MCID: ADN090
MIFTS: 32

Adenosylcobalamin Deficiency

Categories: Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Adenosylcobalamin Deficiency

MalaCards integrated aliases for Adenosylcobalamin Deficiency:

Name: Adenosylcobalamin Deficiency 20 58
Vitamin B12-Responsive Methylmalonic Acidemia 20 58
Vitamin B12-Responsive Methylmalonic Aciduria 20 58
Defect in the Transport or Synthesis of Adenosyl-Cobalamin 20

Characteristics:

Orphanet epidemiological data:

58
vitamin b12-responsive methylmalonic acidemia
Inheritance: Autosomal recessive; Age of onset: Childhood;

Classifications:

Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism


Summaries for Adenosylcobalamin Deficiency

GARD : 20 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 28DefinitionAn inborn error of vitamin B12 (cobalamin) metabolism characterized by recurrent ketoacidotic comas or transient vomiting, dehydration, hypotonia and intellectual deficit, which responds to vitamin B12. There are three types: cblA, cblB and cblD-variant 2 (cblDv2).EpidemiologyTo date, over 120 patients with cblA, 66 patients with cblB and 6 patients with cblDv2 have been reported. Prevalence of 1/48,000-1/61,000 have been reported for methylmalonic acidemia (MA) of all causes in North America, and 1/26,000 in China, but only a subset of this is vitamin B12-responsive MA.Clinical descriptionPatients usually present in infancy or early childhood with features including lethargy, failure to thrive, recurrent vomiting, dehydration, respiratory distress, muscle hypotonia, hepatomegaly and coma. They may also show signs of anemia (not megaloblastic), have potentially life-threatening ketoacidosis and/or hyperammonemia, and developmental delay and intellectual deficit, with metabolic stroke affecting the brain stem. MA frequently leads to end-stage renal failure by adolescence or adulthood. Patients with cblB are usually more severely affected than patients with cblA.EtiologyVitamin B12-responsive MA is caused by defects in the synthesis of adenosylcobalamin (AdoCbl). There are three distinct complementation classes, cblA, B and Dv2. cblA is caused by mutations in the MMAA gene (4q31.1-2); cblB by the MMAB gene (12q24.1); and cblDv2 by the MMADHC gene (2q23.2). The previously reported cblH disorder has been shown to be cblDv2.Diagnostic methodsDiagnosis is based on increased methylmalonic acid in blood and urine. Neonatal screening for propionylcarnitine and/or increased propionylcarnitine-to-acetylcarnitine ratio in dried blood spots by tandem mass spectrometry (MS/MS) has become common, but specific identification of methylmalonic acid remains crucial.Differential diagnosisDifferential diagnoses include MA with homocystinuria (see this term), caused by defects in cblC, D and F, which can be differentiated by the presence of megaloblastic anemia, or vitamin B12-unresponsive MA without homocystinuria (see this term), which also can present early in life (<1 to 4 weeks) with similar symptoms. Complementation analysis can be used to identify the group involved, or sequencing of the causative genes to identify the affected gene.Antenatal diagnosisAntenatal diagnosis is possible by measurement of methylmalonate in amniotic fluid and maternal urine at mid-trimester and by studies of functional mutase activity and cobalamin metabolism in cultured amniotic fluid cells. Molecular diagnosis is possible if the gene affected and the mutation(s) in the family are known.Genetic counselingTransmission is autosomal recessive (1 in 4 recurrence risk/pregnancy).Management and treatmentTreatment involves a protein-restricted diet, which should be instituted as soon as life-threatening manifestations such as ketoacidosis or hyperammonemia have been resolved, and intramuscular injections of vitamin B12, with or without carnitine (mainly effective in cblA). A good response to cobalamin supplementation has been reported in most cblA patients and in nearly half cblB patients. Oral antibiotics may also be useful to reduce propionic acid from gut flora.PrognosisThe prognosis varies with the complement involved, with cblA patients having the most favorable prognosis (most patients well at ages up to 30 years) and cblB patients less favorable. cblDv2 appears similar to cblA, although the number of patients is small. One complication in long-term surviving patients is chronic renal failure.Visit the Orphanet disease page for more resources.

MalaCards based summary : Adenosylcobalamin Deficiency, also known as vitamin b12-responsive methylmalonic acidemia, is related to methylmalonic aciduria, cbla type and isolated methylmalonic acidemia. An important gene associated with Adenosylcobalamin Deficiency is MMAA (Metabolism Of Cobalamin Associated A), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Cobalamin (Cbl, vitamin B12) transport and metabolism. Related phenotypes are failure to thrive and nausea and vomiting

Related Diseases for Adenosylcobalamin Deficiency

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

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria, cbla type 32.4 MMAB MMAA
2 isolated methylmalonic acidemia 30.5 MMAB MMAA
3 methylmalonic acidemia 30.5 MMAB MMAA
4 methylmalonic aciduria, cblb type 11.9
5 methylmalonic aciduria and homocystinuria, cbld type 11.5
6 vitamin metabolic disorder 9.7 MMAB MMAA
7 methylmalonic aciduria and homocystinuria, cblc type 9.7 MMAB MMAA
8 organic acidemia 9.6 MMAB MMAA
9 amino acid metabolic disorder 9.6 MMAB MMAA
10 propionic acidemia 9.5 MMAB MMAA

Graphical network of the top 20 diseases related to Adenosylcobalamin Deficiency:



Diseases related to Adenosylcobalamin Deficiency

Symptoms & Phenotypes for Adenosylcobalamin Deficiency

Human phenotypes related to Adenosylcobalamin Deficiency:

58 31 (show all 14)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 failure to thrive 58 31 hallmark (90%) Very frequent (99-80%) HP:0001508
2 nausea and vomiting 58 31 hallmark (90%) Very frequent (99-80%) HP:0002017
3 respiratory insufficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0002093
4 hepatomegaly 58 31 hallmark (90%) Very frequent (99-80%) HP:0002240
5 dehydration 58 31 hallmark (90%) Very frequent (99-80%) HP:0001944
6 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
7 coma 58 31 hallmark (90%) Very frequent (99-80%) HP:0001259
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
10 hyperammonemia 58 31 frequent (33%) Frequent (79-30%) HP:0001987
11 hypotonia 31 frequent (33%) HP:0001252
12 renal insufficiency 58 31 occasional (7.5%) Occasional (29-5%) HP:0000083
13 anemia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001903
14 muscular hypotonia 58 Frequent (79-30%)

Drugs & Therapeutics for Adenosylcobalamin Deficiency

Search Clinical Trials , NIH Clinical Center for Adenosylcobalamin Deficiency

Genetic Tests for Adenosylcobalamin Deficiency

Anatomical Context for Adenosylcobalamin Deficiency

Publications for Adenosylcobalamin Deficiency

Articles related to Adenosylcobalamin Deficiency:

# Title Authors PMID Year
1
Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. 6 61
15523652 2004
2
Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies. 6
24813872 2015
3
Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type. 6
20556797 2010
4
Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. 6
12471062 2002
5
Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. 6
12438653 2002
6
The cause of multiple sclerosis is autoimmune attack of adenosyltransferase thereby limiting adenosylcobalamin production. 61
29150289 2017
7
Assay for methylmalonyl coenzyme A mutase activity based on determination of succinyl coenzyme A by ultrahigh-performance liquid chromatography tandem mass spectrometry. 61
26018627 2015
8
Accumulation of odd-numbered long-chain fatty acids in fetuses and neonates with inherited disorders of propionate metabolism. 61
1852536 1991
9
New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria. 61
3725502 1986

Variations for Adenosylcobalamin Deficiency

ClinVar genetic disease variations for Adenosylcobalamin Deficiency:

6 (show top 50) (show all 429)
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 MMAB NM_052845.4(MMAB):c.290G>A (p.Gly97Glu) SNV Pathogenic 218326 rs864309511 12:110006575-110006575 12:109568770-109568770
2 MMAB NM_052845.4(MMAB):c.567_569CCG[3] (p.Arg191dup) Microsatellite Pathogenic 218327 rs864309512 12:109998856-109998857 12:109561051-109561052
3 MMAA NM_172250.3(MMAA):c.562+1G>A SNV Pathogenic 225188 rs869320656 4:146563638-146563638 4:145642486-145642486
4 MMAB NM_052845.4(MMAB):c.563T>G (p.Val188Gly) SNV Pathogenic 225186 rs869320654 12:109998866-109998866 12:109561061-109561061
5 MMAA NM_172250.3(MMAA):c.1025T>G (p.Met342Arg) SNV Pathogenic 225189 rs869320657 4:146576354-146576354 4:145655202-145655202
6 MMAB NM_052845.4(MMAB):c.2T>C (p.Met1Thr) SNV Pathogenic 225187 rs869320655 12:110011284-110011284 12:109573479-109573479
7 MMAA NM_172250.3(MMAA):c.503del (p.Thr168fs) Deletion Pathogenic 218974 rs864309728 4:146563578-146563578 4:145642426-145642426
8 MMAA NM_172250.3(MMAA):c.620A>G (p.Tyr207Cys) SNV Pathogenic 3159 rs104893849 4:146567195-146567195 4:145646043-145646043
9 MMAA MMAA, 8-BP INS, NT260 Insertion Pathogenic 3157
10 MMAB NM_052845.4(MMAB):c.573_577del (p.Ala192fs) Deletion Pathogenic 3097 rs1555274497 12:109998852-109998856 12:109561047-109561051
11 MMAA NM_172250.3(MMAA):c.441dup (p.Leu148fs) Duplication Pathogenic 440800 rs1553958126 4:146563515-146563516 4:145642363-145642364
12 MMAA NM_172250.3(MMAA):c.575G>A (p.Gly192Asp) SNV Pathogenic 440803 rs1553958392 4:146567150-146567150 4:145645998-145645998
13 MMAA NM_172250.3(MMAA):c.658G>A (p.Val220Met) SNV Pathogenic 440805 rs150376474 4:146567233-146567233 4:145646081-145646081
14 MMAA NM_172250.3(MMAA):c.820-1G>A SNV Pathogenic 440808 rs1553959017 4:146575145-146575145 4:145653993-145653993
15 MMAA NM_172250.3(MMAA):c.1034del (p.Phe345fs) Deletion Pathogenic 96532 rs398124552 4:146576361-146576361 4:145655209-145655209
16 MMAA NM_172250.3(MMAA):c.72C>A (p.Tyr24Ter) SNV Pathogenic 440795 rs1553957883 4:146560363-146560363 4:145639211-145639211
17 MMAA NM_172250.3(MMAA):c.290_296del (p.Gln97fs) Deletion Pathogenic 440798 rs1553957907 4:146560575-146560581 4:145639423-145639429
18 MMAA NM_172250.3(MMAA):c.721A>T (p.Ile241Phe) SNV Pathogenic 440806 rs756221585 4:146567296-146567296 4:145646144-145646144
19 MMAA NM_172250.3(MMAA):c.455del (p.Pro152fs) Deletion Pathogenic 440801 rs1553958127 4:146563526-146563526 4:145642374-145642374
20 MMAA NM_172250.3(MMAA):c.860C>A (p.Ala287Asp) SNV Pathogenic 440809 rs1553959024 4:146575186-146575186 4:145654034-145654034
21 MMAA NM_172250.3(MMAA):c.1196_1197delinsTT (p.Gly399Val) Indel Pathogenic 440811 rs1553959152 4:146576525-146576526 4:145655373-145655374
22 MMAA NM_172250.3(MMAA):c.202C>T (p.Gln68Ter) SNV Pathogenic 440796 rs754894257 4:146560493-146560493 4:145639341-145639341
23 MMAA NM_172250.3(MMAA):c.298_312del (p.Cys100_Ala104del) Deletion Pathogenic 440799 rs780082584 4:146560585-146560599 4:145639433-145639447
24 MMAA NM_172250.3(MMAA):c.525_526TG[1] (p.Val176fs) Microsatellite Pathogenic 440802 rs1553958158 4:146563600-146563601 4:145642448-145642449
25 MMAA NM_172250.3(MMAA):c.651dup (p.Gly218fs) Duplication Pathogenic 440804 rs1314623572 4:146567225-146567226 4:145646073-145646074
26 MMAA NM_172250.3(MMAA):c.728C>A (p.Thr243Asn) SNV Pathogenic 440807 rs1553958417 4:146567303-146567303 4:145646151-145646151
27 MMAA NM_172250.3(MMAA):c.875A>T (p.Asp292Val) SNV Pathogenic 440810 rs1553959025 4:146575201-146575201 4:145654049-145654049
28 MMAA NM_172250.3(MMAA):c.267_268del (p.Thr91fs) Deletion Pathogenic 440797 rs1553957906 4:146560557-146560558 4:145639405-145639406
29 MMAB NM_052845.4(MMAB):c.585-2A>C SNV Pathogenic 550985 rs1555274254 12:109996962-109996962 12:109559157-109559157
30 MMAA NM_172250.3(MMAA):c.450dup (p.Pro151fs) Duplication Pathogenic 551182 rs754973022 4:146563522-146563523 4:145642370-145642371
31 MMAA NM_172250.3(MMAA):c.551dup (p.Cys184fs) Duplication Pathogenic 554640 rs1553958159 4:146563625-146563626 4:145642473-145642474
32 MMAA NM_172250.3(MMAA):c.970-2A>T SNV Pathogenic 555331 rs1553959113 4:146576297-146576297 4:145655145-145655145
33 MMAA NM_172250.3(MMAA):c.137_138CT[1] (p.Leu47fs) Microsatellite Pathogenic 570176 rs1560795828 4:146560427-146560428 4:145639275-145639276
34 MMAA NC_000004.12:g.(?_145639120)_(145642505_?)del Deletion Pathogenic 830599 4:146560272-146563657
35 MMAB NM_052845.4(MMAB):c.468G>A (p.Trp156Ter) SNV Pathogenic 834947 12:109999276-109999276 12:109561471-109561471
36 MMAA NM_172250.3(MMAA):c.762dup (p.Asp255Ter) Duplication Pathogenic 849500 4:146572241-146572242 4:145651089-145651090
37 MMAA NM_172250.3(MMAA):c.1229T>A (p.Leu410Ter) SNV Pathogenic 915363 4:146576558-146576558 4:145655406-145655406
38 MMAA NM_172250.3(MMAA):c.742C>T (p.Gln248Ter) SNV Pathogenic 496554 rs757548934 4:146572222-146572222 4:145651070-145651070
39 MMAB NM_052845.4(MMAB):c.700C>T (p.Gln234Ter) SNV Pathogenic 203820 rs369296618 12:109994886-109994886 12:109557081-109557081
40 MMAB NM_052845.4(MMAB):c.287T>C (p.Ile96Thr) SNV Pathogenic 218323 rs864309509 12:110006578-110006578 12:109568773-109568773
41 MMAB NM_052845.4(MMAB):c.571C>T (p.Arg191Trp) SNV Pathogenic 218324 rs376128990 12:109998858-109998858 12:109561053-109561053
42 MMAA NM_172250.3(MMAA):c.593_596del (p.Thr198fs) Deletion Pathogenic 203815 rs796051993 4:146567165-146567168 4:145646013-145646016
43 MMAA NM_172250.3(MMAA):c.562G>C (p.Gly188Arg) SNV Pathogenic 218975 rs864309729 4:146563637-146563637 4:145642485-145642485
44 MMAB NM_052845.4(MMAB):c.197-1G>T SNV Pathogenic 219008 rs763935916 12:110006669-110006669 12:109568864-109568864
45 MMAA NM_172250.3(MMAA):c.64C>T (p.Arg22Ter) SNV Pathogenic 218969 rs765799472 4:146560355-146560355 4:145639203-145639203
46 MMAA NM_172250.3(MMAA):c.314dup (p.Thr106fs) Duplication Pathogenic 961272 4:146560604-146560605 4:145639452-145639453
47 MMAA NM_172250.3(MMAA):c.697G>T (p.Gly233Ter) SNV Pathogenic 962079 4:146567272-146567272 4:145646120-145646120
48 MMAB NM_052845.4(MMAB):c.556C>T (p.Arg186Trp) SNV Pathogenic 3095 rs28941784 12:109998873-109998873 12:109561068-109561068
49 MMAA NM_172250.3(MMAA):c.283C>T (p.Gln95Ter) SNV Pathogenic 3158 rs104893846 4:146560574-146560574 4:145639422-145639422
50 MMAA NM_172250.3(MMAA):c.988C>T (p.Arg330Ter) SNV Pathogenic 203816 rs571038432 4:146576317-146576317 4:145655165-145655165

Expression for Adenosylcobalamin Deficiency

Search GEO for disease gene expression data for Adenosylcobalamin Deficiency.

Pathways for Adenosylcobalamin Deficiency

GO Terms for Adenosylcobalamin Deficiency

Cellular components related to Adenosylcobalamin Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrial matrix GO:0005759 8.62 MMAB MMAA

Biological processes related to Adenosylcobalamin Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cobalamin metabolic process GO:0009235 8.96 MMAB MMAA
2 cobalamin biosynthetic process GO:0009236 8.62 MMAB MMAA

Sources for Adenosylcobalamin Deficiency

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-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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