MCID: HMC033
MIFTS: 29

Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Neuronal diseases, Nephrological 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 53 49 71
Methylcobalamin Deficiency, Cblg Type 53 28 13 69
Methionine Synthase Deficiency 53 49 71
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism, Cblg Complementation Type 53 38
Hmag 53 71
Homocystinuria-Megaloblastic Anemia Due to Defect in Cobalamin Metabolism Cblg Complementation Type 71
Functional Methionine Synthase Deficiency Type Cblg 55
Methylcobalamin Deficiency Cbl G Type 49
Methylcobalamin Deficiency Type Cblg 55
Methylcobalamin Deficiency Cblg Type 71
Arakawa Syndrome 2 69
Cblg 49

Characteristics:

Orphanet epidemiological data:

55
methylcobalamin deficiency type cblg
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: All ages;

OMIM:

53
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:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type

OMIM : 53 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, nystagmus and intellectual disability. An important gene associated with Homocystinuria-Megaloblastic Anemia, Cblg Complementation Type is MTR (5-Methyltetrahydrofolate-Homocysteine Methyltransferase).

NIH Rare Diseases : 49 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. Last updated: 12/3/2015

UniProtKB/Swiss-Prot : 71 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 folate malabsorption, hereditary 11.2
4 homocystinuria-megaloblastic anemia, cble complementation type 11.1
5 methylmalonic aciduria and homocystinuria, cbld type 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:

53
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:

31 (show all 17)
# Description HPO Frequency HPO Source Accession
1 seizures 31 HP:0001250
2 nystagmus 31 occasional (7.5%) HP:0000639
3 intellectual disability 31 HP:0001249
4 gait disturbance 31 HP:0001288
5 failure to thrive 31 HP:0001508
6 global developmental delay 31 HP:0001263
7 blindness 31 occasional (7.5%) HP:0000618
8 feeding difficulties in infancy 31 HP:0008872
9 poor coordination 31 HP:0002370
10 cerebral atrophy 31 HP:0002059
11 generalized hypotonia 31 HP:0001290
12 megaloblastic anemia 31 HP:0001889
13 decreased methylcobalamin 31 HP:0003223
14 homocystinuria 31 HP:0002156
15 hyperhomocystinemia 31 HP:0002160
16 hypomethioninemia 31 HP:0003658
17 decreased methionine synthase activity 31 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 28 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
Defects in auxiliary redox proteins lead to functional methionine synthase deficiency. ( 9235907 )
1997
6
Folate-responsive homocystinuria and megaloblastic anaemia in a female patient with functional methionine synthase deficiency (cblE disease). ( 9427140 )
1997
7
Functional methionine synthase deficiency due to cblG disorder: a report of two patients and a review. ( 9286442 )
1997
8
Methionine synthase deficiency without megaloblastic anaemia. ( 9453374 )
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:

71
# 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 all 11)
# 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.2640_2642delAAT (p.Ile881del) deletion Pathogenic rs797044443 GRCh37 Chromosome 1, 237044100: 237044102
3 MTR NM_000254.2(MTR): c.2758C> G (p.His920Asp) single nucleotide variant Pathogenic rs121913579 GRCh37 Chromosome 1, 237048502: 237048502
4 MTR MTR, IVS3AS, A-G, -166 single nucleotide variant Pathogenic
5 MTR NM_000254.2(MTR): c.2114_2115delTC (p.Leu705Glnfs) deletion Pathogenic rs797044444 GRCh37 Chromosome 1, 237024495: 237024496
6 MTR MTR, IVS6AS, G-A, LYS203 single nucleotide variant Pathogenic
7 MTR NM_000254.2(MTR): c.3380dupA (p.Ala1128Glyfs) duplication Pathogenic rs797044445 GRCh37 Chromosome 1, 237057832: 237057832
8 MTR NM_000254.2(MTR): c.1753C> T (p.Arg585Ter) single nucleotide variant Pathogenic rs121913580 GRCh37 Chromosome 1, 237015878: 237015878
9 MTR NM_000254.2(MTR): c.3613G> T (p.Glu1205Ter) single nucleotide variant Pathogenic rs121913581 GRCh37 Chromosome 1, 237060320: 237060320
10 MTR NM_000254.2(MTR): c.1228G> C (p.Ala410Pro) single nucleotide variant Pathogenic rs121913582 GRCh37 Chromosome 1, 236998886: 236998886
11 MTR NM_000254.2(MTR): c.2669_2670delTG (p.Val890Glyfs) deletion Pathogenic rs794727395 GRCh37 Chromosome 1, 237044129: 237044130

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

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