MCID: VTM024
MIFTS: 27

Vitamin B12-Responsive Methylmalonic Acidemia

Categories: Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Vitamin B12-Responsive Methylmalonic Acidemia

MalaCards integrated aliases for Vitamin B12-Responsive Methylmalonic Acidemia:

Name: Vitamin B12-Responsive Methylmalonic Acidemia 53 59
Vitamin B12-Responsive Methylmalonic Aciduria 53 59
Adenosylcobalamin Deficiency 53 59
Adenosylcobalamin Synthesis Defect 73

Characteristics:

Orphanet epidemiological data:

59
vitamin b12-responsive methylmalonic acidemia
Inheritance: Autosomal recessive; Age of onset: Childhood;

Classifications:



Summaries for Vitamin B12-Responsive Methylmalonic Acidemia

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 28Disease definitionVitamin B12-responsive methylmalonic acidemia (MA) is 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 (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 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 (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 : Vitamin B12-Responsive Methylmalonic Acidemia, also known as vitamin b12-responsive methylmalonic aciduria, is related to methylmalonic aciduria due to methylmalonyl-coa mutase deficiency and methylmalonic aciduria, cbla type. An important gene associated with Vitamin B12-Responsive Methylmalonic Acidemia is MMAA (Metabolism Of Cobalamin Associated A), and among its related pathways/superpathways are Metabolism of water-soluble vitamins and cofactors and Diseases of metabolism. Affiliated tissues include brain, and related phenotypes are intellectual disability and muscular hypotonia

Related Diseases for Vitamin B12-Responsive Methylmalonic Acidemia

Diseases related to Vitamin B12-Responsive Methylmalonic Acidemia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria due to methylmalonyl-coa mutase deficiency 30.5 MMAA MTR
2 methylmalonic aciduria, cbla type 11.8
3 methylmalonic aciduria, cblb type 11.7
4 methylmalonic aciduria and homocystinuria, cblc type 11.5
5 methylmalonic aciduria and homocystinuria, cbld type 11.5
6 transcobalamin ii deficiency 9.8 MMAA MTR
7 amino acid metabolic disorder 9.8 MMAA MTR

Graphical network of the top 20 diseases related to Vitamin B12-Responsive Methylmalonic Acidemia:



Diseases related to Vitamin B12-Responsive Methylmalonic Acidemia

Symptoms & Phenotypes for Vitamin B12-Responsive Methylmalonic Acidemia

Human phenotypes related to Vitamin B12-Responsive Methylmalonic Acidemia:

59 32 (show all 13)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 59 32 frequent (33%) Frequent (79-30%) HP:0001249
2 muscular hypotonia 59 32 frequent (33%) Frequent (79-30%) HP:0001252
3 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
4 nausea and vomiting 59 32 hallmark (90%) Very frequent (99-80%) HP:0002017
5 respiratory insufficiency 59 32 hallmark (90%) Very frequent (99-80%) HP:0002093
6 global developmental delay 59 32 frequent (33%) Frequent (79-30%) HP:0001263
7 hepatomegaly 59 32 hallmark (90%) Very frequent (99-80%) HP:0002240
8 renal insufficiency 59 32 occasional (7.5%) Occasional (29-5%) HP:0000083
9 dehydration 59 32 hallmark (90%) Very frequent (99-80%) HP:0001944
10 anemia 59 32 occasional (7.5%) Occasional (29-5%) HP:0001903
11 coma 59 32 hallmark (90%) Very frequent (99-80%) HP:0001259
12 hyperammonemia 59 32 frequent (33%) Frequent (79-30%) HP:0001987
13 lethargy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001254

Drugs & Therapeutics for Vitamin B12-Responsive Methylmalonic Acidemia

Search Clinical Trials , NIH Clinical Center for Vitamin B12-Responsive Methylmalonic Acidemia

Genetic Tests for Vitamin B12-Responsive Methylmalonic Acidemia

Anatomical Context for Vitamin B12-Responsive Methylmalonic Acidemia

MalaCards organs/tissues related to Vitamin B12-Responsive Methylmalonic Acidemia:

41
Brain

Publications for Vitamin B12-Responsive Methylmalonic Acidemia

Articles related to Vitamin B12-Responsive Methylmalonic Acidemia:

# Title Authors Year
1
Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia. ( 28536607 )
2016
2
Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. ( 12438653 )
2002
3
Prenatal treatment of a patient with vitamin B12-responsive methylmalonic acidemia. ( 2246694 )
1990
4
Long-term management of a patient with vitamin B12-responsive methylmalonic acidemia. ( 7359235 )
1980
5
Prenatal therapy of a patient with vitamin-B12-responsive methylmalonic acidemia. ( 239344 )
1975

Variations for Vitamin B12-Responsive Methylmalonic Acidemia

Expression for Vitamin B12-Responsive Methylmalonic Acidemia

Search GEO for disease gene expression data for Vitamin B12-Responsive Methylmalonic Acidemia.

Pathways for Vitamin B12-Responsive Methylmalonic Acidemia

Pathways related to Vitamin B12-Responsive Methylmalonic Acidemia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.76 MMAA MTR
2
Show member pathways
10.92 MMAA MTR
3 9.95 MMAA MTR

GO Terms for Vitamin B12-Responsive Methylmalonic Acidemia

Biological processes related to Vitamin B12-Responsive Methylmalonic Acidemia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cobalamin metabolic process GO:0009235 8.62 MMAA MTR

Sources for Vitamin B12-Responsive Methylmalonic Acidemia

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58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
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73 UMLS
74 UMLS via Orphanet
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