Vitamin B12-unresponsive methylmalonic acidemia

General Information (adopted from Orphanet):

Synonyms, Signs: Vitamin B12-unresponsive methylmalonic aciduria
METHYLMALONIC ACIDURIA, mut TYPE METHYLMALONIC ACIDURIA, mut(0) TYPE, INCLUDED
METHYLMALONIC ACIDURIA, mut(-) TYPE, INCLUDED
METHYLMALONIC ACIDEMIA DUE TO METHYLMALONYL-CoA MUTASE DEFICIENCY MMA DUE TO MCM DEFICIENCY
Number of Symptoms 49
OrphanetNr: 27
OMIM Id: 251000
ICD-10: E71.1
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Methylmalonic acidemia without homocystinuria
 -Rare genetic disease
Nephropathy secondary to a storage or other metabolic disease
 -Rare genetic disease
 -Rare renal disease

Symptom Information: Sort by abundance 

1
 (HPO:0002017) Nausea and vomiting Very frequent [Orphanet] 134 / 7739
2
 (HPO:0002013) Vomiting 191 / 7739
3
 (HPO:0011695) Cerebellar hemorrhage rare [HPO:skoehler] 6 / 7739
4
 (HPO:0002093) Respiratory insufficiency Very frequent [Orphanet] 410 / 7739
5
 (HPO:0005979) Metabolic ketoacidosis 4 / 7739
6
 (HPO:0001508) Failure to thrive 454 / 7739
7
 (HPO:0002154) Hyperglycinemia 12 / 7739
8
 (HPO:0012120) Methylmalonic aciduria 20 / 7739
9
 (HPO:0002912) Methylmalonic acidemia 14 / 7739
10
 (HPO:0001638) Cardiomyopathy Occasional [Orphanet] 192 / 7739
11
 (HPO:0001903) Anemia Occasional [Orphanet] 289 / 7739
12
 (HPO:0001944) Dehydration Very frequent [Orphanet] 59 / 7739
13
 (HPO:0010978) Abnormality of immune system physiology Occasional [Orphanet] 148 / 7739
14
 (HPO:0001882) Leukopenia Frequent [Orphanet] 51 / 7739
15
 (HPO:0001987) Hyperammonemia Occasional [Orphanet] 50 / 7739
16
 (HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
17
 (HPO:0008947) Infantile muscular hypotonia 482 / 7739
18
 (HPO:0010547) Muscle flaccidity 466 / 7739
19
 (HPO:0004305) Involuntary movements Occasional [Orphanet] 50 / 7739
20
 (HPO:0001324) Muscle weakness 859 / 7739
21
 (HPO:0002066) Gait ataxia Occasional [Orphanet] 327 / 7739
22
 (HPO:0004374) Hemiplegia/hemiparesis Occasional [Orphanet] 158 / 7739
23
 (HPO:0001263) Global developmental delay 853 / 7739
24
 (HPO:0001254) Lethargy 104 / 7739
25
 (HPO:0001259) Coma 65 / 7739
26
 (HPO:0002167) Neurological speech impairment 308 / 7739
27
 (HPO:0004372) Reduced consciousness/confusion Very frequent [Orphanet] 73 / 7739
28
 (HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
29
 (HPO:0002240) Hepatomegaly Frequent [Orphanet] 467 / 7739
30
 (HPO:0001733) Pancreatitis Occasional [Orphanet] 46 / 7739
31
 (HPO:0001970) Tubulointerstitial nephritis Occasional [Orphanet] 27 / 7739
32
 (HPO:0003774) Stage 5 chronic kidney disease 78 / 7739
33
 (HPO:0000083) Renal insufficiency Occasional [Orphanet] 232 / 7739
34
 (HPO:0000124) Renal tubular dysfunction Occasional [Orphanet] 46 / 7739
35
 (HPO:0001873) Thrombocytopenia Frequent [Orphanet] 224 / 7739
36
 (HPO:0002453) Abnormality of the globus pallidus 4 / 7739
37
 (HPO:0012795) Abnormality of the optic disc Occasional [Orphanet] 187 / 7739
38
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
39
 (HPO:0001522) Death in infancy Very frequent [Orphanet] 275 / 7739
40
 (HPO:0002188) Delayed CNS myelination 16 / 7739
41
 (HPO:0012758) Neurodevelopmental delay Frequent [Orphanet] 949 / 7739
42
 (OMIM) Delay in myelination 3 / 7739
43
 (OMIM) Ischemic stroke in the basal ganglia (rare) 4 / 7739
44
 (OMIM) Low plasma free and total carnitine 3 / 7739
45
 (OMIM) Methylmalonyl-CoA mutase deficiency 3 / 7739
46
 (OMIM) Neonatal or infantile metabolic ketoacidosis 3 / 7739
47
 (OMIM) Normal serum cobalamin 7 / 7739
48
 (OMIM) Recurrent episodes of vomiting 3 / 7739
49
 (OMIM) Severe involvement of globus pallidus 3 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Methylmalonic aciduria is a genetically heterogeneous disorder of methylmalonate and cobalamin (cbl; vitamin B12) metabolism. Isolated methylmalonic aciduria is found in patients with mutations in the MUT gene causing partial, mut(-), or complete, mut(0), enzyme deficiency. This form ...
Diagnosis OMIM Wilkemeyer et al. (1991) showed that the mut and cbl forms of MMA can be differentiated not only by somatic cell complementation but also by DNA-mediated gene transfer of a methylmalonyl CoA mutase cDNA clone. Transfer of the ...
Clinical Description OMIM The clinical spectrum of methylmalonic aciduria is wide, ranging from a benign condition (Ledley et al., 1984) to fatal neonatal disease (Matsui et al., 1983).

Oberholzer et al. (1967) reported an inborn error of metabolism characterized ...
Molecular genetics OMIM In a patient with MMA mut(0), defined as having no residual enzyme activity, Jansen and Ledley (1990) identified compound heterozygosity for 2 mutations in the MUT gene (609058.0001 and 609058.0002).

In a patient with MMA mut(-), ...