MCID: MTH079
MIFTS: 22

Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Categories: Genetic diseases, Rare diseases, Metabolic diseases, Blood diseases, Neuronal diseases, Mental diseases

Aliases & Classifications for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

MalaCards integrated aliases for Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

Name: Methylmalonic Acidemia and Homocysteinemia, Cblx Type 57 53
Mental Retardation, X-Linked 3 57 75 13 73
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cblx 53 59
Methylmalonic Acidemia with Homocystinuria, Type Cblx 53 59
Methylmalonic Aciduria with Homocystinuria, Type Cblx 53 59
Mental Retardation 3, X-Linked 29 6
Mrx3 57 75
Methylmalonic Acidemia and Homocysteinemia Type Cblx 53
Mental Retardation Non-Syndromic X-Linked 3 75
Mental Retardation, X-Linked 3; Mrx3 57
Mental Retardation, X-Linked, Type 3 40
Intellectual Disability, X-Linked 3 53

Characteristics:

Orphanet epidemiological data:

59
methylmalonic acidemia with homocystinuria, type cblx
Inheritance: X-linked recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Miscellaneous:
onset in infancy

Inheritance:
x-linked recessive


HPO:

32
methylmalonic acidemia and homocysteinemia, cblx type:
Onset and clinical course infantile onset
Inheritance x-linked recessive inheritance


Classifications:



Summaries for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

NIH Rare Diseases : 53 Methylmalonic acidemia and homocysteinemia type cblX, is an inborn error of vitamin B12 (cobalamin) metabolism in which the body is unable to break down (metabolize) certain proteins and fats properly. It is characterized by severe delays of motor (movement) and neurological (brain) development starting in infancy. Defects in cobalamin metabolism are characterized by a buildup of methylmalonic acid and/or homocysteine in the blood and urine. There are several other types of combined methylmalonic acidemia and homocysteinemia disorders, including cblC, cblD, cblF and cblJ. Signs and symptoms of methylmalonic acidemia and homocysteinemia type cblX may include difficulties with weight gain (failure to thrive), intellectual disability, and intractable (uncontrolled) epilepsy. Additional features may include a very small head (microcephaly), brain malformations, and movement disorders. This condition is caused by mutations in the HCFC1 gene, is inherited in an X-linked recessive manner, and is usually seen in males. Mutations within the HCFC1 gene affect another gene known as MMACHC, which is related to the most common defect of cobalamin disorder, cblC. There is no cure for this condition. In general, individuals with methylmalonic acidemia and homocystinuria may respond to a combined treatment strategy including supplementation of nutrients, such as a hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine.

MalaCards based summary : Methylmalonic Acidemia and Homocysteinemia, Cblx Type, is also known as mental retardation, x-linked 3. An important gene associated with Methylmalonic Acidemia and Homocysteinemia, Cblx Type is HCFC1 (Host Cell Factor C1). Affiliated tissues include brain, and related phenotypes are intellectual disability and failure to thrive

OMIM : 57 Methylmalonic acidemia and homocysteinemia, cblX type, is an X-linked recessive metabolic disorder characterized by severely delayed psychomotor development apparent in infancy. It is associated with failure to thrive, mental retardation, and intractable epilepsy. Additional features may include microcephaly and choreoathetosis (summary by Yu et al., 2013). (309541)

UniProtKB/Swiss-Prot : 75 Mental retardation, X-linked 3: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.

Related Diseases for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Symptoms & Phenotypes for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Symptoms via clinical synopsis from OMIM:

57
Growth Other:
failure to thrive

Growth Height:
short stature

Neurologic Central Nervous System:
hypsarrhythmia
hypotonia
mental retardation
seizures, intractable
severely delayed psychomotor development
more
Head And Neck Head:
microcephaly
brachycephaly

Laboratory Abnormalities:
methylmalonic aciduria
methylmalonic acidemia
homocystinuria (in some patients)
homocysteinemia (in some patients)


Clinical features from OMIM:

309541

Human phenotypes related to Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

32 (show all 12)
# Description HPO Frequency HPO Source Accession
1 intellectual disability 32 HP:0001249
2 failure to thrive 32 HP:0001508
3 chorea 32 occasional (7.5%) HP:0002072
4 microcephaly 32 HP:0000252
5 short stature 32 HP:0004322
6 brachycephaly 32 HP:0000248
7 methylmalonic aciduria 32 HP:0012120
8 athetosis 32 occasional (7.5%) HP:0002305
9 generalized hypotonia 32 HP:0001290
10 hypsarrhythmia 32 HP:0002521
11 homocystinuria 32 occasional (7.5%) HP:0002156
12 methylmalonic acidemia 32 HP:0002912

Drugs & Therapeutics for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Search Clinical Trials , NIH Clinical Center for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Genetic Tests for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Genetic tests related to Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

# Genetic test Affiliating Genes
1 Mental Retardation 3, X-Linked 29 HCFC1

Anatomical Context for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

MalaCards organs/tissues related to Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

41
Brain

Publications for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

Variations for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

UniProtKB/Swiss-Prot genetic disease variations for Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

75
# Symbol AA change Variation ID SNP ID
1 HCFC1 p.Ser225Asn VAR_069098 rs318240758

ClinVar genetic disease variations for Methylmalonic Acidemia and Homocysteinemia, Cblx Type:

6
(show all 33)
# Gene Variation Type Significance SNP ID Assembly Location
1 HCFC1 NM_005334.2(HCFC1): c.-970T> C single nucleotide variant Pathogenic rs398122908 GRCh37 Chromosome X, 153237261: 153237261
2 HCFC1 NM_005334.2(HCFC1): c.-970T> C single nucleotide variant Pathogenic rs398122908 GRCh38 Chromosome X, 153971810: 153971810
3 HCFC1 NM_005334.2(HCFC1): c.-970T> C single nucleotide variant Pathogenic rs398122908 NCBI36 Chromosome X, 152890455: 152890455
4 HCFC1 NM_005334.2(HCFC1): c.674G> A (p.Ser225Asn) single nucleotide variant Pathogenic rs318240758 GRCh37 Chromosome X, 153228714: 153228714
5 HCFC1 NM_005334.2(HCFC1): c.674G> A (p.Ser225Asn) single nucleotide variant Pathogenic rs318240758 GRCh38 Chromosome X, 153963263: 153963263
6 HCFC1 NM_005334.2(HCFC1): c.344C> T (p.Ala115Val) single nucleotide variant Pathogenic rs397515485 GRCh37 Chromosome X, 153229734: 153229734
7 HCFC1 NM_005334.2(HCFC1): c.344C> T (p.Ala115Val) single nucleotide variant Pathogenic rs397515485 GRCh38 Chromosome X, 153964283: 153964283
8 HCFC1 NM_005334.2(HCFC1): c.218C> T (p.Ala73Val) single nucleotide variant Pathogenic rs397515486 GRCh37 Chromosome X, 153230153: 153230153
9 HCFC1 NM_005334.2(HCFC1): c.218C> T (p.Ala73Val) single nucleotide variant Pathogenic rs397515486 GRCh38 Chromosome X, 153964702: 153964702
10 HCFC1 NM_005334.2(HCFC1): c.217G> A (p.Ala73Thr) single nucleotide variant Pathogenic rs397515487 GRCh37 Chromosome X, 153230154: 153230154
11 HCFC1 NM_005334.2(HCFC1): c.217G> A (p.Ala73Thr) single nucleotide variant Pathogenic rs397515487 GRCh38 Chromosome X, 153964703: 153964703
12 HCFC1 NM_005334.2(HCFC1): c.2109G> A (p.Thr703=) single nucleotide variant Benign/Likely benign rs3027888 GRCh37 Chromosome X, 153223257: 153223257
13 HCFC1 NM_005334.2(HCFC1): c.2109G> A (p.Thr703=) single nucleotide variant Benign/Likely benign rs3027888 GRCh38 Chromosome X, 153957806: 153957806
14 HCFC1 NM_005334.2(HCFC1): c.2590G> A (p.Ala864Thr) single nucleotide variant Likely benign rs190023981 GRCh37 Chromosome X, 153222121: 153222121
15 HCFC1 NM_005334.2(HCFC1): c.2590G> A (p.Ala864Thr) single nucleotide variant Likely benign rs190023981 GRCh38 Chromosome X, 153956670: 153956670
16 HCFC1 NM_005334.2(HCFC1): c.3492C> T (p.Ser1164=) single nucleotide variant Conflicting interpretations of pathogenicity rs376049260 GRCh38 Chromosome X, 153954907: 153954907
17 HCFC1 NM_005334.2(HCFC1): c.3492C> T (p.Ser1164=) single nucleotide variant Conflicting interpretations of pathogenicity rs376049260 GRCh37 Chromosome X, 153220358: 153220358
18 HCFC1 NM_005334.2(HCFC1): c.5048C> G (p.Pro1683Arg) single nucleotide variant Pathogenic rs869312686 GRCh38 Chromosome X, 153952053: 153952053
19 HCFC1 NM_005334.2(HCFC1): c.5048C> G (p.Pro1683Arg) single nucleotide variant Pathogenic rs869312686 GRCh37 Chromosome X, 153217504: 153217504
20 HCFC1 NM_005334.2(HCFC1): c.1429G> A (p.Ala477Thr) single nucleotide variant Uncertain significance rs782010359 GRCh37 Chromosome X, 153225268: 153225268
21 HCFC1 NM_005334.2(HCFC1): c.1429G> A (p.Ala477Thr) single nucleotide variant Uncertain significance rs782010359 GRCh38 Chromosome X, 153959817: 153959817
22 HCFC1 NM_005334.2(HCFC1): c.4442C> T (p.Thr1481Met) single nucleotide variant Benign/Likely benign rs199798029 GRCh37 Chromosome X, 153219113: 153219113
23 HCFC1 NM_005334.2(HCFC1): c.4442C> T (p.Thr1481Met) single nucleotide variant Benign/Likely benign rs199798029 GRCh38 Chromosome X, 153953662: 153953662
24 HCFC1 NM_005334.2(HCFC1): c.2382C> A (p.Ser794=) single nucleotide variant Benign rs1051151 GRCh37 Chromosome X, 153222483: 153222483
25 HCFC1 NM_005334.2(HCFC1): c.2382C> A (p.Ser794=) single nucleotide variant Benign rs1051151 GRCh38 Chromosome X, 153957032: 153957032
26 THAP11 NM_020457.2(THAP11): c.240C> G (p.Phe80Leu) single nucleotide variant Likely pathogenic rs188675529 GRCh37 Chromosome 16, 67876697: 67876697
27 THAP11 NM_020457.2(THAP11): c.240C> G (p.Phe80Leu) single nucleotide variant Likely pathogenic rs188675529 GRCh38 Chromosome 16, 67842794: 67842794
28 HCFC1 NM_005334.2(HCFC1): c.5601C> T (p.Ala1867=) single nucleotide variant Benign rs144160012 GRCh37 Chromosome X, 153216366: 153216366
29 HCFC1 NM_005334.2(HCFC1): c.5601C> T (p.Ala1867=) single nucleotide variant Benign rs144160012 GRCh38 Chromosome X, 153950915: 153950915
30 HCFC1 NM_005334.2(HCFC1): c.2232G> A (p.Ala744=) single nucleotide variant Likely benign GRCh37 Chromosome X, 153222886: 153222886
31 HCFC1 NM_005334.2(HCFC1): c.2232G> A (p.Ala744=) single nucleotide variant Likely benign GRCh38 Chromosome X, 153957435: 153957435
32 HCFC1 NM_005334.2(HCFC1): c.3853G> A (p.Val1285Met) single nucleotide variant Benign rs199611189 GRCh38 Chromosome X, 153954546: 153954546
33 HCFC1 NM_005334.2(HCFC1): c.3853G> A (p.Val1285Met) single nucleotide variant Benign rs199611189 GRCh37 Chromosome X, 153219997: 153219997

Expression for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

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Pathways for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

GO Terms for Methylmalonic Acidemia and Homocysteinemia, Cblx Type

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