HMAG
MCID: HMC033
MIFTS: 35

Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type (HMAG)

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

Aliases & Classifications for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

MalaCards integrated aliases for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

Name: Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type 57 12 20 72
Methylcobalamin Deficiency, Cblg Type 57 12 13 39 70
Methylcobalamin Deficiency Type Cblg 58 29 6
Methionine Synthase Deficiency 57 20 72
Hmag 57 12 72
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism, Cblg Complementation Type 57 40
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism Cblg Complementation Type 12 72
Functional Methionine Synthase Deficiency Type Cblg 58
Homocystinuria-Megaloblastic Anemia Cblg Type 12
Methylcobalamin Deficiency Cbl G Type 20
Methylcobalamin Deficiency Cblg Type 72
Arakawa Syndrome 2 70
Cblg 20

Characteristics:

Orphanet epidemiological data:

58
methylcobalamin deficiency type cblg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM®:

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

Miscellaneous:
onset in infancy
later onset has been reported
symptoms are responsive to cobalamin treatment


HPO:

31
homocystinuria-megaloblastic anemia, cblg complementation type:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Inborn errors of metabolism
Rare haematological diseases


External Ids:

Disease Ontology 12 DOID:0112256
OMIM® 57 250940
MeSH 44 D008661
ICD10 via Orphanet 33 E72.1
UMLS via Orphanet 71 C1855128
Orphanet 58 ORPHA2170
MedGen 41 C1855128
UMLS 70 C0268611 C1855128

Summaries for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

OMIM® : 57 Homocystinuria and megaloblastic anemia is an autosomal recessive inborn error of metabolism resulting from defects in the cobalamin (vitamin B12)-dependent pathway that converts homocysteine to methionine, which is catalyzed by methionine synthase. Clinical features are somewhat variable, but include delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia, all of which respond to cobalamin supplementation. Methylmalonic aciduria is not present. Two complementation groups have been described based on fibroblast studies: CblE (236270) and CblG (Watkins and Rosenblatt, 1988). Most patients present in early infancy, but some patients with CblG have shown later onset (Outteryck et al., 2012). Cells from patients with CblE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent. Cells from patients with CblG have defects in the methionine synthase enzyme under both conditions (summary by Leclerc et al., 1996). CblE is caused by mutation in the MTRR gene (602568). Watkins and Rosenblatt (1989) commented on the clinical and biochemical heterogeneity in patients with cblE and cblG. (250940) (Updated 05-Apr-2021)

MalaCards based summary : Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type, also known as methylcobalamin deficiency, cblg type, is related to methylmalonic acidemia without homocystinuria and homocystinuria-megaloblastic anemia, cble complementation type, and has symptoms including seizures An important gene associated with Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type is MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase). Affiliated tissues include breast, and related phenotypes are nystagmus and blindness

Disease Ontology : 12 An amino acid metabolic disorder characterized by failure of cells to incorporate methyltetrahydrofolate into methionine, impaired methionine synthase activity in the presence of a reducing agent, and somewhat variable features that include delayed psychomotor development, hypotonia, megaloblastic anemia, homocystinuria, and hypomethioninemia that has material basis in homozygous or compound heterozygous mutation in MTR on chromosome 1q43.

GARD : 20 Methylcobalamin deficiency cbl G type is a rare condition that occurs when the body is unable to process certain amino acids (building blocks of protein ) properly. In most cases, signs and symptoms develop during the first year of life; however, the age of onset can range from infancy to adulthood. Common features of the condition include feeding difficulties, lethargy, seizures, poor muscle tone ( hypotonia ), developmental delay, microcephaly (unusually small head size), and megaloblastic anemia. Methylcobalamin deficiency cbl G type is caused by changes ( mutations ) in the MTR gene and is inherited in an autosomal recessive manner. Treatment generally includes regular doses of hydroxocobalamin (vitamin B12). Some affected people may also require supplementation with folates and betaine.

UniProtKB/Swiss-Prot : 72 Homocystinuria-megaloblastic anemia, cblG complementation type: An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia.

Related Diseases for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Graphical network of the top 20 diseases related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:



Diseases related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Symptoms & Phenotypes for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Human phenotypes related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 nystagmus 31 occasional (7.5%) HP:0000639
2 blindness 31 occasional (7.5%) HP:0000618
3 intellectual disability 31 HP:0001249
4 failure to thrive 31 HP:0001508
5 gait disturbance 31 HP:0001288
6 global developmental delay 31 HP:0001263
7 feeding difficulties in infancy 31 HP:0008872
8 cerebral atrophy 31 HP:0002059
9 generalized hypotonia 31 HP:0001290
10 megaloblastic anemia 31 HP:0001889
11 poor coordination 31 HP:0002370
12 hyperhomocystinemia 31 HP:0002160
13 hypomethioninemia 31 HP:0003658
14 homocystinuria 31 HP:0002156
15 decreased methylcobalamin 31 HP:0003223
16 seizure 31 HP:0001250
17 decreased methionine synthase activity 31 HP:0003524

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Neurologic Central Nervous System:
seizures
cerebral atrophy
hypotonia
abnormal gait
delayed psychomotor development

Hematology:
megaloblastic anemia

Muscle Soft Tissue:
hypotonia

Growth Other:
failure to thrive

Laboratory Abnormalities:
hyperhomocystinemia
hypomethioninemia
homocystinuria

Head And Neck Eyes:
nystagmus (in some patients)
blindness (in some patients)

Clinical features from OMIM®:

250940 (Updated 05-Apr-2021)

UMLS symptoms related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:


seizures

Drugs & Therapeutics for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Search Clinical Trials , NIH Clinical Center for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Genetic Tests for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Genetic tests related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

# Genetic test Affiliating Genes
1 Methylcobalamin Deficiency Type Cblg 29 MTR

Anatomical Context for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

MalaCards organs/tissues related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

40
Breast

Publications for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Articles related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

(show all 21)
# Title Authors PMID Year
1
Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L. 6 57
12068375 2002
2
Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency. 6 57
9683607 1998
3
Defects in human methionine synthase in cblG patients. 6 57
8968736 1996
4
Human methionine synthase: cDNA cloning and identification of mutations in patients of the cblG complementation group of folate/cobalamin disorders. 57 6
8968737 1996
5
Clinical onset and course, response to treatment and outcome in 24 patients with the cblE or cblG remethylation defect complemented by genetic and in vitro enzyme study data. 6
25526710 2015
6
Methionine synthase deficiency: a rare cause of adult-onset leukoencephalopathy. 57
22786600 2012
7
Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency. 57
10485306 1999
8
Methionine synthase deficiency without megaloblastic anaemia. 57
9453374 1997
9
Defects in auxiliary redox proteins lead to functional methionine synthase deficiency. 6
9235907 1997
10
Inherited disorders of vitamin B12 utilization. 57
2203337 1990
11
Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. 57
2688421 1989
12
The nature of the defect in cobalamin G mutation. 57
2535439 1989
13
Hereditary defect of cobalamin metabolism (cblG mutation) presenting as a neurologic disorder in adulthood. 57
2897628 1988
14
Genetic heterogeneity among patients with methylcobalamin deficiency. Definition of two complementation groups, cblE and cblG. 57
3384945 1988
15
Vitamin B12 responsive homocystinuria and megaloblastic anemia: heterogeneity in methylcobalamin deficiency. 57
3812589 1987
16
Megaloblastic anemia and mental retardation associated with hyperfolic-acidemia: probably due to N5 methyltetrahydrofolate transferase deficiency. 57
5300832 1967
17
A novel pharmacological approach of herbal mediated cerium oxide and silver nanoparticles with improved biomedical activity in comparison with Lawsonia inermis. 61
30465994 2019
18
Exploring the significance of sex hormone-binding globulin examination in the treament of women with polycystic ovarian syndrome (PCOS). 61
26152001 2015
19
Expression of human mammaglobin and clinicopathologic correlations in breast cancer: the findings in Malaysia. 61
21623075 2011
20
A recombinant replication-competent hepatitis C virus expressing Azami-Green, a bright green-emitting fluorescent protein, suitable for visualization of infected cells. 61
18786508 2008
21
Heterologous reactivity of in vitro cultured mouse cells with natural human serum antibodies. 61
327972 1977

Variations for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

ClinVar genetic disease variations for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

6 (show top 50) (show all 103)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 MTR MTR, IVS3AS, A-G, -166 SNV Pathogenic 14281 GRCh37:
GRCh38:
2 MTR NM_001291939.1(MTR):c.2044-1041_2044-1040del Microsatellite Pathogenic 14282 rs797044444 GRCh37: 1:237024492-237024493
GRCh38: 1:236861192-236861193
3 MTR MTR, IVS6AS, G-A, LYS203 SNV Pathogenic 14283 GRCh37:
GRCh38:
4 MTR NM_000254.2(MTR):c.3380dup (p.Ala1128fs) Duplication Pathogenic 14284 rs797044445 GRCh37: 1:237057830-237057831
GRCh38: 1:236894530-236894531
5 MTR NM_000254.2(MTR):c.1753C>T (p.Arg585Ter) SNV Pathogenic 14286 rs121913580 GRCh37: 1:237015878-237015878
GRCh38: 1:236852578-236852578
6 MTR NM_000254.2(MTR):c.3613G>T (p.Glu1205Ter) SNV Pathogenic 14287 rs121913581 GRCh37: 1:237060320-237060320
GRCh38: 1:236897020-236897020
7 MTR NM_000254.2(MTR):c.1228G>C (p.Ala410Pro) SNV Pathogenic 14288 rs121913582 GRCh37: 1:236998886-236998886
GRCh38: 1:236835586-236835586
8 MTR NM_000254.2(MTR):c.2640_2642del (p.Ile881del) Deletion Pathogenic 14279 rs797044443 GRCh37: 1:237044099-237044101
GRCh38: 1:236880799-236880801
9 MTR NC_000001.11:g.(?_236795684)_(236897664_?)del Deletion Pathogenic 534574 GRCh37: 1:236958984-237060964
GRCh38: 1:236795684-236897664
10 MTR NM_000254.2(MTR):c.3439C>T (p.Arg1147Ter) SNV Pathogenic 650018 rs201718371 GRCh37: 1:237058691-237058691
GRCh38: 1:236895391-236895391
11 MTR NM_000254.2(MTR):c.2476del (p.Asp825_Ile826insTer) Deletion Pathogenic 650287 rs1572309822 GRCh37: 1:237038028-237038028
GRCh38: 1:236874728-236874728
12 MTR NM_000254.2(MTR):c.1992_1993insATCA (p.Glu665fs) Insertion Pathogenic 648454 rs1572278166 GRCh37: 1:237023171-237023172
GRCh38: 1:236859871-236859872
13 MTR NM_000254.3(MTR):c.2474-1G>C SNV Pathogenic 930329 GRCh37: 1:237038025-237038025
GRCh38: 1:236874725-236874725
14 MTR NM_000254.3(MTR):c.610-1G>T SNV Pathogenic 931542 GRCh37: 1:236978903-236978903
GRCh38: 1:236815603-236815603
15 MTR NM_000254.3(MTR):c.2405+1G>A SNV Pathogenic 973489 GRCh37: 1:237026855-237026855
GRCh38: 1:236863555-236863555
16 MTR NM_000254.3(MTR):c.2473+3A>G SNV Pathogenic 973490 GRCh37: 1:237037143-237037143
GRCh38: 1:236873843-236873843
17 MTR NM_000254.3(MTR):c.2436T>A (p.Cys812Ter) SNV Pathogenic 998279 GRCh37: 1:237037103-237037103
GRCh38: 1:236873803-236873803
18 MTR NM_000254.3(MTR):c.3518C>T SNV Pathogenic 14278 rs121913578 GRCh37: 1:237058770-237058770
GRCh38: 1:236895470-236895470
19 MTR NM_000254.3(MTR):c.609+1088G>A SNV Pathogenic 1048517 GRCh37: 1:236977232-236977232
GRCh38: 1:236813932-236813932
20 MTR NM_000254.3(MTR):c.2788_2791del (p.Leu930fs) Deletion Pathogenic 1048518 GRCh37: 1:237049601-237049604
GRCh38: 1:236886301-236886304
21 MTR NM_000254.2(MTR):c.2305-1G>T SNV Likely pathogenic 854532 GRCh37: 1:237026753-237026753
GRCh38: 1:236863453-236863453
22 MTR NM_000254.2(MTR):c.2482G>A (p.Gly828Ser) SNV Likely pathogenic 801639 rs1413989228 GRCh37: 1:237038034-237038034
GRCh38: 1:236874734-236874734
23 MTR NM_000254.2(MTR):c.927+1G>C SNV Likely pathogenic 641704 rs1572218599 GRCh37: 1:236988700-236988700
GRCh38: 1:236825400-236825400
24 MTR NM_000254.2(MTR):c.1559A>G (p.Tyr520Cys) SNV Conflicting interpretations of pathogenicity 801638 rs1242741686 GRCh37: 1:237013687-237013687
GRCh38: 1:236850387-236850387
25 MTR NM_000254.3(MTR):c.2282T>A (p.Leu761His) SNV Uncertain significance 967416 GRCh37: 1:237025621-237025621
GRCh38: 1:236862321-236862321
26 MTR NM_000254.3(MTR):c.2966C>T (p.Pro989Leu) SNV Uncertain significance 1042051 GRCh37: 1:237052595-237052595
GRCh38: 1:236889295-236889295
27 MTR NM_000254.3(MTR):c.2326G>A (p.Val776Met) SNV Uncertain significance 1043299 GRCh37: 1:237026775-237026775
GRCh38: 1:236863475-236863475
28 MTR NM_000254.3(MTR):c.3032A>G (p.Asp1011Gly) SNV Uncertain significance 1044684 GRCh37: 1:237054457-237054457
GRCh38: 1:236891157-236891157
29 MTR NM_000254.3(MTR):c.2315A>G (p.Gln772Arg) SNV Uncertain significance 1047769 GRCh37: 1:237026764-237026764
GRCh38: 1:236863464-236863464
30 MTR NM_000254.3(MTR):c.68A>G (p.Asn23Ser) SNV Uncertain significance 1002650 GRCh37: 1:236966761-236966761
GRCh38: 1:236803461-236803461
31 MTR NM_000254.3(MTR):c.1953+3A>G SNV Uncertain significance 1003178 GRCh37: 1:237016391-237016391
GRCh38: 1:236853091-236853091
32 MTR NM_000254.3(MTR):c.1969G>C (p.Gly657Arg) SNV Uncertain significance 1006250 GRCh37: 1:237023148-237023148
GRCh38: 1:236859848-236859848
33 MTR NM_000254.3(MTR):c.755A>G (p.Glu252Gly) SNV Uncertain significance 1008682 GRCh37: 1:236979834-236979834
GRCh38: 1:236816534-236816534
34 MTR NM_000254.2(MTR):c.3035A>T (p.Asp1012Val) SNV Uncertain significance 296575 rs201901663 GRCh37: 1:237054460-237054460
GRCh38: 1:236891160-236891160
35 MTR NM_000254.2(MTR):c.2014G>A (p.Glu672Lys) SNV Uncertain significance 431870 rs142774813 GRCh37: 1:237023193-237023193
GRCh38: 1:236859893-236859893
36 MTR NM_000254.2(MTR):c.1074T>C (p.Ser358=) SNV Uncertain significance 642565 rs1430063160 GRCh37: 1:236992567-236992567
GRCh38: 1:236829267-236829267
37 MTR NM_000254.2(MTR):c.3490C>T (p.Arg1164Cys) SNV Uncertain significance 646496 rs761657622 GRCh37: 1:237058742-237058742
GRCh38: 1:236895442-236895442
38 MTR NM_000254.2(MTR):c.1522G>C (p.Glu508Gln) SNV Uncertain significance 646614 rs1572261571 GRCh37: 1:237013650-237013650
GRCh38: 1:236850350-236850350
39 MTR NM_000254.2(MTR):c.899C>T (p.Thr300Met) SNV Uncertain significance 572316 rs201871910 GRCh37: 1:236988671-236988671
GRCh38: 1:236825371-236825371
40 MTR NM_000254.2(MTR):c.2758C>G (p.His920Asp) SNV Uncertain significance 14280 rs121913579 GRCh37: 1:237048502-237048502
GRCh38: 1:236885202-236885202
41 MTR NM_000254.2(MTR):c.2165T>C (p.Leu722Pro) SNV Uncertain significance 534569 rs1553321807 GRCh37: 1:237024546-237024546
GRCh38: 1:236861246-236861246
42 MTR NM_000254.2(MTR):c.1575A>T (p.Lys525Asn) SNV Uncertain significance 534570 rs199700767 GRCh37: 1:237013703-237013703
GRCh38: 1:236850403-236850403
43 MTR NM_000254.2(MTR):c.1954-6A>G SNV Uncertain significance 534571 rs1553321372 GRCh37: 1:237023127-237023127
GRCh38: 1:236859827-236859827
44 MTR NM_000254.2(MTR):c.1067T>C (p.Leu356Ser) SNV Uncertain significance 534572 rs1286773616 GRCh37: 1:236992560-236992560
GRCh38: 1:236829260-236829260
45 MTR NM_000254.2(MTR):c.3140A>T (p.Tyr1047Phe) SNV Uncertain significance 649699 rs1572341910 GRCh37: 1:237054565-237054565
GRCh38: 1:236891265-236891265
46 MTR NM_000254.2(MTR):c.3514C>T (p.Arg1172Cys) SNV Uncertain significance 652449 rs756440911 GRCh37: 1:237058766-237058766
GRCh38: 1:236895466-236895466
47 MTR NM_000254.2(MTR):c.2684A>C (p.Gln895Pro) SNV Uncertain significance 660667 rs146569329 GRCh37: 1:237048428-237048428
GRCh38: 1:236885128-236885128
48 MTR NM_000254.2(MTR):c.2304+3A>C SNV Uncertain significance 663061 rs1572283994 GRCh37: 1:237025646-237025646
GRCh38: 1:236862346-236862346
49 MTR NM_000254.2(MTR):c.3227C>T (p.Thr1076Met) SNV Uncertain significance 664316 rs144991102 GRCh37: 1:237057679-237057679
GRCh38: 1:236894379-236894379
50 MTR NM_000254.2(MTR):c.866-10C>G SNV Uncertain significance 296554 rs368755647 GRCh37: 1:236988628-236988628
GRCh38: 1:236825328-236825328

UniProtKB/Swiss-Prot genetic disease variations for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type:

72
# Symbol AA change Variation ID SNP ID
1 MTR p.His920Asp VAR_004330 rs121913579
2 MTR p.Pro1173Leu VAR_004331 rs121913578

Expression for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Search GEO for disease gene expression data for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type.

Pathways for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

GO Terms for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Sources for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

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
Content
Loading form....