Adenosylcobalamin Deficiency

Categories: Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Adenosylcobalamin Deficiency

MalaCards integrated aliases for Adenosylcobalamin Deficiency:

Name: Adenosylcobalamin Deficiency 52 58
Vitamin B12-Responsive Methylmalonic Acidemia 52 58
Vitamin B12-Responsive Methylmalonic Aciduria 52 58
Defect in the Transport or Synthesis of Adenosyl-Cobalamin 52


Orphanet epidemiological data:

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


Orphanet: 58  
Rare renal diseases
Inborn errors of metabolism

Summaries for Adenosylcobalamin Deficiency

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 28 Definition An 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 (cblD v2). Epidemiology To date, over 120 patients with cblA , 66 patients with cblB and 6 patients with cblD v2 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 description Patients 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 . Etiology Vitamin B12-responsive MA is caused by defects in the synthesis of adenosylcobalamin (AdoCbl). There are three distinct complementation classes, cblA, B and D v2. cblA is caused by mutations in the MMAA gene (4q31.1-2); cblB by the MMAB gene (12q24.1); and cblD v2 by the MMADHC gene (2q23.2). The previously reported cblH disorder has been shown to be cblD v2. Diagnostic methods Diagnosis 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 diagnosis Differential 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 diagnosis Antenatal 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 counseling Transmission is autosomal recessive (1 in 4 recurrence risk/pregnancy). Management and treatment Treatment 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. Prognosis The 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. cblD v2 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 methylmalonic aciduria, cblb type. Affiliated tissues include brain, and 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 12.3
2 methylmalonic aciduria, cblb type 11.9
3 methylmalonic aciduria and homocystinuria, cblc type 11.7
4 methylmalonic aciduria and homocystinuria, cbld type 11.7
5 methylmalonic acidemia 10.7
6 isolated methylmalonic acidemia 10.7

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 13)
# 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 coma 58 31 hallmark (90%) Very frequent (99-80%) HP:0001259
7 lethargy 58 31 hallmark (90%) Very frequent (99-80%) HP:0001254
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
10 global developmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0001263
11 hyperammonemia 58 31 frequent (33%) Frequent (79-30%) HP:0001987
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

Drugs & Therapeutics for Adenosylcobalamin Deficiency

Search Clinical Trials , NIH Clinical Center for Adenosylcobalamin Deficiency

Genetic Tests for Adenosylcobalamin Deficiency

Anatomical Context for Adenosylcobalamin Deficiency

MalaCards organs/tissues related to Adenosylcobalamin Deficiency:


Publications for Adenosylcobalamin Deficiency

Articles related to Adenosylcobalamin Deficiency:

# Title Authors PMID Year
Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. 61 6
15523652 2004
Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies. 6
24813872 2015
Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type. 6
20556797 2010
Isolated Methylmalonic Acidemia 6
20301409 2005
Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. 6
12471062 2002
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
The cause of multiple sclerosis is autoimmune attack of adenosyltransferase thereby limiting adenosylcobalamin production. 61
29150289 2017
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
Accumulation of odd-numbered long-chain fatty acids in fetuses and neonates with inherited disorders of propionate metabolism. 61
1852536 1991
New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria. 61
3725502 1986

Variations for Adenosylcobalamin Deficiency

Expression for Adenosylcobalamin Deficiency

Search GEO for disease gene expression data for Adenosylcobalamin Deficiency.

Pathways for Adenosylcobalamin Deficiency

GO Terms for Adenosylcobalamin Deficiency

Sources for Adenosylcobalamin Deficiency

9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
31 HPO
32 ICD10
33 ICD10 via Orphanet
37 LifeMap
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
54 Novoseek
57 OMIM via Orphanet
61 PubMed
70 Tocris
72 UMLS via Orphanet
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