MAHCF
MCID: MTH056
MIFTS: 35

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 72 13 70
Methylmalonic Aciduria and Homocystinuria Type Cblf 12 29 6
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cblf 20 58
Methylmalonic Aciduria Due to Vitamin B12-Release Defect 57 72
Methylmalonic Aciduria with Homocystinuria, Type Cblf 20 58
Methylmalonic Acidemia with Homocystinuria Type Cblf 20 58
Vitamin B12 Lysosomal Release Defect 57 72
Cobalamin F Disease 57 72
Mahcf 57 72
Cblf 57 72
Aciduria, Methylmalonic, and Homocystinuria, Cblf Type 39
Methylmalonic Acidemia and Homocystinuria, Cblf Type 57
Lysosomal Membrane Cobalamin Transporter Deficiency 58
Methylmalonic Acidemia and Homocystinuria Cblf Type 72
Cobalamin, Defect in Lysosomal Release of 57
Methylcobalamin Deficiency Tape F 72
Vitamin B12 Storage Disease 57
Vitamin B12 Storage Defect 72
Cobalamin F Disease; Cblf 57
Cobalamin F Deficiency 12
Cobalamin F Defect 58
Cblf Defect 58

Characteristics:

Orphanet epidemiological data:

58
methylmalonic acidemia with homocystinuria type cblf
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood;

OMIM®:

57 (Updated 05-Apr-2021)
Inheritance:
autosomal recessive

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


HPO:

31
methylmalonic aciduria and homocystinuria, cblf type:
Inheritance autosomal recessive inheritance
Onset and clinical course infantile onset


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare haematological diseases


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) (Updated 05-Apr-2021)

MalaCards based summary : Methylmalonic Aciduria and Homocystinuria, Cblf Type, also known as methylmalonic aciduria and homocystinuria 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 heart, and related phenotypes are methylmalonic aciduria and megaloblastic anemia

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) and that has material basis in homozygous or compound heterozygous mutation in the LMBRD1 gene on chromosome 6q13.

UniProtKB/Swiss-Prot : 72 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

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

58 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 methylmalonic aciduria 58 31 hallmark (90%) Very frequent (99-80%) HP:0012120
2 megaloblastic anemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0001889
3 hyperhomocystinemia 58 31 hallmark (90%) Very frequent (99-80%) HP:0002160
4 vitamin b12 deficiency 58 31 hallmark (90%) Very frequent (99-80%) HP:0100502
5 decreased adenosylcobalamin 58 31 hallmark (90%) Very frequent (99-80%) HP:0003145
6 decreased methylcobalamin 58 31 hallmark (90%) Very frequent (99-80%) HP:0003223
7 elevated circulating palmitoleylcarnitine concentration 31 hallmark (90%) HP:0031544
8 intellectual disability 58 31 frequent (33%) Frequent (79-30%) HP:0001249
9 failure to thrive 58 31 frequent (33%) Frequent (79-30%) HP:0001508
10 abnormal facial shape 58 31 frequent (33%) Frequent (79-30%) HP:0001999
11 intrauterine growth retardation 58 31 frequent (33%) Frequent (79-30%) HP:0001511
12 neurodevelopmental delay 58 31 frequent (33%) Frequent (79-30%) HP:0012758
13 lethargy 58 31 frequent (33%) Frequent (79-30%) HP:0001254
14 feeding difficulties 58 31 frequent (33%) Frequent (79-30%) HP:0011968
15 recurrent infections 58 31 frequent (33%) Frequent (79-30%) HP:0002719
16 abnormal heart morphology 58 31 frequent (33%) Frequent (79-30%) HP:0001627
17 seizure 31 frequent (33%) HP:0001250
18 hypotonia 31 frequent (33%) HP:0001252
19 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
20 skin rash 58 31 occasional (7.5%) Occasional (29-5%) HP:0000988
21 neutropenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0001875
22 reduced number of intrahepatic bile ducts 58 31 occasional (7.5%) Occasional (29-5%) HP:0006571
23 unilateral renal agenesis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000122
24 glossitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000206
25 intraventricular hemorrhage 58 31 occasional (7.5%) Occasional (29-5%) HP:0030746
26 stomatitis 58 31 occasional (7.5%) Occasional (29-5%) HP:0010280
27 seizures 58 Frequent (79-30%)
28 high palate 31 HP:0000218
29 muscular hypotonia 58 Frequent (79-30%)
30 global developmental delay 31 HP:0001263
31 microtia 31 HP:0008551
32 feeding difficulties in infancy 31 HP:0008872
33 growth delay 58 Frequent (79-30%)
34 low-set ears 31 HP:0000369
35 epicanthus 31 HP:0000286
36 thrombocytopenia 31 HP:0001873
37 thin upper lip vermilion 31 HP:0000219
38 pancytopenia 31 HP:0001876
39 generalized hypotonia 31 HP:0001290
40 methylmalonic acidemia 31 HP:0002912
41 incoordination 31 HP:0002311
42 cystathioninuria 31 HP:0003153
43 cystathioninemia 31 HP:0003286
44 hypomethioninemia 58 Excluded (0%)
45 homocystinuria 31 HP:0002156
46 elevated propionylcarnitine level 58 Very frequent (99-80%)
47 decreased methionine synthase activity 31 HP:0003524

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Growth Other:
failure to thrive

Hematology:
thrombocytopenia
neutropenia
pancytopenia
megaloblastic anemia

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

Head And Neck Eyes:
epicanthal folds

Skin Nails Hair Skin:
reticulate pigmented skin abnormalities
skin rashes

Head And Neck Ears:
low-set ears
small ears

Neurologic Central Nervous System:
lethargy
hypotonia
developmental delay
impaired coordination

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

Clinical features from OMIM®:

277380 (Updated 05-Apr-2021)

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 Type Cblf 29 LMBRD1

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cblf Type

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

40
Heart

Publications for Methylmalonic Aciduria and Homocystinuria, Cblf Type

Articles related to Methylmalonic Aciduria and Homocystinuria, Cblf Type:

(show all 13)
# Title Authors PMID Year
1
Identification of a putative lysosomal cobalamin exporter altered in the cblF defect of vitamin B12 metabolism. 6 57
19136951 2009
2
Eighteen-year follow-up of a patient with cobalamin F disease (cblF): report and review. 57 61
21910240 2011
3
A New, Atypical Case of Cobalamin F Disorder Diagnosed by Whole Exome Sequencing. 6
26997947 2016
4
Diagnostic Exome Sequencing and Tailored Bioinformatics of the Parents of a Deceased Child with Cobalamin Deficiency Suggests Digenic Inheritance of the MTR and LMBRD1 Genes. 6
24664876 2015
5
A patient with an inborn error of vitamin B12 metabolism (cblF) detected by newborn screening. 6
23776111 2013
6
Novel splice site mutations and a large deletion in three patients with the cblF inborn error of vitamin B12 metabolism. 6
21303734 2011
7
Lysosomal cobalamin accumulation in fibroblasts from a patient with an inborn error of cobalamin metabolism (cblF complementation group): visualization by electron microscope radioautography. 57
2070814 1991
8
Defective lysosomal release of vitamin B12 (cb1F): a hereditary cobalamin metabolic disorder associated with sudden death. 57
2596518 1989
9
Failure of lysosomal release of vitamin B12: a new complementation group causing methylmalonic aciduria (cblF). 57
3766542 1986
10
New disorder of vitamin B12 metabolism (cobalamin F) presenting as methylmalonic aciduria. 57
3725502 1986
11
Defect in vitamin B12 release from lysosomes: newly described inborn error of vitamin B12 metabolism. 57
4001945 1985
12
Cobalamin F disease detected by newborn screening and follow-up on a 14-year-old patient. 61
22065268 2011
13
Vitamin B12 in health and disease: part I--inherited disorders of function, absorption, and transport. 61
8775094 1995

Variations for Methylmalonic Aciduria and Homocystinuria, Cblf Type

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

6 (show top 50) (show all 66)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 LMBRD1 LMBRD1, 1-BP DEL, 1056G Deletion Pathogenic 516 GRCh37:
GRCh38:
2 LMBRD1 NM_018368.4(LMBRD1):c.404del (p.Thr135fs) Deletion Pathogenic 518 rs1562112641 GRCh37: 6:70462152-70462152
GRCh38: 6:69752260-69752260
3 LMBRD1 NM_018368.4(LMBRD1):c.1156C>T (p.Arg386Ter) SNV Pathogenic 847318 GRCh37: 6:70410689-70410689
GRCh38: 6:69700797-69700797
4 LMBRD1 NM_018368.4(LMBRD1):c.1056del (p.Asn353fs) Deletion Pathogenic 225048 rs749272546 GRCh37: 6:70411362-70411362
GRCh38: 6:69701470-69701470
5 LMBRD1 NM_018368.4(LMBRD1):c.515_516del (p.Thr172fs) Deletion Pathogenic 517 rs779151199 GRCh37: 6:70451727-70451728
GRCh38: 6:69741835-69741836
6 LMBRD1 NM_018368.4(LMBRD1):c.384T>C (p.Asp128=) SNV Conflicting interpretations of pathogenicity 357777 rs143642515 GRCh37: 6:70462172-70462172
GRCh38: 6:69752280-69752280
7 LMBRD1 NM_018368.4(LMBRD1):c.1130T>C (p.Phe377Ser) SNV Uncertain significance 449688 rs73477459 GRCh37: 6:70410715-70410715
GRCh38: 6:69700823-69700823
8 LMBRD1 NM_018368.4(LMBRD1):c.1199T>C (p.Ile400Thr) SNV Uncertain significance 851811 GRCh37: 6:70409074-70409074
GRCh38: 6:69699182-69699182
9 LMBRD1 NM_018368.4(LMBRD1):c.562C>T (p.His188Tyr) SNV Uncertain significance 863432 GRCh37: 6:70451681-70451681
GRCh38: 6:69741789-69741789
10 LMBRD1 NM_018368.4(LMBRD1):c.907C>A (p.Pro303Thr) SNV Uncertain significance 1032798 GRCh37: 6:70423545-70423545
GRCh38: 6:69713653-69713653
11 LMBRD1 NM_018368.4(LMBRD1):c.116G>A (p.Arg39Gln) SNV Uncertain significance 357778 rs886061692 GRCh37: 6:70500318-70500318
GRCh38: 6:69790426-69790426
12 LMBRD1 NM_018368.4(LMBRD1):c.88T>C (p.Trp30Arg) SNV Uncertain significance 800810 rs1582168492 GRCh37: 6:70500346-70500346
GRCh38: 6:69790454-69790454
13 LMBRD1 NM_018368.4(LMBRD1):c.73A>G (p.Ile25Val) SNV Uncertain significance 840989 GRCh37: 6:70500361-70500361
GRCh38: 6:69790469-69790469
14 LMBRD1 NM_018368.4(LMBRD1):c.400T>C (p.Cys134Arg) SNV Uncertain significance 657950 rs1582124917 GRCh37: 6:70462156-70462156
GRCh38: 6:69752264-69752264
15 LMBRD1 NM_018368.4(LMBRD1):c.1217G>A (p.Arg406Lys) SNV Uncertain significance 958218 GRCh37: 6:70409056-70409056
GRCh38: 6:69699164-69699164
16 LMBRD1 NM_018368.4(LMBRD1):c.1510G>T (p.Val504Leu) SNV Uncertain significance 684470 rs980145400 GRCh37: 6:70386163-70386163
GRCh38: 6:69676271-69676271
17 LMBRD1 NM_018368.4(LMBRD1):c.7A>G (p.Thr3Ala) SNV Uncertain significance 1009791 GRCh37: 6:70506767-70506767
GRCh38: 6:69796875-69796875
18 LMBRD1 NM_018368.4(LMBRD1):c.115C>T (p.Arg39Trp) SNV Uncertain significance 357779 rs748879055 GRCh37: 6:70500319-70500319
GRCh38: 6:69790427-69790427
19 LMBRD1 NM_018368.4(LMBRD1):c.368A>G (p.Tyr123Cys) SNV Uncertain significance 842893 GRCh37: 6:70462188-70462188
GRCh38: 6:69752296-69752296
20 LMBRD1 NM_018368.4(LMBRD1):c.830G>A (p.Arg277Gln) SNV Uncertain significance 858895 GRCh37: 6:70423622-70423622
GRCh38: 6:69713730-69713730
21 LMBRD1 NM_018368.4(LMBRD1):c.430A>G (p.Thr144Ala) SNV Uncertain significance 444690 rs12214456 GRCh37: 6:70459276-70459276
GRCh38: 6:69749384-69749384
22 LMBRD1 NM_018368.4(LMBRD1):c.*384A>C SNV Uncertain significance 908112 GRCh37: 6:70385666-70385666
GRCh38: 6:69675774-69675774
23 LMBRD1 NM_018368.4(LMBRD1):c.417G>A (p.Thr139=) SNV Uncertain significance 908178 GRCh37: 6:70459289-70459289
GRCh38: 6:69749397-69749397
24 LMBRD1 NM_018368.4(LMBRD1):c.160C>G (p.Leu54Val) SNV Uncertain significance 908179 GRCh37: 6:70500274-70500274
GRCh38: 6:69790382-69790382
25 LMBRD1 NM_018368.4(LMBRD1):c.41G>C (p.Gly14Ala) SNV Uncertain significance 908180 GRCh37: 6:70506733-70506733
GRCh38: 6:69796841-69796841
26 LMBRD1 NM_018368.4(LMBRD1):c.*220G>T SNV Uncertain significance 910059 GRCh37: 6:70385830-70385830
GRCh38: 6:69675938-69675938
27 LMBRD1 NM_018368.4(LMBRD1):c.*166A>G SNV Uncertain significance 910060 GRCh37: 6:70385884-70385884
GRCh38: 6:69675992-69675992
28 LMBRD1 NM_018368.4(LMBRD1):c.*26A>G SNV Uncertain significance 910061 GRCh37: 6:70386024-70386024
GRCh38: 6:69676132-69676132
29 LMBRD1 NM_018368.4(LMBRD1):c.1611C>G (p.Val537=) SNV Uncertain significance 910062 GRCh37: 6:70386062-70386062
GRCh38: 6:69676170-69676170
30 LMBRD1 NM_018368.4(LMBRD1):c.1501T>C (p.Phe501Leu) SNV Uncertain significance 910960 GRCh37: 6:70386350-70386350
GRCh38: 6:69676458-69676458
31 LMBRD1 NM_018368.4(LMBRD1):c.981-14G>T SNV Uncertain significance 910961 GRCh37: 6:70411451-70411451
GRCh38: 6:69701559-69701559
32 LMBRD1 NM_018368.4(LMBRD1):c.867T>A (p.Ile289=) SNV Uncertain significance 912185 GRCh37: 6:70423585-70423585
GRCh38: 6:69713693-69713693
33 LMBRD1 NM_018368.4(LMBRD1):c.582A>G (p.Ser194=) SNV Uncertain significance 912187 GRCh37: 6:70447888-70447888
GRCh38: 6:69737996-69737996
34 LMBRD1 NM_018368.4(LMBRD1):c.694T>A (p.Tyr232Asn) SNV Uncertain significance 938045 GRCh37: 6:70428916-70428916
GRCh38: 6:69719024-69719024
35 LMBRD1 NM_018368.4(LMBRD1):c.897C>T (p.Gly299=) SNV Uncertain significance 357773 rs757392138 GRCh37: 6:70423555-70423555
GRCh38: 6:69713663-69713663
36 LMBRD1 NM_018368.4(LMBRD1):c.-57T>C SNV Uncertain significance 357783 rs886061693 GRCh37: 6:70506830-70506830
GRCh38: 6:69796938-69796938
37 LMBRD1 NM_018368.4(LMBRD1):c.*77G>T SNV Uncertain significance 357767 rs886061690 GRCh37: 6:70385973-70385973
GRCh38: 6:69676081-69676081
38 LMBRD1 NM_018368.4(LMBRD1):c.-103A>G SNV Uncertain significance 357785 rs369575833 GRCh37: 6:70506876-70506876
GRCh38: 6:69796984-69796984
39 LMBRD1 NM_018368.4(LMBRD1):c.100C>G (p.Arg34Gly) SNV Uncertain significance 357780 rs773844453 GRCh37: 6:70500334-70500334
GRCh38: 6:69790442-69790442
40 LMBRD1 NM_018368.4(LMBRD1):c.802G>A (p.Ala268Thr) SNV Uncertain significance 357774 rs143758103 GRCh37: 6:70423650-70423650
GRCh38: 6:69713758-69713758
41 LMBRD1 NM_018368.4(LMBRD1):c.*125A>G SNV Uncertain significance 357766 rs886061689 GRCh37: 6:70385925-70385925
GRCh38: 6:69676033-69676033
42 LMBRD1 NM_018368.4(LMBRD1):c.1438A>G (p.Thr480Ala) SNV Uncertain significance 441041 rs138023744 GRCh37: 6:70386413-70386413
GRCh38: 6:69676521-69676521
43 LMBRD1 NM_018368.4(LMBRD1):c.796A>G (p.Lys266Glu) SNV Uncertain significance 533862 rs771226867 GRCh37: 6:70423656-70423656
GRCh38: 6:69713764-69713764
44 LMBRD1 NM_018368.4(LMBRD1):c.1214C>G (p.Thr405Ser) SNV Uncertain significance 580738 rs561265847 GRCh37: 6:70409059-70409059
GRCh38: 6:69699167-69699167
45 LMBRD1 NM_018368.4(LMBRD1):c.596C>T (p.Ser199Phe) SNV Uncertain significance 642814 rs1562105981 GRCh37: 6:70447874-70447874
GRCh38: 6:69737982-69737982
46 LMBRD1 NM_018368.4(LMBRD1):c.1347A>G (p.Ile449Met) SNV Uncertain significance 357768 rs771561971 GRCh37: 6:70407525-70407525
GRCh38: 6:69697633-69697633
47 LMBRD1 NM_018368.4(LMBRD1):c.688G>A (p.Ala230Thr) SNV Uncertain significance 658537 rs376081191 GRCh37: 6:70428922-70428922
GRCh38: 6:69719030-69719030
48 LMBRD1 NM_018368.4(LMBRD1):c.905G>A (p.Arg302His) SNV Uncertain significance 663786 rs142962811 GRCh37: 6:70423547-70423547
GRCh38: 6:69713655-69713655
49 LMBRD1 NM_018368.4(LMBRD1):c.1192T>C (p.Tyr398His) SNV Likely benign 357769 rs185334169 GRCh37: 6:70409081-70409081
GRCh38: 6:69699189-69699189
50 LMBRD1 NM_018368.4(LMBRD1):c.1206A>G (p.Arg402=) SNV Likely benign 757676 rs779802824 GRCh37: 6:70409067-70409067
GRCh38: 6:69699175-69699175

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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