MCID: TRN022
MIFTS: 47

Transcobalamin Ii Deficiency

Categories: Genetic diseases, Immune diseases, Blood diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Transcobalamin Ii Deficiency

MalaCards integrated aliases for Transcobalamin Ii Deficiency:

Name: Transcobalamin Ii Deficiency 53 12 55 71 36 28 13 51 14 69
Tcn2 Deficiency 53 12 71
Inherited Deficiency of Transcobalamin 55
Transcobalamin Deficiency 55
Transcobalamin Ii 13
Tc Ii Deficiency 53

Characteristics:

Orphanet epidemiological data:

55
transcobalamin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

53
Inheritance:
autosomal recessive

Miscellaneous:
presentation at 3-6 weeks of age
severe infections in untreated patients with neutropenia
neurologic dysfunction is infrequent and associated with delayed diagnosis


HPO:

31
transcobalamin ii deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Transcobalamin Ii Deficiency

OMIM : 53 Transcobalamin II deficiency is an autosomal recessive disorder with onset in early infancy characterized by failure to thrive, megaloblastic anemia, and pancytopenia. Other features include methylmalonic aciduria, recurrent infections, and vomiting and diarrhea. Treatment with cobalamin results in clinical improvement, but the untreated disorder may result in mental retardation and neurologic abnormalities (summary by Haberle et al., 2009). Hall (1981) gave a clinically oriented review of congenital defects of vitamin B12 transport, and Frater-Schroder (1983) gave a genetically oriented review. (275350)

MalaCards based summary : Transcobalamin Ii Deficiency, also known as tcn2 deficiency, is related to homocystinuria and megaloblastic anemia, and has symptoms including pancytopenia, neutropenia and iga deficiency. An important gene associated with Transcobalamin Ii Deficiency is TCN2 (Transcobalamin 2), and among its related pathways/superpathways are Vitamin digestion and absorption and Metabolism. Affiliated tissues include kidney, bone and testes, and related phenotypes are Increased shRNA abundance (Z-score > 2) and Increased shRNA abundance (Z-score > 2)

Disease Ontology : 12 A vitamin B12 deficiency that is characterized by a lack of vitamin B12 intestinal absorption resulting from a deficiency in the B12 transport protein TCII.

UniProtKB/Swiss-Prot : 71 Transcobalamin II deficiency: Results in various forms of anemia.

Related Diseases for Transcobalamin Ii Deficiency

Diseases related to Transcobalamin Ii Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 29)
# Related Disease Score Top Affiliating Genes
1 homocystinuria 28.3 LMBRD1 MMADHC MTHFR MTR MTRR TCN2
2 megaloblastic anemia 27.3 DHFR GIF LMBRD1 MMADHC MTHFR MTR
3 transcobalamin deficiency 11.3
4 blood group, i system 10.3
5 vitamin b12-responsive methylmalonic acidemia 10.3 MMAA MTR
6 pernicious anemia 10.3 GIF TCN1 TCN2
7 methylmalonic aciduria and homocystinuria type cble 10.2 MTR MTRR
8 methylmalonic aciduria and homocystinuria type cblg 10.2 MTR MTRR
9 organic acidemia 10.1 MMAA MMADHC MUT
10 methylmalonic aciduria and homocystinuria, cblc type 9.8 MMD MTR
11 colorectal cancer 9.8
12 astrocytoma 9.8
13 retinitis 9.8
14 retinal degeneration 9.8
15 homocystinuria due to deficiency of n -methylenetetrahydrofolate reductase activity 9.8 MTHFR MTR
16 nondisjunction 9.8 MTHFR MTRR
17 corneal dystrophy, reis-bucklers type 9.6 KCNJ11 SLC35G5
18 pediatric osteosarcoma 9.6 DHFR MTHFR
19 neural tube defects, folate-sensitive 9.6 MTHFR MTR MTRR
20 myelomeningocele 9.6 MTHFR MTR MTRR
21 homocysteinemia 9.5 MTHFR MTR MTRR
22 anencephaly 9.5 MTHFR MTR MTRR
23 cleft lip 9.4 MTHFR MTR MTRR
24 vitamin b12 deficiency 9.4 GIF MTHFR MTR TCN1 TCN2
25 holocarboxylase synthetase deficiency 9.4 LMBRD1 MMD MTHFR MUT
26 neural tube defects 9.1 DHFR MTHFR MTR MTRR TCN2
27 vitamin metabolic disorder 9.0 GIF MMADHC MTHFR MTR MUT TCN1
28 amino acid metabolic disorder 8.8 MMAA MMD MTHFR MTR MTRR MUT
29 methylmalonic aciduria, cblb type 8.6 LMBRD1 MMAA MMADHC MTHFR MTR MTRR

Graphical network of the top 20 diseases related to Transcobalamin Ii Deficiency:



Diseases related to Transcobalamin Ii Deficiency

Symptoms & Phenotypes for Transcobalamin Ii Deficiency

Symptoms via clinical synopsis from OMIM:

53
Abdomen Gastroin testinal:
vomiting
diarrhea

Muscle Soft Tissue:
weakness

Hematology:
pancytopenia
neutropenia
macrocytic anemia
megaloblastic bone marrow
reticulocytopenia

Immunology:
decreased igg
decreased igm
decreased iga

Neurologic Central Nervous System:
lethargy
irritability
mental retardation (if untreated)
ataxia (if untreated)

Growth Other:
failure to thrive

Laboratory Abnormalities:
methylmalonic aciduria
normal serum cobalamin
normal serum folate
reduced unsaturated serum cobalamin binding capacity
abnormal schilling test (not normalized by addition of intrinsic factor)
more
Head And Neck Mouth:
mucosal ulceration


Clinical features from OMIM:

275350

Human phenotypes related to Transcobalamin Ii Deficiency:

55 31 (show all 23)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 pancytopenia 55 31 Frequent (79-30%) HP:0001876
2 neutropenia 55 31 Frequent (79-30%) HP:0001875
3 iga deficiency 55 31 Frequent (79-30%) HP:0002720
4 igm deficiency 55 31 Frequent (79-30%) HP:0002850
5 igg deficiency 55 31 Frequent (79-30%) HP:0004315
6 methylmalonic aciduria 55 31 Very frequent (99-80%) HP:0012120
7 megaloblastic bone marrow 55 31 Very frequent (99-80%) HP:0001980
8 ataxia 31 HP:0001251
9 vomiting 31 HP:0002013
10 diarrhea 31 HP:0002014
11 muscle weakness 31 HP:0001324
12 lethargy 31 HP:0001254
13 intellectual disability 31 HP:0001249
14 failure to thrive 31 HP:0001508
15 irritability 31 HP:0000737
16 thrombocytopenia 55 Frequent (79-30%)
17 decreased antibody level in blood 55 Frequent (79-30%)
18 abnormality of the mouth 31 HP:0000153
19 lymphopenia 55 Frequent (79-30%)
20 abnormality of chromosome stability 55 Very frequent (99-80%)
21 acute kidney injury 55 Very frequent (99-80%)
22 macrocytic anemia 31 HP:0001972
23 reticulocytopenia 31 HP:0001896

UMLS symptoms related to Transcobalamin Ii Deficiency:


weakness, vomiting, lethargy, diarrhea

GenomeRNAi Phenotypes related to Transcobalamin Ii Deficiency according to GeneCards Suite gene sharing:

25 (show all 17)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.62 MTRR PMS2
2 Increased shRNA abundance (Z-score > 2) GR00366-A-126 9.62 TCN2
3 Increased shRNA abundance (Z-score > 2) GR00366-A-147 9.62 MTRR
4 Increased shRNA abundance (Z-score > 2) GR00366-A-158 9.62 MTRR
5 Increased shRNA abundance (Z-score > 2) GR00366-A-161 9.62 PMS2
6 Increased shRNA abundance (Z-score > 2) GR00366-A-168 9.62 MTRR
7 Increased shRNA abundance (Z-score > 2) GR00366-A-19 9.62 PMS2
8 Increased shRNA abundance (Z-score > 2) GR00366-A-197 9.62 PMS2
9 Increased shRNA abundance (Z-score > 2) GR00366-A-207 9.62 PMS2
10 Increased shRNA abundance (Z-score > 2) GR00366-A-45 9.62 TCN2
11 Increased shRNA abundance (Z-score > 2) GR00366-A-47 9.62 MTRR
12 Increased shRNA abundance (Z-score > 2) GR00366-A-49 9.62 PMS2
13 Increased shRNA abundance (Z-score > 2) GR00366-A-56 9.62 TCN2 MTRR PMS2
14 Increased shRNA abundance (Z-score > 2) GR00366-A-63 9.62 PMS2
15 Increased shRNA abundance (Z-score > 2) GR00366-A-80 9.62 TCN2
16 Increased shRNA abundance (Z-score > 2) GR00366-A-92 9.62 MTRR
17 Increased shRNA abundance (Z-score > 2) GR00366-A-93 9.62 MTRR

Drugs & Therapeutics for Transcobalamin Ii Deficiency

Search Clinical Trials , NIH Clinical Center for Transcobalamin Ii Deficiency

Genetic Tests for Transcobalamin Ii Deficiency

Genetic tests related to Transcobalamin Ii Deficiency:

# Genetic test Affiliating Genes
1 Transcobalamin Ii Deficiency 28 TCN2

Anatomical Context for Transcobalamin Ii Deficiency

MalaCards organs/tissues related to Transcobalamin Ii Deficiency:

38
Kidney, Bone, Testes, Bone Marrow, Globus Pallidus

Publications for Transcobalamin Ii Deficiency

Articles related to Transcobalamin Ii Deficiency:

(show all 27)
# Title Authors Year
1
Trilineage dyspoiesis caused by transcobalamin II deficiency. ( 28522466 )
2017
2
Congenital Transcobalamin II Deficiency: A Rare Entity with a Broad Differential. ( 29132166 )
2017
3
Novel Mutation in an Indian Patient with Transcobalamin II Deficiency. ( 25947267 )
2015
4
Transcobalamin II Deficiency in Four Cases with Novel Mutations. ( 25914105 )
2015
5
Expanding the Spectrum of Methylmalonic Acid-Induced Pallidal Stroke: First Reported Case of Metabolic Globus Pallidus Stroke in Transcobalamin II Deficiency. ( 23430814 )
2013
6
Transcobalamin II deficiency at birth. ( 19581117 )
2009
7
Retinopathy in inherited Transcobalamin II deficiency. ( 18195238 )
2008
8
Multifocal anaplastic astrocytoma in a patient with hereditary colorectal cancer, transcobalamin II deficiency, agenesis of the corpus callosum, mental retardation, and inherited PMS2 mutation. ( 17993636 )
2008
9
Hereditary partial transcobalamin II deficiency with neurologic, mental and hematologic abnormalities in children and adults. ( 14689755 )
2003
10
Congenital transcobalamin II deficiency due to errors in RNA editing. ( 12064907 )
2002
11
Favorable long-term outcome of a patient with transcobalamin II deficiency. ( 12379088 )
2002
12
Retinal degeneration associated with congenital transcobalamin II deficiency. ( 11448334 )
2001
13
Transcobalamin II deficiency with methylmalonic aciduria in three sisters. ( 10518276 )
1999
14
[Transcobalamin II deficiency]. ( 9645045 )
1998
15
Hereditary transcobalamin II deficiency: a 22 year follow up. ( 9048724 )
1997
16
Long-term follow up of patients with transcobalamin II deficiency. ( 7741573 )
1995
17
Nonsense mutations in human transcobalamin II deficiency. ( 7980584 )
1994
18
Expression of transcobalamin II mRNA in human tissues and cultured fibroblasts from normal and transcobalamin II-deficient patients. ( 7913804 )
1994
19
Cytogenetic findings of a child with transcobalamin II deficiency. ( 8362900 )
1993
20
The neurologic aspects of transcobalamin II deficiency. ( 1536799 )
1992
21
Transcobalamin II deficiency: case report and review of the literature. ( 1743216 )
1991
22
Transcobalamin II deficiency presenting with methylmalonic aciduria and homocystinuria and abnormal absorption of cobalamin. ( 2309761 )
1990
23
Transcobalamin II deficiency: long-term follow-up of two cases. ( 3143215 )
1988
24
Prenatal studies in a family with transcobalamin II deficiency. ( 3661564 )
1987
25
Transcobalamin II deficiency and oral cobalamin therapy. ( 3697511 )
1986
26
Homozygous transcobalamin II deficiency maintained on oral hydroxocobalamin. ( 4052627 )
1985
27
Neonatal megaloblastic anemia due to inherited transcobalamin II deficiency in two siblings. ( 5096637 )
1971

Variations for Transcobalamin Ii Deficiency

ClinVar genetic disease variations for Transcobalamin Ii Deficiency:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 TCN2 NM_000355.3(TCN2): c.927_930delTCTG (p.Cys309Trpfs) deletion Pathogenic rs794728001 GRCh38 Chromosome 22, 30615774: 30615777
2 TCN2 NM_000355.3(TCN2): c.766dup (p.Ser256Phefs) duplication Pathogenic GRCh38 Chromosome 22, 30615613: 30615613

Expression for Transcobalamin Ii Deficiency

Search GEO for disease gene expression data for Transcobalamin Ii Deficiency.

Pathways for Transcobalamin Ii Deficiency

Pathways related to Transcobalamin Ii Deficiency according to KEGG:

36
# Name Kegg Source Accession
1 Vitamin digestion and absorption hsa04977

Pathways related to Transcobalamin Ii Deficiency according to GeneCards Suite gene sharing:

(show all 12)
# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.78 DHFR GIF KCNJ11 LMBRD1 MMAA MMADHC
2
Show member pathways
13.45 GIF KCNJ11 MMAA MMADHC MTR MTRR
3
Show member pathways
12.3 DHFR GIF LMBRD1 MMAA MMADHC MTHFR
4
Show member pathways
12.19 DHFR GIF MTHFR MTR MTRR MUT
5
Show member pathways
12.01 MTHFR MTR MUT
6
Show member pathways
11.87 DHFR MTHFR MTR MTRR TCN2
7
Show member pathways
11.68 GIF MMAA MMADHC MTR MTRR MUT
8 10.99 DHFR MTHFR
9 10.96 GIF LMBRD1 TCN2
10 10.62 GIF LMBRD1 MMAA MMADHC MTR MTRR
11
Show member pathways
10.23 MTR MTRR
12
Show member pathways
10.03 MMAA MUT

GO Terms for Transcobalamin Ii Deficiency

Biological processes related to Transcobalamin Ii Deficiency according to GeneCards Suite gene sharing:

(show all 11)
# Name GO ID Score Top Affiliating Genes
1 axon regeneration GO:0031103 9.49 DHFR MTR
2 tetrahydrofolate metabolic process GO:0046653 9.48 DHFR MTHFR
3 methionine biosynthetic process GO:0009086 9.46 MTR MTRR
4 sulfur amino acid metabolic process GO:0000096 9.43 MTR MTRR
5 folic acid metabolic process GO:0046655 9.43 DHFR MTHFR MTRR
6 methionine metabolic process GO:0006555 9.4 MTHFR MTRR
7 homocysteine metabolic process GO:0050667 9.37 MTHFR MUT
8 cobalamin transport GO:0015889 9.33 GIF TCN1 TCN2
9 short-chain fatty acid catabolic process GO:0019626 9.32 MMAA MUT
10 cobalamin metabolic process GO:0009235 9.28 GIF LMBRD1 MMAA MMADHC MTR MTRR
11 cobalt ion transport GO:0006824 9.13 GIF TCN1 TCN2

Molecular functions related to Transcobalamin Ii Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 NADPH binding GO:0070402 9.26 DHFR MTRR
2 modified amino acid binding GO:0072341 9.16 MTHFR MUT
3 NADP binding GO:0050661 9.13 DHFR MTHFR MTRR
4 cobalamin binding GO:0031419 9.1 GIF LMBRD1 MTR MUT TCN1 TCN2

Sources for Transcobalamin Ii Deficiency

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
16 ExPASy
18 FMA
27 GO
28 GTR
29 HGMD
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 MedGen
41 MeSH
42 MESH via Orphanet
43 MGI
45 NCI
46 NCIt
47 NDF-RT
50 NINDS
51 Novoseek
53 OMIM
54 OMIM via Orphanet
58 PubMed
60 QIAGEN
65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
69 UMLS
70 UMLS via Orphanet
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