MCID: MTH013
MIFTS: 23

Methylmalonate Semialdehyde Dehydrogenase Deficiency

Categories: Genetic diseases, Metabolic diseases, Rare diseases

Aliases & Classifications for Methylmalonate Semialdehyde Dehydrogenase Deficiency

MalaCards integrated aliases for Methylmalonate Semialdehyde Dehydrogenase Deficiency:

Name: Methylmalonate Semialdehyde Dehydrogenase Deficiency 57 75 29 13 6 40 73
Mmsdh Deficiency 57 75
Mmsdhd 57 75
Developmental Delay Due to Methylmalonate Semialdehyde Dehydrogenase Deficiency 59
Developmental Delay Due to Aldh6a1 Deficiency 59
Developmental Delay Due to Mmsdh Deficiency 59

Characteristics:

Orphanet epidemiological data:

59
developmental delay due to methylmalonate semialdehyde dehydrogenase deficiency
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
highly variable phenotype
onset in infancy or early childhood
dysmorphic facial features are variable
four unrelated patients have been reported (last curated august 2015)
one patient was asymptomatic and detected by neonatal screening


HPO:

32
methylmalonate semialdehyde dehydrogenase deficiency:
Onset and clinical course phenotypic variability
Inheritance autosomal recessive inheritance


Classifications:

Orphanet: 59  
Inborn errors of metabolism


Summaries for Methylmalonate Semialdehyde Dehydrogenase Deficiency

OMIM : 57 Methylmalonate semialdehyde dehydrogenase deficiency is a rare autosomal recessive inborn error of metabolism with a highly variable phenotype. Some patients may be asymptomatic, whereas others show global developmental delay, nonspecific dysmorphic features, and delayed myelination on brain imaging. Laboratory studies typically show increased urinary 3-hydroxyisobutyric acid, although additional metabolic abnormalities may also be observed (summary by Marcadier et al., 2013). (614105)

MalaCards based summary : Methylmalonate Semialdehyde Dehydrogenase Deficiency, is also known as mmsdh deficiency. An important gene associated with Methylmalonate Semialdehyde Dehydrogenase Deficiency is ALDH6A1 (Aldehyde Dehydrogenase 6 Family Member A1). Affiliated tissues include brain, and related phenotypes are high palate and microcephaly

UniProtKB/Swiss-Prot : 75 Methylmalonate semialdehyde dehydrogenase deficiency: A metabolic disorder characterized by elevated beta-alanine, 3- hydroxypropionic acid, and both isomers of 3-amino and 3- hydroxyisobutyric acids in urine organic acids.

Related Diseases for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Symptoms & Phenotypes for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Symptoms via clinical synopsis from OMIM:

57
Metabolic Features:
metabolic acidosis
metabolic decompensation during febrile illness (patient b)

Abdomen Gastrointestinal:
poor feeding (patient a)

Head And Neck Face:
dysmorphic facial features, variable
long philtrum (patient b)
tall forehead (patient c)
frontal bossing (patient c)

Head And Neck Nose:
short nose (patients a and c)
depressed nasal bridge (patient a)
bulbous nose (patient b)
hypoplastic nasae alae (patient b)

Muscle Soft Tissue:
hypotonia (patients a and c)

Neurologic Central Nervous System:
delayed psychomotor development
dystonia (patient c)
delayed myelination (patients a and c)
thin corpus callosum (patients a and c)

Head And Neck Head:
microcephaly (patient a, b,)

Head And Neck Eyes:
cataracts (patient a)
microphthalmia (patient a)
downslanting palpebral fissures (patient a)
epicanthal folds (patient c)
hypertelorism (patient c)

Head And Neck Mouth:
high-arched palate (patient c)
tented mouth (patient c)

Laboratory Abnormalities:
increased urinary 3-hydroxyisobutyric acid
increased urinary 3-aminoisobutyric acid
increased urinary beta-alanine
increased urinary 3-hydroxypropionate (in some patients)
increased lactate (in some patients) increased urinary methylmalonic acid (in some patients)


Clinical features from OMIM:

614105

Human phenotypes related to Methylmalonate Semialdehyde Dehydrogenase Deficiency:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 high palate 32 HP:0000218
2 microcephaly 32 HP:0000252
3 epicanthus 32 HP:0000286
4 hypertelorism 32 HP:0000316
5 long philtrum 32 HP:0000343
6 high forehead 32 HP:0000348
7 bulbous nose 32 HP:0000414
8 downslanted palpebral fissures 32 HP:0000494
9 cataract 32 HP:0000518
10 microphthalmia 32 HP:0000568
11 global developmental delay 32 HP:0001263
12 generalized hypotonia 32 HP:0001290
13 dystonia 32 HP:0001332
14 metabolic acidosis 32 HP:0001942
15 abnormal facial shape 32 frequent (33%) HP:0001999
16 frontal bossing 32 HP:0002007
17 hypoplasia of the corpus callosum 32 HP:0002079
18 short nose 32 HP:0003196
19 depressed nasal bridge 32 HP:0005280
20 tented upper lip vermilion 32 HP:0010804
21 feeding difficulties 32 HP:0011968
22 delayed myelination 32 HP:0012448

Drugs & Therapeutics for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Search Clinical Trials , NIH Clinical Center for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Genetic Tests for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Genetic tests related to Methylmalonate Semialdehyde Dehydrogenase Deficiency:

# Genetic test Affiliating Genes
1 Methylmalonate Semialdehyde Dehydrogenase Deficiency 29 ALDH6A1

Anatomical Context for Methylmalonate Semialdehyde Dehydrogenase Deficiency

MalaCards organs/tissues related to Methylmalonate Semialdehyde Dehydrogenase Deficiency:

41
Brain

Publications for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Articles related to Methylmalonate Semialdehyde Dehydrogenase Deficiency:

# Title Authors Year
1
Molecular characterization of methylmalonate semialdehyde dehydrogenase deficiency. ( 10947204 )
2000

Variations for Methylmalonate Semialdehyde Dehydrogenase Deficiency

UniProtKB/Swiss-Prot genetic disease variations for Methylmalonate Semialdehyde Dehydrogenase Deficiency:

75
# Symbol AA change Variation ID SNP ID
1 ALDH6A1 p.Gly446Arg VAR_010244 rs72552258

ClinVar genetic disease variations for Methylmalonate Semialdehyde Dehydrogenase Deficiency:

6
(show top 50) (show all 72)
# Gene Variation Type Significance SNP ID Assembly Location
1 ALDH6A1 NM_005589.3(ALDH6A1): c.1336G> A (p.Gly446Arg) single nucleotide variant Pathogenic rs72552258 GRCh37 Chromosome 14, 74531952: 74531952
2 ALDH6A1 NM_005589.3(ALDH6A1): c.1336G> A (p.Gly446Arg) single nucleotide variant Pathogenic rs72552258 GRCh38 Chromosome 14, 74065249: 74065249
3 ALDH6A1 NM_005589.3(ALDH6A1): c.785C> A (p.Ser262Tyr) single nucleotide variant Pathogenic rs879255579 GRCh38 Chromosome 14, 74068927: 74068927
4 ALDH6A1 NM_005589.3(ALDH6A1): c.785C> A (p.Ser262Tyr) single nucleotide variant Pathogenic rs879255579 GRCh37 Chromosome 14, 74535630: 74535630
5 ALDH6A1 NM_005589.3(ALDH6A1): c.184C> T (p.Pro62Ser) single nucleotide variant Pathogenic rs796065046 GRCh37 Chromosome 14, 74539242: 74539242
6 ALDH6A1 NM_005589.3(ALDH6A1): c.184C> T (p.Pro62Ser) single nucleotide variant Pathogenic rs796065046 GRCh38 Chromosome 14, 74072539: 74072539
7 ALDH6A1 NM_005589.3(ALDH6A1): c.1603C> T (p.Arg535Cys) single nucleotide variant Uncertain significance rs367863044 GRCh37 Chromosome 14, 74527350: 74527350
8 ALDH6A1 NM_005589.3(ALDH6A1): c.1603C> T (p.Arg535Cys) single nucleotide variant Uncertain significance rs367863044 GRCh38 Chromosome 14, 74060647: 74060647
9 ALDH6A1 NM_005589.3(ALDH6A1): c.514T> C (p.Tyr172His) single nucleotide variant Pathogenic rs869320672 GRCh37 Chromosome 14, 74538114: 74538114
10 ALDH6A1 NM_005589.3(ALDH6A1): c.514T> C (p.Tyr172His) single nucleotide variant Pathogenic rs869320672 GRCh38 Chromosome 14, 74071411: 74071411
11 ALDH6A1 NM_005589.3(ALDH6A1): c.*403T> C single nucleotide variant Benign rs1135885 GRCh38 Chromosome 14, 74060239: 74060239
12 ALDH6A1 NM_005589.3(ALDH6A1): c.*403T> C single nucleotide variant Benign rs1135885 GRCh37 Chromosome 14, 74526942: 74526942
13 ALDH6A1 NM_005589.3(ALDH6A1): c.*142C> T single nucleotide variant Benign rs8017248 GRCh37 Chromosome 14, 74527203: 74527203
14 ALDH6A1 NM_005589.3(ALDH6A1): c.*142C> T single nucleotide variant Benign rs8017248 GRCh38 Chromosome 14, 74060500: 74060500
15 ALDH6A1 NM_005589.3(ALDH6A1): c.*43C> G single nucleotide variant Uncertain significance rs545399557 GRCh37 Chromosome 14, 74527302: 74527302
16 ALDH6A1 NM_005589.3(ALDH6A1): c.*43C> G single nucleotide variant Uncertain significance rs545399557 GRCh38 Chromosome 14, 74060599: 74060599
17 ALDH6A1 NM_005589.3(ALDH6A1): c.1479A> G (p.Gly493=) single nucleotide variant Uncertain significance rs886050730 GRCh37 Chromosome 14, 74531549: 74531549
18 ALDH6A1 NM_005589.3(ALDH6A1): c.1479A> G (p.Gly493=) single nucleotide variant Uncertain significance rs886050730 GRCh38 Chromosome 14, 74064846: 74064846
19 ALDH6A1 NM_005589.3(ALDH6A1): c.799G> A (p.Glu267Lys) single nucleotide variant Uncertain significance rs763810979 GRCh38 Chromosome 14, 74068913: 74068913
20 ALDH6A1 NM_005589.3(ALDH6A1): c.799G> A (p.Glu267Lys) single nucleotide variant Uncertain significance rs763810979 GRCh37 Chromosome 14, 74535616: 74535616
21 ALDH6A1 NM_005589.3(ALDH6A1): c.414A> G (p.Val138=) single nucleotide variant Likely benign rs4899491 GRCh38 Chromosome 14, 74071909: 74071909
22 ALDH6A1 NM_005589.3(ALDH6A1): c.414A> G (p.Val138=) single nucleotide variant Likely benign rs4899491 GRCh37 Chromosome 14, 74538612: 74538612
23 ALDH6A1 NM_005589.3(ALDH6A1): c.*433C> T single nucleotide variant Likely benign rs1135886 GRCh38 Chromosome 14, 74060209: 74060209
24 ALDH6A1 NM_005589.3(ALDH6A1): c.*433C> T single nucleotide variant Likely benign rs1135886 GRCh37 Chromosome 14, 74526912: 74526912
25 ALDH6A1 NM_005589.3(ALDH6A1): c.*403T> G single nucleotide variant Uncertain significance rs1135885 GRCh38 Chromosome 14, 74060239: 74060239
26 ALDH6A1 NM_005589.3(ALDH6A1): c.*403T> G single nucleotide variant Uncertain significance rs1135885 GRCh37 Chromosome 14, 74526942: 74526942
27 ALDH6A1 NM_005589.3(ALDH6A1): c.*234C> T single nucleotide variant Uncertain significance rs117311919 GRCh37 Chromosome 14, 74527111: 74527111
28 ALDH6A1 NM_005589.3(ALDH6A1): c.*234C> T single nucleotide variant Uncertain significance rs117311919 GRCh38 Chromosome 14, 74060408: 74060408
29 ALDH6A1 NM_005589.3(ALDH6A1): c.1221C> G (p.Val407=) single nucleotide variant Uncertain significance rs756896845 GRCh37 Chromosome 14, 74533411: 74533411
30 ALDH6A1 NM_005589.3(ALDH6A1): c.1221C> G (p.Val407=) single nucleotide variant Uncertain significance rs756896845 GRCh38 Chromosome 14, 74066708: 74066708
31 ALDH6A1 NM_005589.3(ALDH6A1): c.853-3dupT duplication Likely benign rs528185481 GRCh37 Chromosome 14, 74534275: 74534275
32 ALDH6A1 NM_005589.3(ALDH6A1): c.853-3dupT duplication Likely benign rs528185481 GRCh38 Chromosome 14, 74067572: 74067572
33 ALDH6A1 NM_005589.3(ALDH6A1): c.112-14T> G single nucleotide variant Uncertain significance rs886050732 GRCh38 Chromosome 14, 74072625: 74072625
34 ALDH6A1 NM_005589.3(ALDH6A1): c.112-14T> G single nucleotide variant Uncertain significance rs886050732 GRCh37 Chromosome 14, 74539328: 74539328
35 ALDH6A1 NM_005589.3(ALDH6A1): c.-59A> C single nucleotide variant Uncertain significance rs886050733 GRCh38 Chromosome 14, 74084453: 74084453
36 ALDH6A1 NM_005589.3(ALDH6A1): c.-59A> C single nucleotide variant Uncertain significance rs886050733 GRCh37 Chromosome 14, 74551156: 74551156
37 ALDH6A1 NM_005589.3(ALDH6A1): c.*377C> A single nucleotide variant Uncertain significance rs886050729 GRCh37 Chromosome 14, 74526968: 74526968
38 ALDH6A1 NM_005589.3(ALDH6A1): c.*377C> A single nucleotide variant Uncertain significance rs886050729 GRCh38 Chromosome 14, 74060265: 74060265
39 ALDH6A1 NM_005589.3(ALDH6A1): c.*309G> A single nucleotide variant Uncertain significance rs150950908 GRCh37 Chromosome 14, 74527036: 74527036
40 ALDH6A1 NM_005589.3(ALDH6A1): c.*309G> A single nucleotide variant Uncertain significance rs150950908 GRCh38 Chromosome 14, 74060333: 74060333
41 ALDH6A1 NM_005589.3(ALDH6A1): c.1557_1559delAGA (p.Glu519del) deletion Uncertain significance rs771596943 GRCh37 Chromosome 14, 74527394: 74527396
42 ALDH6A1 NM_005589.3(ALDH6A1): c.1557_1559delAGA (p.Glu519del) deletion Uncertain significance rs771596943 GRCh38 Chromosome 14, 74060691: 74060693
43 ALDH6A1 NM_005589.3(ALDH6A1): c.1397T> C (p.Val466Ala) single nucleotide variant Uncertain significance rs764356053 GRCh37 Chromosome 14, 74531891: 74531891
44 ALDH6A1 NM_005589.3(ALDH6A1): c.1397T> C (p.Val466Ala) single nucleotide variant Uncertain significance rs764356053 GRCh38 Chromosome 14, 74065188: 74065188
45 ALDH6A1 NM_005589.3(ALDH6A1): c.731-12T> C single nucleotide variant Uncertain significance rs10146187 GRCh38 Chromosome 14, 74068993: 74068993
46 ALDH6A1 NM_005589.3(ALDH6A1): c.731-12T> C single nucleotide variant Uncertain significance rs10146187 GRCh37 Chromosome 14, 74535696: 74535696
47 ALDH6A1 NM_005589.3(ALDH6A1): c.189C> T (p.Ala63=) single nucleotide variant Uncertain significance rs886050731 GRCh38 Chromosome 14, 74072362: 74072362
48 ALDH6A1 NM_005589.3(ALDH6A1): c.189C> T (p.Ala63=) single nucleotide variant Uncertain significance rs886050731 GRCh37 Chromosome 14, 74539065: 74539065
49 ALDH6A1 NM_005589.3(ALDH6A1): c.112-11_112-8dupGTTT duplication Uncertain significance rs551611189 GRCh38 Chromosome 14, 74072619: 74072622
50 ALDH6A1 NM_005589.3(ALDH6A1): c.112-11_112-8dupGTTT duplication Uncertain significance rs551611189 GRCh37 Chromosome 14, 74539322: 74539325

Expression for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Search GEO for disease gene expression data for Methylmalonate Semialdehyde Dehydrogenase Deficiency.

Pathways for Methylmalonate Semialdehyde Dehydrogenase Deficiency

GO Terms for Methylmalonate Semialdehyde Dehydrogenase Deficiency

Sources for Methylmalonate Semialdehyde Dehydrogenase Deficiency

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