MAHCF
MCID: MTH056
MIFTS: 31

Methylmalonic Aciduria and Homocystinuria, Cblf Type (MAHCF)

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

Aliases & Classifications for Methylmalonic Aciduria and Homocystinuria, Cblf Type

MalaCards integrated aliases for Methylmalonic Aciduria and Homocystinuria, Cblf Type:

Name: Methylmalonic Aciduria and Homocystinuria, Cblf Type 57 75 29 13 6 73
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cblf 53 59
Methylmalonic Aciduria Due to Vitamin B12-Release Defect 57 75
Methylmalonic Aciduria with Homocystinuria, Type Cblf 53 59
Methylmalonic Acidemia with Homocystinuria Type Cblf 53 59
Vitamin B12 Lysosomal Release Defect 57 75
Cobalamin F Disease 57 75
Mahcf 57 75
Cblf 57 75
Aciduria, Methylmalonic, and Homocystinuria, Cblf Type 40
Methylmalonic Acidemia and Homocystinuria, Cblf Type 57
Methylmalonic Aciduria and Homocystinuria Type Cblf 12
Lysosomal Membrane Cobalamin Transporter Deficiency 59
Methylmalonic Acidemia and Homocystinuria Cblf Type 75
Cobalamin, Defect in Lysosomal Release of 57
Methylcobalamin Deficiency Tape F 75
Vitamin B12 Storage Disease 57
Vitamin B12 Storage Defect 75
Cobalamin F Disease; Cblf 57
Cobalamin F Deficiency 12
Cobalamin F Defect 59
Cblf Defect 59

Characteristics:

Orphanet epidemiological data:

59
methylmalonic acidemia with homocystinuria type cblf
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
responsive to vitamin b12 therapy
see also cblc


HPO:

32
methylmalonic aciduria and homocystinuria, cblf type:
Onset and clinical course infantile onset
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Methylmalonic Aciduria and Homocystinuria, Cblf Type

OMIM : 57 Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous disorder of cobalamin (cbl; vitamin B12) metabolism. The defect causes decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl), which results in decreased activity of the respective enzymes methylmalonyl-CoA mutase (MUT; 609058) and methyltetrahydrofolate:homocysteine methyltransferase, also known as methionine synthase (MTR; 156570). Different forms of the disorder have been classified according to complementation groups of cells in vitro: cblC (MAHCC; 277400), cblD (MAHCD; 277410), cblF, and cblJ (MAHCJ; 614857). (277380)

MalaCards based summary : Methylmalonic Aciduria and Homocystinuria, Cblf Type, also known as combined defect in adenosylcobalamin and methylcobalamin synthesis, type cblf, is related to methylmalonic aciduria and homocystinuria, cbld type and methylmalonic aciduria and homocystinuria, cblj type, and has symptoms including lethargy and exanthema. An important gene associated with Methylmalonic Aciduria and Homocystinuria, Cblf Type is LMBRD1 (LMBR1 Domain Containing 1). Affiliated tissues include skin, bone and bone marrow, and related phenotypes are seizures and ataxia

Disease Ontology : 12 A methylmalonic acidemia that is characterized by the accumulation of cobalamin in lysosomes which is then unable to synthesize the cofactors adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl).

NIH Rare Diseases : 53 Methylmalonic aciduria with homocystinuria cbl f is a form of methylmalonic acidemia with homocystinuria, an inborn error of vitamin B12 (cobalamin) metabolism that can cause the following signs and symptoms: megaloblastic anemia, lack of energy, growth delays, developmental delay, intellectual disability and seizures. The appearance of signs and symptoms can vary from birth to 11 years old. The disorder is caused by mutations in the LMBRD1 gene and is transmitted in an autosomal recessive manner. Treatment options include vitamin B12 injections and dietary management.

UniProtKB/Swiss-Prot : 75 Methylmalonic aciduria and homocystinuria, cblF type: An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). It is due to accumulation of free cobalamin in lysosomes, thus hindering its conversion to cofactors. Clinical features include developmental delay, stomatitis, glossitis, seizures and methylmalonic aciduria responsive to vitamin B12.

Related Diseases for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Graphical network of the top 20 diseases related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:



Diseases related to Methylmalonic Aciduria and Homocystinuria, Cblf Type

Symptoms & Phenotypes for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Symptoms via clinical synopsis from OMIM:

57
Head And Neck Ears:
low-set ears
small ears

Hematology:
pancytopenia
thrombocytopenia
neutropenia
megaloblastic anemia

Head And Neck Mouth:
glossitis
stomatitis
high-arched palate
thin upper lip

Head And Neck Eyes:
epicanthal folds

Skin Nails Hair Skin:
reticulate pigmented skin abnormalities
skin rashes

Growth Other:
failure to thrive

Neurologic Central Nervous System:
lethargy
developmental delay
hypotonia
impaired coordination

Laboratory Abnormalities:
methylmalonic aciduria
cystathioninuria
homocystinuria
homocystinemia
methylmalonic acidemia
more
Abdomen Gastrointestinal:
poor feeding


Clinical features from OMIM:

277380

Human phenotypes related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:

59 32 (show all 33)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 59 32 hallmark (90%) Very frequent (99-80%) HP:0001250
2 ataxia 59 32 frequent (33%) Frequent (79-30%) HP:0001251
3 muscular hypotonia 59 32 hallmark (90%) Very frequent (99-80%) HP:0001252
4 failure to thrive 59 32 hallmark (90%) Very frequent (99-80%) HP:0001508
5 developmental regression 59 32 frequent (33%) Frequent (79-30%) HP:0002376
6 feeding difficulties in infancy 59 32 hallmark (90%) Very frequent (99-80%) HP:0008872
7 psychosis 59 32 frequent (33%) Frequent (79-30%) HP:0000709
8 skin rash 59 32 hallmark (90%) Very frequent (99-80%) HP:0000988
9 lethargy 59 32 hallmark (90%) Very frequent (99-80%) HP:0001254
10 megaloblastic bone marrow 59 32 hallmark (90%) Very frequent (99-80%) HP:0001980
11 stomatitis 59 32 hallmark (90%) Very frequent (99-80%) HP:0010280
12 low-set ears 32 HP:0000369
13 high palate 32 HP:0000218
14 global developmental delay 32 HP:0001263
15 microtia 32 HP:0008551
16 pancytopenia 32 HP:0001876
17 epicanthus 32 HP:0000286
18 thrombocytopenia 32 HP:0001873
19 thin upper lip vermilion 32 HP:0000219
20 neutropenia 32 HP:0001875
21 generalized hypotonia 32 HP:0001290
22 glossitis 32 HP:0000206
23 methylmalonic aciduria 32 HP:0012120
24 incoordination 32 HP:0002311
25 megaloblastic anemia 32 HP:0001889
26 decreased methylcobalamin 32 HP:0003223
27 cystathioninuria 32 HP:0003153
28 homocystinuria 32 HP:0002156
29 hyperhomocystinemia 32 HP:0002160
30 methylmalonic acidemia 32 HP:0002912
31 cystathioninemia 32 HP:0003286
32 decreased methionine synthase activity 32 HP:0003524
33 decreased adenosylcobalamin 32 HP:0003145

UMLS symptoms related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:


lethargy, exanthema

Drugs & Therapeutics for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Search Clinical Trials , NIH Clinical Center for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Genetic Tests for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Genetic tests related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:

# Genetic test Affiliating Genes
1 Methylmalonic Aciduria and Homocystinuria, Cblf Type 29 LMBRD1

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cblf Type

MalaCards organs/tissues related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:

41
Skin, Bone, Bone Marrow

Publications for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Articles related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:

# Title Authors Year
1
Eighteen-year follow-up of a patient with cobalamin F disease (cblF): report and review. ( 21910240 )
2011

Variations for Methylmalonic Aciduria and Homocystinuria, Cblf Type

ClinVar genetic disease variations for Methylmalonic Aciduria and Homocystinuria, Cblf Type:

6 (show all 21)
# Gene Variation Type Significance SNP ID Assembly Location
1 LMBRD1 LMBRD1, 1-BP DEL, 1056G deletion Pathogenic
2 LMBRD1 LMBRD1, 2-BP DEL, 515AC deletion Pathogenic
3 LMBRD1 LMRBD1, 1-BP DEL, 404C deletion Pathogenic
4 LMBRD1 NM_018368.3(LMBRD1): c.1407T> A (p.Asp469Glu) single nucleotide variant Benign rs12648 GRCh37 Chromosome 6, 70407465: 70407465
5 LMBRD1 NM_018368.3(LMBRD1): c.1407T> A (p.Asp469Glu) single nucleotide variant Benign rs12648 GRCh38 Chromosome 6, 69697573: 69697573
6 LMBRD1 NM_018368.3(LMBRD1): c.981-3dupT duplication Conflicting interpretations of pathogenicity rs202207965 GRCh37 Chromosome 6, 70411440: 70411440
7 LMBRD1 NM_018368.3(LMBRD1): c.981-3dupT duplication Conflicting interpretations of pathogenicity rs202207965 GRCh38 Chromosome 6, 69701548: 69701548
8 LMBRD1 NM_018368.3(LMBRD1): c.801C> T (p.Arg267=) single nucleotide variant Benign/Likely benign rs34327883 GRCh37 Chromosome 6, 70423651: 70423651
9 LMBRD1 NM_018368.3(LMBRD1): c.801C> T (p.Arg267=) single nucleotide variant Benign/Likely benign rs34327883 GRCh38 Chromosome 6, 69713759: 69713759
10 LMBRD1 NM_018368.3(LMBRD1): c.1023C> T (p.Phe341=) single nucleotide variant Likely benign rs765215874 GRCh37 Chromosome 6, 70411395: 70411395
11 LMBRD1 NM_018368.3(LMBRD1): c.1023C> T (p.Phe341=) single nucleotide variant Likely benign rs765215874 GRCh38 Chromosome 6, 69701503: 69701503
12 LMBRD1 NM_018368.3(LMBRD1): c.1438A> G (p.Thr480Ala) single nucleotide variant not provided rs138023744 GRCh37 Chromosome 6, 70386413: 70386413
13 LMBRD1 NM_018368.3(LMBRD1): c.1438A> G (p.Thr480Ala) single nucleotide variant not provided rs138023744 GRCh38 Chromosome 6, 69676521: 69676521
14 LMBRD1 NM_018368.3(LMBRD1): c.540A> G (p.Leu180=) single nucleotide variant Likely benign rs138374055 GRCh37 Chromosome 6, 70451703: 70451703
15 LMBRD1 NM_018368.3(LMBRD1): c.540A> G (p.Leu180=) single nucleotide variant Likely benign rs138374055 GRCh38 Chromosome 6, 69741811: 69741811
16 LMBRD1 NM_018368.3(LMBRD1): c.291A> G (p.Val97=) single nucleotide variant Likely benign rs752864942 GRCh38 Chromosome 6, 69780510: 69780510
17 LMBRD1 NM_018368.3(LMBRD1): c.291A> G (p.Val97=) single nucleotide variant Likely benign rs752864942 GRCh37 Chromosome 6, 70490402: 70490402
18 LMBRD1 NM_018368.3(LMBRD1): c.796A> G (p.Lys266Glu) single nucleotide variant Uncertain significance rs771226867 GRCh37 Chromosome 6, 70423656: 70423656
19 LMBRD1 NM_018368.3(LMBRD1): c.796A> G (p.Lys266Glu) single nucleotide variant Uncertain significance rs771226867 GRCh38 Chromosome 6, 69713764: 69713764
20 LMBRD1 NM_018368.3(LMBRD1): c.1214C> G (p.Thr405Ser) single nucleotide variant Uncertain significance rs561265847 GRCh37 Chromosome 6, 70409059: 70409059
21 LMBRD1 NM_018368.3(LMBRD1): c.1214C> G (p.Thr405Ser) single nucleotide variant Uncertain significance rs561265847 GRCh38 Chromosome 6, 69699167: 69699167

Expression for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Search GEO for disease gene expression data for Methylmalonic Aciduria and Homocystinuria, Cblf Type.

Pathways for Methylmalonic Aciduria and Homocystinuria, Cblf Type

GO Terms for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Sources for Methylmalonic Aciduria and Homocystinuria, Cblf Type

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