MCID: VTM024
MIFTS: 24

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 72

Characteristics:

Orphanet epidemiological data:

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

Classifications:



External Ids:

ICD10 via Orphanet 34 E71.1
Orphanet 59 ORPHA28
UMLS 72 C0342720

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: 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 : Vitamin B12-Responsive Methylmalonic Acidemia, also known as vitamin b12-responsive methylmalonic aciduria, is related to methylmalonic aciduria, cbla type and methylmalonic aciduria, cblb 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 failure to thrive and nausea and vomiting

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, 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
7 transcobalamin ii deficiency 9.5 MTR MMAA
8 amino acid metabolic disorder 9.4 MTR MMAA
9 methylmalonic aciduria due to methylmalonyl-coa mutase deficiency 9.2 MTR MMAA

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

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:

(show all 13)
# Title Authors PMID Year
1
Mutations in the MMAA gene in patients with the cblA disorder of vitamin B12 metabolism. 38 71
15523652 2004
2
Identification of the gene responsible for the cblA complementation group of vitamin B12-responsive methylmalonic acidemia based on analysis of prokaryotic gene arrangements. 38 71
12438653 2002
3
Methylmalonic aciduria cblB type: characterization of two novel mutations and mitochondrial dysfunction studies. 71
24813872 2015
4
Functional and structural analysis of five mutations identified in methylmalonic aciduria cblB type. 71
20556797 2010
5
Isolated Methylmalonic Acidemia 71
20301409 2005
6
Identification of the gene responsible for the cblB complementation group of vitamin B12-dependent methylmalonic aciduria. 71
12471062 2002
7
Identification of a novel deletion in the MMAA gene in two Iranian siblings with vitamin B12-responsive methylmalonic acidemia. 38
28536607 2016
8
Urinary organic metabolite screening of children with influenza-associated encephalopathy for inborn errors of metabolism using GC/MS. 38
18262742 2008
9
Accumulation of odd-numbered long-chain fatty acids in fetuses and neonates with inherited disorders of propionate metabolism. 38
1852536 1991
10
Prenatal treatment of a patient with vitamin B12-responsive methylmalonic acidemia. 38
2246694 1990
11
New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria. 38
3725502 1986
12
Long-term management of a patient with vitamin B12-responsive methylmalonic acidemia. 38
7359235 1980
13
Prenatal therapy of a patient with vitamin-B12-responsive methylmalonic acidemia. 38
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 MTR MMAA
2
Show member pathways
10.92 MTR MMAA
3 9.95 MTR MMAA

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 MTR MMAA

Sources for Vitamin B12-Responsive Methylmalonic Acidemia

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