenic rs386833771 GRCh37 Chromosome 10, 17130245: 17130245
20 CUBN NM_001081.3(CUBN): c.1865delC (p.Thr622Ilefs) deletion Pathogenic rs386833771 GRCh38 Chromosome 10, 17088246: 17088246
21 CUBN NM_001081.3(CUBN): c.1951C> T (p.Arg651Ter) single nucleotide variant Likely pathogenic rs182512508 GRCh37 Chromosome 10, 17127755: 17127755
22 CUBN NM_001081.3(CUBN): c.1951C> T (p.Arg651Ter) single nucleotide variant Likely pathogenic rs182512508 GRCh38 Chromosome 10, 17085756: 17085756
23 CUBN NM_001081.3(CUBN): c.2068A> G (p.Ile690Val) single nucleotide variant Likely pathogenic rs386833772 GRCh37 Chromosome 10, 17127638: 17127638
24 CUBN NM_001081.3(CUBN): c.2068A> G (p.Ile690Val) single nucleotide variant Likely pathogenic rs386833772 GRCh38 Chromosome 10, 17085639: 17085639
25 CUBN NM_001081.3(CUBN): c.2486C> T (p.Ser829Leu) single nucleotide variant Likely pathogenic rs386833773 GRCh37 Chromosome 10, 17113564: 17113564
26 CUBN NM_001081.3(CUBN): c.2486C> T (p.Ser829Leu) single nucleotide variant Likely pathogenic rs386833773 GRCh38 Chromosome 10, 17071565: 17071565
27 CUBN NM_001081.3(CUBN): c.250C> T (p.Gln84Ter) single nucleotide variant Likely pathogenic rs386833774 GRCh37 Chromosome 10, 17171122: 17171122
28 CUBN NM_001081.3(CUBN): c.250C> T (p.Gln84Ter) single nucleotide variant Likely pathogenic rs386833774 GRCh38 Chromosome 10, 17129123: 17129123
29 CUBN NM_001081.3(CUBN): c.2515_2533del19 (p.Glu839Profs) deletion Likely pathogenic rs386833775 GRCh37 Chromosome 10, 17113517: 17113535
30 CUBN NM_001081.3(CUBN): c.2515_2533del19 (p.Glu839Profs) deletion Likely pathogenic rs386833775 GRCh38 Chromosome 10, 17071518: 17071536
31 CUBN NM_001081.3(CUBN): c.252+1G> A single nucleotide variant Likely pathogenic rs386833776 GRCh37 Chromosome 10, 17171119: 17171119
32 CUBN NM_001081.3(CUBN): c.252+1G> A single nucleotide variant Likely pathogenic rs386833776 GRCh38 Chromosome 10, 17129120: 17129120
33 CUBN NM_001081.3(CUBN): c.2614_2615delGA (p.Asp872Leufs) deletion Likely pathogenic rs386833777 GRCh37 Chromosome 10, 17113435: 17113436
34 CUBN NM_001081.3(CUBN): c.2614_2615delGA (p.Asp872Leufs) deletion Likely pathogenic rs386833777 GRCh38 Chromosome 10, 17071436: 17071437
35 CUBN NM_001081.3(CUBN): c.2673C> A (p.Cys891Ter) single nucleotide variant Likely pathogenic rs386833778 GRCh37 Chromosome 10, 17110722: 17110722
36 CUBN NM_001081.3(CUBN): c.2673C> A (p.Cys891Ter) single nucleotide variant Likely pathogenic rs386833778 GRCh38 Chromosome 10, 17068723: 17068723
37 CUBN NM_001081.3(CUBN): c.2949C> A (p.Tyr983Ter) single nucleotide variant Likely pathogenic rs386833779 GRCh37 Chromosome 10, 17110122: 17110122
38 CUBN NM_001081.3(CUBN): c.2949C> A (p.Tyr983Ter) single nucleotide variant Likely pathogenic rs386833779 GRCh38 Chromosome 10, 17068123: 17068123
39 CUBN NM_001081.3(CUBN): c.3056C> G (p.Ser1019Ter) single nucleotide variant Likely pathogenic rs386833780 GRCh37 Chromosome 10, 17107590: 17107590
40 CUBN NM_001081.3(CUBN): c.3056C> G (p.Ser1019Ter) single nucleotide variant Likely pathogenic rs386833780 GRCh38 Chromosome 10, 17065591: 17065591
41 CUBN NM_001081.3(CUBN): c.3096delT (p.Tyr1032Terfs) deletion Likely pathogenic rs386833781 GRCh37 Chromosome 10, 17107550: 17107550
42 CUBN NM_001081.3(CUBN): c.3096delT (p.Tyr1032Terfs) deletion Likely pathogenic rs386833781 GRCh38 Chromosome 10, 17065551: 17065551
43 CUBN NM_001081.3(CUBN): c.3577T> G (p.Trp1193Gly) single nucleotide variant Likely pathogenic rs386833783 GRCh37 Chromosome 10, 17087101: 17087101
44 CUBN NM_001081.3(CUBN): c.3577T> G (p.Trp1193Gly) single nucleotide variant Likely pathogenic rs386833783 GRCh38 Chromosome 10, 17045102: 17045102
45 CUBN NM_001081.3(CUBN): c.3749C> T (p.Ser1250Phe) single nucleotide variant Likely pathogenic rs386833784 GRCh37 Chromosome 10, 17085906: 17085906
46 CUBN NM_001081.3(CUBN): c.3749C> T (p.Ser1250Phe) single nucleotide variant Likely pathogenic rs386833784 GRCh38 Chromosome 10, 17043907: 17043907
47 CUBN NM_001081.3(CUBN): c.3999C> A (p.Cys1333Ter) single nucleotide variant Likely pathogenic rs386833785 GRCh37 Chromosome 10, 17083050: 17083050
48 CUBN NM_001081.3(CUBN): c.3999C> A (p.Cys1333Ter) single nucleotide variant Likely pathogenic rs386833785 GRCh38 Chromosome 10, 17041051: 17041051
49 CUBN NM_001081.3(CUBN): c.4115C> G (p.Thr1372Arg) single nucleotide variant Likely pathogenic rs386833786 GRCh37 Chromosome 10, 17061885: 17061885
50 CUBN NM_001081.3(CUBN): c.4115C> G (p.Thr1372Arg) single nucleotide variant Likely pathogenic rs386833786 GRCh38 Chromosome 10, 17019886: 17019886

Expression for Megaloblastic Anemia 1

Search GEO for disease gene expression data for Megaloblastic Anemia 1.

Pathways for Megaloblastic Anemia 1

Pathways related to Megaloblastic Anemia 1 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
12.98 AMN CUBN GIF
2
Show member pathways
12.1 AMN CUBN GIF
3
Show member pathways
11.94 AMN CUBN
4
Show member pathways
11.7 CUBN GIF
5
Show member pathways
11.3 AMN CUBN GIF
6 10.64 CUBN GIF
7 10.45 AMN CUBN GIF
8
Show member pathways
9.64 AMN CUBN GIF

GO Terms for Megaloblastic Anemia 1

Cellular components related to Megaloblastic Anemia 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 endosome membrane GO:0010008 9.43 AMN CUBN
2 lysosomal lumen GO:0043202 9.4 CUBN GIF
3 apical part of cell GO:0045177 9.37 AMN CUBN
4 endosome GO:0005768 9.33 AMN CUBN GIF
5 clathrin-coated pit GO:0005905 9.32 AMN CUBN
6 endocytic vesicle GO:0030139 9.26 AMN CUBN
7 brush border membrane GO:0031526 8.96 AMN CUBN
8 apical plasma membrane GO:0016324 8.8 AMN CUBN GIF

Biological processes related to Megaloblastic Anemia 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 receptor-mediated endocytosis GO:0006898 9.26 AMN CUBN
2 high-density lipoprotein particle clearance GO:0034384 9.16 AMN CUBN
3 cobalamin metabolic process GO:0009235 9.13 AMN CUBN GIF
4 cobalamin transport GO:0015889 8.8 AMN CUBN GIF

Molecular functions related to Megaloblastic Anemia 1 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cobalamin binding GO:0031419 8.62 CUBN GIF

Sources for Megaloblastic Anemia 1

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
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34 ICD10 via Orphanet
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37 KEGG
38 LifeMap
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42 MedGen
44 MeSH
45 MESH via Orphanet
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49 NCI
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
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74 UMLS via Orphanet
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