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 54 12 24 56 71 29 13 52 14 69
Tcn2 Deficiency 12 71
Inherited Deficiency of Transcobalamin 56
Transcobalamin Deficiency 56
Transcobalamin Ii 13

Characteristics:

Orphanet epidemiological data:

56
transcobalamin deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

54
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:

32
transcobalamin ii deficiency:
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Transcobalamin Ii Deficiency

OMIM : 54
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 transcobalamin deficiency, and has symptoms including neutropenia, methylmalonic aciduria and pancytopenia. An important gene associated with Transcobalamin Ii Deficiency is TCN2 (Transcobalamin 2), and among its related pathways/superpathways are Metabolism and HIV Life Cycle. Affiliated tissues include testes, bone and kidney, and related phenotype is Increased shRNA abundance (Z-score > 2).

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

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.

Related Diseases for Transcobalamin Ii Deficiency

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

(show all 38)
id Related Disease Score Top Affiliating Genes
1 homocystinuria 28.0 MMAA MMD MTHFR MTR MUT
2 transcobalamin deficiency 11.0
3 vulvar vestibulitis syndrome 10.5 MMAA MTR
4 color blindness 10.5 GIF TCN1 TCN2
5 congenital intrinsic factor deficiency 10.4 MTR MTRR
6 x-linked disease 10.4 MTR MTRR
7 factor v leiden thrombophilia 10.3 MTR MTRR
8 body dysmorphic disorder 10.3 MMAA MMADHC MUT
9 embryonal rhabdomyosarcoma 10.3 MTR TCN2
10 methylmalonic aciduria and homocystinuria, cblc type 10.1 MMD MTR
11 cd19-related common variable immune deficiency 10.0 LMBRD1 MTR MUT TCN2
12 corneal dystrophy, avellino type 10.0 KCNJ11 SLC35G5
13 hailey-hailey disease 10.0 MMAA MUT
14 parasitic protozoa infectious disease 9.9 KCNJ11 PMS2
15 homocystinuria due to mthfr deficiency 9.9 MTHFR MTR
16 prostatic cyst 9.9 KCNJ11 SLC35G5
17 colorectal cancer 9.7
18 megaloblastic anemia 9.7
19 astrocytoma 9.7
20 retinitis 9.7
21 retinal degeneration 9.7
22 hereditary colorectal cancer 9.7
23 bone ewing's sarcoma 9.7 DHFR MTHFR
24 hereditary nephrotic syndromes, autosomal dominant 9.6 MTHFR PMS2 TCN2
25 neural tube defects, folate-sensitive 9.6 MTHFR MTR MTRR
26 homologous wasting disease 9.6 MTHFR MTR MTRR
27 ectopic pregnancy 9.6 MTHFR MTR MTRR
28 ehlers-danlos syndrome, type viic 9.5 MTHFR MTR MTRR
29 priapism 9.5 MTHFR MTR MTRR
30 orbital disease 9.4 MTHFR MTR MTRR
31 methylmalonic aciduria and homocystinuria type cblg 9.3 GIF MTHFR MTR TCN1 TCN2
32 pericarditis 9.1 MTHFR MTR MTRR
33 neural tube defects 8.9 DHFR MTHFR MTR MTRR TCN2
34 primary cerebellar degeneration 8.8 LMBRD1 MMADHC MTHFR MTR MTRR TCN2
35 serine deficiency 8.7 GIF MMADHC MTHFR MTR MUT TCN1
36 calcaneonavicular coalition 8.6 LMBRD1 MMAA MMADHC MTHFR MTR MUT
37 vaginal glandular tumor 7.9 DHFR GIF LMBRD1 MMADHC MTHFR MTR
38 agammaglobulinemia 2 5.2 DHFR GIF KCNJ11 LMBRD1 MMAA MMADHC

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:

54

Growth- Other:
failure to thrive

Abdomen- Gastroin testinal:
diarrhea
vomiting

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
Immunology:
decreased iga
decreased igg
decreased igm

Hematology:
neutropenia
pancytopenia
reticulocytopenia
macrocytic anemia
megaloblastic bone marrow

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

Muscle Soft Tissue:
weakness

Head And Neck- Mouth:
mucosal ulceration


Clinical features from OMIM:

275350

Human phenotypes related to Transcobalamin Ii Deficiency:

56 32 (show all 23)
id Description HPO Frequency Orphanet Frequency HPO Source Accession
1 neutropenia 56 32 Frequent (79-30%) HP:0001875
2 methylmalonic aciduria 56 32 Very frequent (99-80%) HP:0012120
3 pancytopenia 56 32 Frequent (79-30%) HP:0001876
4 iga deficiency 56 32 Frequent (79-30%) HP:0002720
5 igg deficiency 56 32 Frequent (79-30%) HP:0004315
6 megaloblastic bone marrow 56 32 Very frequent (99-80%) HP:0001980
7 igm deficiency 56 32 Frequent (79-30%) HP:0002850
8 failure to thrive 32 HP:0001508
9 ataxia 32 HP:0001251
10 diarrhea 32 HP:0002014
11 lethargy 32 HP:0001254
12 thrombocytopenia 56 Frequent (79-30%)
13 irritability 32 HP:0000737
14 lymphopenia 56 Frequent (79-30%)
15 muscle weakness 32 HP:0001324
16 vomiting 32 HP:0002013
17 intellectual disability 32 HP:0001249
18 reticulocytopenia 32 HP:0001896
19 macrocytic anemia 32 HP:0001972
20 decreased antibody level in blood 56 Frequent (79-30%)
21 abnormality of the mouth 32 HP:0000153
22 abnormality of chromosome stability 56 Very frequent (99-80%)
23 acute kidney injury 56 Very frequent (99-80%)

UMLS symptoms related to Transcobalamin Ii Deficiency:


diarrhea, lethargy, vomiting, weakness

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

26
id Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-105 9.62 PMS2 MTRR
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 MTRR PMS2 TCN2
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:

id Genetic test Affiliating Genes
1 Transcobalamin Ii Deficiency 29 24 TCN2

Anatomical Context for Transcobalamin Ii Deficiency

MalaCards organs/tissues related to Transcobalamin Ii Deficiency:

39
Testes, Bone, Kidney, Bone Marrow, Globus Pallidus

Publications for Transcobalamin Ii Deficiency

Articles related to Transcobalamin Ii Deficiency:

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

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 GeneCards Suite gene sharing:

id Super pathways Score Top Affiliating Genes
1
Show member pathways
13.73 DHFR GIF KCNJ11 LMBRD1 MMAA MMADHC
2
Show member pathways
13.41 GIF KCNJ11 MMAA MMADHC MTR MTRR
3
Show member pathways
12.3 DHFR GIF LMBRD1 MMAA MMADHC MTHFR
4
Show member pathways
11.97 MTHFR MTR MUT
5
Show member pathways
11.8 DHFR MTHFR MTR MTRR TCN2
6
Show member pathways
11.68 GIF MMAA MMADHC MTR MTRR MUT
7 10.95 DHFR MTHFR
8 10.92 GIF LMBRD1 TCN2
9 10.62 GIF LMBRD1 MMAA MMADHC MTR MTRR
10
Show member pathways
10.18 MTR MTRR

GO Terms for Transcobalamin Ii Deficiency

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

(show all 11)
id 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 cobalt ion transport GO:0006824 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 cobalamin transport GO:0015889 9.26 GIF LMBRD1 TCN1 TCN2

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

id 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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 MedGen
42 MeSH
43 MESH via Orphanet
44 MGI
46 NCI
47 NCIt
48 NDF-RT
51 NINDS
52 Novoseek
54 OMIM
55 OMIM via Orphanet
59 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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