MCID: HMC033
MIFTS: 29

Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Nephrological diseases, Metabolic diseases, Blood 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 53 75
Methylcobalamin Deficiency, Cblg Type 57 29 13 6 40 73
Methionine Synthase Deficiency 57 53 75
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism, Cblg Complementation Type 57 41
Hmag 57 75
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism Cblg Complementation Type 75
Functional Methionine Synthase Deficiency Type Cblg 59
Methylcobalamin Deficiency Cbl G Type 53
Methylcobalamin Deficiency Type Cblg 59
Methylcobalamin Deficiency Cblg Type 75
Arakawa Syndrome 2 73
Cblg 53

Characteristics:

Orphanet epidemiological data:

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

OMIM:

57
Inheritance:
autosomal recessive

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


HPO:

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


Classifications:



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)

MalaCards based summary : Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type, also known as methylcobalamin deficiency, cblg type, is related to methylmalonic aciduria and homocystinuria type cblg and homocystinuria without methylmalonic aciduria, and has symptoms including seizures An important gene associated with Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type is MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase). Related phenotypes are nystagmus and intellectual disability

NIH Rare Diseases : 53 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 : 75 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

Diseases related to Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria and homocystinuria type cblg 11.9
2 homocystinuria without methylmalonic aciduria 11.5
3 homocystinuria-megaloblastic anemia, cble complementation type 11.1
4 methylmalonic aciduria and homocystinuria, cbld type 11.1
5 folate malabsorption, hereditary 11.1
6 pulmonary hypertension 9.8
7 megaloblastic anemia 9.8
8 homocystinuria 9.8

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

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:

250940

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

32 (show all 17)
# Description HPO Frequency HPO Source Accession
1 nystagmus 32 occasional (7.5%) HP:0000639
2 intellectual disability 32 HP:0001249
3 seizures 32 HP:0001250
4 gait disturbance 32 HP:0001288
5 failure to thrive 32 HP:0001508
6 global developmental delay 32 HP:0001263
7 blindness 32 occasional (7.5%) HP:0000618
8 feeding difficulties in infancy 32 HP:0008872
9 poor coordination 32 HP:0002370
10 cerebral atrophy 32 HP:0002059
11 generalized hypotonia 32 HP:0001290
12 megaloblastic anemia 32 HP:0001889
13 decreased methylcobalamin 32 HP:0003223
14 homocystinuria 32 HP:0002156
15 hyperhomocystinemia 32 HP:0002160
16 hypomethioninemia 32 HP:0003658
17 decreased methionine synthase activity 32 HP:0003524

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, Cblg Type 29 MTR

Anatomical Context for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Publications for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

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

# Title Authors Year
1
Disturbed visual system function in methionine synthase deficiency. ( 15931548 )
2005
2
Hyperhomocysteinemia due to methionine synthase deficiency, cblG: structure of the MTR gene, genotype diversity, and recognition of a common mutation, P1173L. ( 12068375 )
2002
3
Haemolytic uraemic syndrome and pulmonary hypertension in a patient with methionine synthase deficiency. ( 10485306 )
1999
4
Functionally null mutations in patients with the cblG-variant form of methionine synthase deficiency. ( 9683607 )
1998
5
Methionine synthase deficiency without megaloblastic anaemia. ( 9453374 )
1997
6
Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease). ( 9427140 )
1997
7
Defects in auxiliary redox proteins lead to functional methionine synthase deficiency. ( 9235907 )
1997
8
Functional methionine synthase deficiency due to cblG disorder: a report of two patients and a review. ( 9286442 )
1997
9
Functional methionine synthase deficiency (cblE and cblG): clinical and biochemical heterogeneity. ( 2688421 )
1989
10
Megaloblastic anemia and immune abnormalities in a patient with methionine synthase deficiency. ( 3425320 )
1987

Variations for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

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

75
# Symbol AA change Variation ID SNP ID
1 MTR p.His920Asp VAR_004330 rs121913579
2 MTR p.Pro1173Leu VAR_004331 rs121913578

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

6
(show top 50) (show all 52)
# Gene Variation Type Significance SNP ID Assembly Location
1 MTR NM_000254.2(MTR): c.3518C> T (p.Pro1173Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121913578 GRCh37 Chromosome 1, 237058770: 237058770
2 MTR NM_000254.2(MTR): c.3518C> T (p.Pro1173Leu) single nucleotide variant Pathogenic/Likely pathogenic rs121913578 GRCh38 Chromosome 1, 236895470: 236895470
3 MTR NM_000254.2(MTR): c.2640_2642delAAT (p.Ile881del) deletion Pathogenic rs797044443 GRCh37 Chromosome 1, 237044100: 237044102
4 MTR NM_000254.2(MTR): c.2640_2642delAAT (p.Ile881del) deletion Pathogenic rs797044443 GRCh38 Chromosome 1, 236880800: 236880802
5 MTR NM_000254.2(MTR): c.2758C> G (p.His920Asp) single nucleotide variant Pathogenic rs121913579 GRCh37 Chromosome 1, 237048502: 237048502
6 MTR NM_000254.2(MTR): c.2758C> G (p.His920Asp) single nucleotide variant Pathogenic rs121913579 GRCh38 Chromosome 1, 236885202: 236885202
7 MTR MTR, IVS3AS, A-G, -166 single nucleotide variant Pathogenic
8 MTR NM_000254.2(MTR): c.2114_2115delTC (p.Leu705Glnfs) deletion Pathogenic rs797044444 GRCh37 Chromosome 1, 237024495: 237024496
9 MTR NM_000254.2(MTR): c.2114_2115delTC (p.Leu705Glnfs) deletion Pathogenic rs797044444 GRCh38 Chromosome 1, 236861195: 236861196
10 MTR MTR, IVS6AS, G-A, LYS203 single nucleotide variant Pathogenic
11 MTR NM_000254.2(MTR): c.3380dupA (p.Ala1128Glyfs) duplication Pathogenic rs797044445 GRCh37 Chromosome 1, 237057832: 237057832
12 MTR NM_000254.2(MTR): c.3380dupA (p.Ala1128Glyfs) duplication Pathogenic rs797044445 GRCh38 Chromosome 1, 236894532: 236894532
13 MTR NM_000254.2(MTR): c.1753C> T (p.Arg585Ter) single nucleotide variant Pathogenic rs121913580 GRCh37 Chromosome 1, 237015878: 237015878
14 MTR NM_000254.2(MTR): c.1753C> T (p.Arg585Ter) single nucleotide variant Pathogenic rs121913580 GRCh38 Chromosome 1, 236852578: 236852578
15 MTR NM_000254.2(MTR): c.3613G> T (p.Glu1205Ter) single nucleotide variant Pathogenic rs121913581 GRCh37 Chromosome 1, 237060320: 237060320
16 MTR NM_000254.2(MTR): c.3613G> T (p.Glu1205Ter) single nucleotide variant Pathogenic rs121913581 GRCh38 Chromosome 1, 236897020: 236897020
17 MTR NM_000254.2(MTR): c.1228G> C (p.Ala410Pro) single nucleotide variant Pathogenic rs121913582 GRCh37 Chromosome 1, 236998886: 236998886
18 MTR NM_000254.2(MTR): c.1228G> C (p.Ala410Pro) single nucleotide variant Pathogenic rs121913582 GRCh38 Chromosome 1, 236835586: 236835586
19 MTR NM_000254.2(MTR): c.2669_2670delTG (p.Val890Glyfs) deletion Pathogenic rs794727395 GRCh37 Chromosome 1, 237044129: 237044130
20 MTR NM_000254.2(MTR): c.2669_2670delTG (p.Val890Glyfs) deletion Pathogenic rs794727395 GRCh38 Chromosome 1, 236880829: 236880830
21 MTR NM_000254.2(MTR): c.858C> T (p.Pro286=) single nucleotide variant Benign/Likely benign rs146019467 GRCh37 Chromosome 1, 236987512: 236987512
22 MTR NM_000254.2(MTR): c.858C> T (p.Pro286=) single nucleotide variant Benign/Likely benign rs146019467 GRCh38 Chromosome 1, 236824212: 236824212
23 MTR NM_000254.2(MTR): c.1033G> A (p.Val345Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs145006491 GRCh38 Chromosome 1, 236829226: 236829226
24 MTR NM_000254.2(MTR): c.1033G> A (p.Val345Ile) single nucleotide variant Conflicting interpretations of pathogenicity rs145006491 GRCh37 Chromosome 1, 236992526: 236992526
25 MTR NM_000254.2(MTR): c.1437C> T (p.Asp479=) single nucleotide variant Conflicting interpretations of pathogenicity rs115424814 GRCh38 Chromosome 1, 236838521: 236838521
26 MTR NM_000254.2(MTR): c.1437C> T (p.Asp479=) single nucleotide variant Conflicting interpretations of pathogenicity rs115424814 GRCh37 Chromosome 1, 237001821: 237001821
27 MTR NM_000254.2(MTR): c.1076-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs115186224 GRCh38 Chromosome 1, 236831958: 236831958
28 MTR NM_000254.2(MTR): c.1076-8C> T single nucleotide variant Conflicting interpretations of pathogenicity rs115186224 GRCh37 Chromosome 1, 236995258: 236995258
29 MTR NM_000254.2(MTR): c.3496C> T (p.Leu1166=) single nucleotide variant Benign rs12030699 GRCh38 Chromosome 1, 236895448: 236895448
30 MTR NM_000254.2(MTR): c.3496C> T (p.Leu1166=) single nucleotide variant Benign rs12030699 GRCh37 Chromosome 1, 237058748: 237058748
31 MTR NM_000254.2(MTR): c.3599-10C> A single nucleotide variant Benign/Likely benign rs41530146 GRCh38 Chromosome 1, 236896996: 236896996
32 MTR NM_000254.2(MTR): c.3599-10C> A single nucleotide variant Benign/Likely benign rs41530146 GRCh37 Chromosome 1, 237060296: 237060296
33 MTR NM_000254.2(MTR): c.250-7G> A single nucleotide variant Benign/Likely benign rs184332230 GRCh38 Chromosome 1, 236806137: 236806137
34 MTR NM_000254.2(MTR): c.250-7G> A single nucleotide variant Benign/Likely benign rs184332230 GRCh37 Chromosome 1, 236969437: 236969437
35 MTR NM_000254.2(MTR): c.1080A> G (p.Leu360=) single nucleotide variant Conflicting interpretations of pathogenicity rs141861479 GRCh38 Chromosome 1, 236831970: 236831970
36 MTR NM_000254.2(MTR): c.1080A> G (p.Leu360=) single nucleotide variant Conflicting interpretations of pathogenicity rs141861479 GRCh37 Chromosome 1, 236995270: 236995270
37 MTR NM_000254.2(MTR): c.3665A> G (p.Asn1222Ser) single nucleotide variant Benign/Likely benign rs61739582 GRCh38 Chromosome 1, 236897072: 236897072
38 MTR NM_000254.2(MTR): c.3665A> G (p.Asn1222Ser) single nucleotide variant Benign/Likely benign rs61739582 GRCh37 Chromosome 1, 237060372: 237060372
39 MTR NM_000254.2(MTR): c.2622G> A (p.Pro874=) single nucleotide variant Likely benign rs141919148 GRCh37 Chromosome 1, 237044082: 237044082
40 MTR NM_000254.2(MTR): c.2622G> A (p.Pro874=) single nucleotide variant Likely benign rs141919148 GRCh38 Chromosome 1, 236880782: 236880782
41 MTR NC_000001.11: g.(?_236795684)_(236897664_?)del deletion Pathogenic GRCh38 Chromosome 1, 236795684: 236897664
42 MTR NC_000001.11: g.(?_236795684)_(236897664_?)del deletion Pathogenic GRCh37 Chromosome 1, 236958984: 237060964
43 MTR NM_000254.2(MTR): c.1067T> C (p.Leu356Ser) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 236829260: 236829260
44 MTR NM_000254.2(MTR): c.1067T> C (p.Leu356Ser) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 236992560: 236992560
45 MTR NM_000254.2(MTR): c.2165T> C (p.Leu722Pro) single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 237024546: 237024546
46 MTR NM_000254.2(MTR): c.2165T> C (p.Leu722Pro) single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 236861246: 236861246
47 MTR NM_000254.2(MTR): c.1575A> T (p.Lys525Asn) single nucleotide variant Uncertain significance rs199700767 GRCh37 Chromosome 1, 237013703: 237013703
48 MTR NM_000254.2(MTR): c.1575A> T (p.Lys525Asn) single nucleotide variant Uncertain significance rs199700767 GRCh38 Chromosome 1, 236850403: 236850403
49 MTR NM_000254.2(MTR): c.1954-6A> G single nucleotide variant Uncertain significance GRCh37 Chromosome 1, 237023127: 237023127
50 MTR NM_000254.2(MTR): c.1954-6A> G single nucleotide variant Uncertain significance GRCh38 Chromosome 1, 236859827: 236859827

Expression for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

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GO Terms for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

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