MCID: HMC042
MIFTS: 22

Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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

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

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

Name: Homocystinuria-Megaloblastic Anemia, Cble Complementation Type 57 75
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism, Cble Complementation Type 57 41 29 6 73
Homocystinuria-Megaloblastic Anemia, Cbl E Type 57 13
Hmae 57 75
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism Cble Complementation Type 75
Anemia, Homocystinuria-Megaloblastic, Cble Complementation Type 40
Functional Methionine Synthase Deficiency Type Cble 59
Vitamin B12-Responsive Homocystinuria, Cble Type 57
Vitamin B12-Responsive Homocystinuria Cble Type 75
Methylcobalamin Deficiency, Cble Type 57
Methylcobalamin Deficiency Type Cble 59
Methylcobalamin Deficiency Cble Type 75

Characteristics:

Orphanet epidemiological data:

59
methylcobalamin deficiency type cble
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
symptoms are responsive to cobalamin treatment


HPO:

32
homocystinuria-megaloblastic anemia, cble complementation type:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Homocystinuria-Megaloblastic Anemia, Cble 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 (MTR; 156570). Clinical features are somewhat variable, but include delayed psychomotor development, hypotonia, 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 and CblG (250940) (Watkins and Rosenblatt, 1988). 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). CblG is caused by mutation in the MTR gene. (236270)

MalaCards based summary : Homocystinuria-Megaloblastic Anemia, Cble Complementation Type, is also known as homocystinuria-megaloblastic anemia due to defect in cobalamin metabolism, cble complementation type, and has symptoms including seizures An important gene associated with Homocystinuria-Megaloblastic Anemia, Cble Complementation Type is MTRR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase Reductase). Related phenotypes are nystagmus and muscular hypotonia

UniProtKB/Swiss-Prot : 75 Homocystinuria-megaloblastic anemia, cblE 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. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.

Related Diseases for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
cerebral atrophy
hypotonia
delayed psychomotor development
abnormal gait

Hematology:
megaloblastic anemia

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

Growth Other:
failure to thrive

Muscle Soft Tissue:
hypotonia

Laboratory Abnormalities:
homocystinuria
hyperhomocystinemia
hypomethioninemia


Clinical features from OMIM:

236270

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

59 32 (show all 21)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 nystagmus 59 32 occasional (7.5%) Frequent (79-30%) HP:0000639
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 respiratory insufficiency 59 32 frequent (33%) Frequent (79-30%) HP:0002093
4 anemia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001903
5 decreased nerve conduction velocity 59 32 hallmark (90%) Very frequent (99-80%) HP:0000762
6 cerebral cortical atrophy 59 32 frequent (33%) Frequent (79-30%) HP:0002120
7 intellectual disability, progressive 59 32 hallmark (90%) Very frequent (99-80%) HP:0006887
8 decreased methylcobalamin 59 32 hallmark (90%) Very frequent (99-80%) HP:0003223
9 seizures 32 HP:0001250
10 gait disturbance 32 HP:0001288
11 failure to thrive 32 HP:0001508
12 global developmental delay 32 HP:0001263
13 blindness 32 occasional (7.5%) HP:0000618
14 lethargy 32 HP:0001254
15 cerebral atrophy 32 HP:0002059
16 generalized hypotonia 32 HP:0001290
17 megaloblastic anemia 32 HP:0001889
18 homocystinuria 32 HP:0002156
19 hyperhomocystinemia 32 HP:0002160
20 hypomethioninemia 32 HP:0003658
21 decreased methionine synthase activity 32 HP:0003524

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


seizures

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

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

Genetic Tests for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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

# Genetic test Affiliating Genes
1 Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism, Cble Complementation Type 29 MTRR

Anatomical Context for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

Publications for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

Variations for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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

75
# Symbol AA change Variation ID SNP ID
1 MTRR p.Val83Met VAR_012838 rs761061866
2 MTRR p.Ala156Thr VAR_012839
3 MTRR p.Cys432Arg VAR_012841
4 MTRR p.Gly514Arg VAR_012842 rs137853061
5 MTRR p.Gly581Arg VAR_015731

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

6
(show all 24)
# Gene Variation Type Significance SNP ID Assembly Location
1 MTRR MTRR, 4-BP DEL, NT1675 deletion Pathogenic
2 MTRR MTRR, 3-BP DEL, 1726TTG deletion Pathogenic
3 MTRR NM_002454.2(MTRR): c.1459G> A (p.Gly487Arg) single nucleotide variant Pathogenic rs137853061 GRCh37 Chromosome 5, 7892928: 7892928
4 MTRR NM_002454.2(MTRR): c.1459G> A (p.Gly487Arg) single nucleotide variant Pathogenic rs137853061 GRCh38 Chromosome 5, 7892815: 7892815
5 MTRR MTRR, 2-BP INS, 1623TA insertion Pathogenic
6 MTRR MTRR, 140-BP INS, NT903 insertion Pathogenic
7 MTRR NM_002454.2(MTRR): c.1361C> T (p.Ser454Leu) single nucleotide variant Pathogenic rs137853062 GRCh37 Chromosome 5, 7891518: 7891518
8 MTRR NM_002454.2(MTRR): c.1361C> T (p.Ser454Leu) single nucleotide variant Pathogenic rs137853062 GRCh38 Chromosome 5, 7891405: 7891405
9 MTRR NM_002454.2(MTRR): c.1653G> A (p.Pro551=) single nucleotide variant Conflicting interpretations of pathogenicity rs139206262 GRCh38 Chromosome 5, 7895829: 7895829
10 MTRR NM_002454.2(MTRR): c.1653G> A (p.Pro551=) single nucleotide variant Conflicting interpretations of pathogenicity rs139206262 GRCh37 Chromosome 5, 7895942: 7895942
11 MTRR NM_002454.2(MTRR): c.210C> G (p.Arg70=) single nucleotide variant Conflicting interpretations of pathogenicity rs41282641 GRCh37 Chromosome 5, 7873566: 7873566
12 MTRR NM_002454.2(MTRR): c.210C> G (p.Arg70=) single nucleotide variant Conflicting interpretations of pathogenicity rs41282641 GRCh38 Chromosome 5, 7873453: 7873453
13 MTRR NM_002454.2(MTRR): c.869T> C (p.Ile290Thr) single nucleotide variant Uncertain significance rs144899305 GRCh38 Chromosome 5, 7883243: 7883243
14 MTRR NM_002454.2(MTRR): c.869T> C (p.Ile290Thr) single nucleotide variant Uncertain significance rs144899305 GRCh37 Chromosome 5, 7883356: 7883356
15 MTRR NM_002454.2(MTRR): c.828G> A (p.Val276=) single nucleotide variant Benign/Likely benign rs115289458 GRCh37 Chromosome 5, 7883315: 7883315
16 MTRR NM_002454.2(MTRR): c.828G> A (p.Val276=) single nucleotide variant Benign/Likely benign rs115289458 GRCh38 Chromosome 5, 7883202: 7883202
17 MTRR NM_002454.2(MTRR): c.1468A> G (p.Thr490Ala) single nucleotide variant Benign rs41283145 GRCh37 Chromosome 5, 7892937: 7892937
18 MTRR NM_002454.2(MTRR): c.1468A> G (p.Thr490Ala) single nucleotide variant Benign rs41283145 GRCh38 Chromosome 5, 7892824: 7892824
19 MTRR NM_002454.2(MTRR): c.209G> A (p.Arg70His) single nucleotide variant Uncertain significance rs777202031 GRCh37 Chromosome 5, 7873565: 7873565
20 MTRR NM_002454.2(MTRR): c.209G> A (p.Arg70His) single nucleotide variant Uncertain significance rs777202031 GRCh38 Chromosome 5, 7873452: 7873452
21 MTRR NM_002454.2(MTRR): c.1379T> G (p.Leu460Ter) single nucleotide variant Pathogenic GRCh38 Chromosome 5, 7892735: 7892735
22 MTRR NM_002454.2(MTRR): c.1379T> G (p.Leu460Ter) single nucleotide variant Pathogenic GRCh37 Chromosome 5, 7892848: 7892848
23 MTRR NM_002454.2(MTRR): c.1246T> C (p.Phe416Leu) single nucleotide variant Uncertain significance rs769915505 GRCh38 Chromosome 5, 7889194: 7889194
24 MTRR NM_002454.2(MTRR): c.1246T> C (p.Phe416Leu) single nucleotide variant Uncertain significance rs769915505 GRCh37 Chromosome 5, 7889307: 7889307

Expression for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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

Pathways for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

GO Terms for Homocystinuria-Megaloblastic Anemia, Cble Complementation Type

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