MAHCJ
MCID: MTH051
MIFTS: 28

Methylmalonic Aciduria and Homocystinuria, Cblj Type (MAHCJ)

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

Aliases & Classifications for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

Name: Methylmalonic Aciduria and Homocystinuria, Cblj Type 57 20 13 70
Methylmalonic Acidemia with Homocystinuria, Type Cblj 20 58 29 6
Mahcj 57 20 72
Combined Defect in Adenosylcobalamin and Methylcobalamin Synthesis, Type Cblj 20 58
Methylmalonic Aciduria with Homocystinuria, Type Cblj 20 58
Cobalamin J Defect 20 58
Cblj Defects 20 58
Aciduria, Methylmalonic, and Homocystinuria, Cblj Type 39
Methylmalonic Acidemia with Homocystinuria Type Cblj 20
Methylmalonic Aciduria and Homocystinuria Type Cblj 72

Characteristics:

Orphanet epidemiological data:

58
methylmalonic acidemia with homocystinuria, type cblj
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

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

Miscellaneous:
onset at birth
two unrelated patients have been reported (last curated october 2012)


HPO:

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


Classifications:

Orphanet: 58  
Inborn errors of metabolism
Rare haematological diseases


Summaries for Methylmalonic Aciduria and Homocystinuria, Cblj Type

OMIM® : 57 Combined methylmalonic aciduria (MMA) and homocystinuria is a genetically heterogeneous metabolic disorder of cobalamin (cbl; vitamin B12) metabolism, which is essential for hematologic and neurologic function. Biochemically, 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). The cblJ type is phenotypically and biochemically similar to the cblF type (MAHCF; 277380) (summary by Coelho et al., 2012). (614857) (Updated 05-Apr-2021)

MalaCards based summary : Methylmalonic Aciduria and Homocystinuria, Cblj Type, also known as methylmalonic acidemia with homocystinuria, type cblj, is related to methylmalonic aciduria and homocystinuria, cblf type and methylmalonic aciduria and homocystinuria, cbld type, and has symptoms including lethargy An important gene associated with Methylmalonic Aciduria and Homocystinuria, Cblj Type is ABCD4 (ATP Binding Cassette Subfamily D Member 4). Related phenotypes are global developmental delay and hypertelorism

UniProtKB/Swiss-Prot : 72 Methylmalonic aciduria and homocystinuria type cblJ: A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay.

Related Diseases for Methylmalonic Aciduria and Homocystinuria, Cblj Type

Diseases related to Methylmalonic Aciduria and Homocystinuria, Cblj Type via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 methylmalonic aciduria and homocystinuria, cblf type 10.9
2 methylmalonic aciduria and homocystinuria, cbld type 10.9

Symptoms & Phenotypes for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

31 (show all 27)
# Description HPO Frequency HPO Source Accession
1 global developmental delay 31 occasional (7.5%) HP:0001263
2 hypertelorism 31 occasional (7.5%) HP:0000316
3 gastroesophageal reflux 31 occasional (7.5%) HP:0002020
4 cryptorchidism 31 occasional (7.5%) HP:0000028
5 wide intermamillary distance 31 occasional (7.5%) HP:0006610
6 micrognathia 31 occasional (7.5%) HP:0000347
7 atrial septal defect 31 occasional (7.5%) HP:0001631
8 coarctation of aorta 31 occasional (7.5%) HP:0001680
9 pulmonary arterial hypertension 31 occasional (7.5%) HP:0002092
10 cerebral atrophy 31 occasional (7.5%) HP:0002059
11 decreased methylcobalamin 31 occasional (7.5%) HP:0003223
12 decreased methionine synthase activity 31 occasional (7.5%) HP:0003524
13 inguinal hernia 31 HP:0000023
14 anemia 31 HP:0001903
15 growth delay 31 HP:0001510
16 thrombocytopenia 31 HP:0001873
17 neutropenia 31 HP:0001875
18 lethargy 31 HP:0001254
19 feeding difficulties 31 HP:0011968
20 tachypnea 31 HP:0002789
21 methylmalonic aciduria 31 HP:0012120
22 generalized hypotonia 31 HP:0001290
23 methylmalonic acidemia 31 HP:0002912
24 abnormal posturing 31 HP:0002533
25 hyperhomocystinemia 31 HP:0002160
26 homocystinuria 31 HP:0002156
27 decreased adenosylcobalamin 31 HP:0003145

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Abdomen External Features:
inguinal hernia

Neurologic Central Nervous System:
lethargy
abnormal posturing
delayed psychomotor development (1 patient)
cerebral atrophy (1 patient)

Laboratory Abnormalities:
methylmalonic aciduria
methylmalonic acidemia
homocystinuria
homocystinemia
decreased adenosylcobalamin (adocbl)
more
Abdomen Gastrointestinal:
poor feeding
gastroesophageal reflux (1 patient)

Genitourinary Internal Genitalia Male:
cryptorchidism (1 patient)

Head And Neck Eyes:
hypertelorism (1 patient)

Cardiovascular Vascular:
pulmonary hypertension (1 patient)

Hematology:
anemia
thrombocytopenia
neutropenia

Respiratory:
tachypnea
breathing difficulties in the neonatal period

Muscle Soft Tissue:
hypotonia

Growth Other:
poor growth

Cardiovascular Heart:
atrial septal defect (1 patient)
coarctation of the aorta (1 patient)
enlarged right ventricle (1 patient)
small left ventricle (1 patient)

Head And Neck Face:
micrognathia (1 patient)

Chest Breasts:
widely spaced nipples (1 patient)

Clinical features from OMIM®:

614857 (Updated 05-Apr-2021)

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


lethargy

Drugs & Therapeutics for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

Genetic Tests for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

# Genetic test Affiliating Genes
1 Methylmalonic Acidemia with Homocystinuria, Type Cblj 29 ABCD4

Anatomical Context for Methylmalonic Aciduria and Homocystinuria, Cblj Type

Publications for Methylmalonic Aciduria and Homocystinuria, Cblj Type

Articles related to Methylmalonic Aciduria and Homocystinuria, Cblj Type:

# Title Authors PMID Year
1
Mutations in ABCD4 cause a new inborn error of vitamin B12 metabolism. 6 57
22922874 2012
2
Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry. 61
30773687 2019

Variations for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

6 (show top 50) (show all 66)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 ABCD4 NM_005050.4(ABCD4):c.1588C>T (p.Gln530Ter) SNV Pathogenic 583152 rs767795583 GRCh37: 14:74754561-74754561
GRCh38: 14:74287858-74287858
2 ABCD4 ABCD4, 1456G-T SNV Pathogenic 37322 GRCh37:
GRCh38:
3 ABCD4 NM_005050.4(ABCD4):c.542+1G>T SNV Pathogenic 280107 rs769364566 GRCh37: 14:74763035-74763035
GRCh38: 14:74296332-74296332
4 ABCD4 NM_005050.4(ABCD4):c.1746_1747insCT (p.Glu583fs) Insertion Pathogenic 37320 rs387907315 GRCh37: 14:74753409-74753410
GRCh38: 14:74286706-74286707
5 ABCD4 NM_005050.4(ABCD4):c.719+2T>G SNV Likely pathogenic 976682 GRCh37: 14:74761849-74761849
GRCh38: 14:74295146-74295146
6 ABCD4 NM_005050.4(ABCD4):c.556G>A (p.Gly186Arg) SNV Likely pathogenic 976683 GRCh37: 14:74762669-74762669
GRCh38: 14:74295966-74295966
7 ABCD4 NM_005050.4(ABCD4):c.1411C>T (p.Arg471Trp) SNV Conflicting interpretations of pathogenicity 381876 rs45568335 GRCh37: 14:74756738-74756738
GRCh38: 14:74290035-74290035
8 ABCD4 NM_005050.4(ABCD4):c.1337A>G (p.Gln446Arg) SNV Uncertain significance 999745 GRCh37: 14:74756812-74756812
GRCh38: 14:74290109-74290109
9 ABCD4 NM_005050.4(ABCD4):c.1325G>A (p.Arg442Gln) SNV Uncertain significance 1008655 GRCh37: 14:74756996-74756996
GRCh38: 14:74290293-74290293
10 ABCD4 NM_005050.4(ABCD4):c.1136C>T (p.Ala379Val) SNV Uncertain significance 1008673 GRCh37: 14:74757185-74757185
GRCh38: 14:74290482-74290482
11 ABCD4 NM_005050.4(ABCD4):c.1049C>T (p.Thr350Met) SNV Uncertain significance 852074 GRCh37: 14:74759059-74759059
GRCh38: 14:74292356-74292356
12 ABCD4 NM_005050.4(ABCD4):c.1426T>C (p.Tyr476His) SNV Uncertain significance 860816 GRCh37: 14:74756216-74756216
GRCh38: 14:74289513-74289513
13 ABCD4 NM_005050.4(ABCD4):c.1559+7_1559+11del Deletion Uncertain significance 936016 GRCh37: 14:74754899-74754903
GRCh38: 14:74288196-74288200
14 ABCD4 NM_005050.4(ABCD4):c.611T>C (p.Leu204Ser) SNV Uncertain significance 940798 GRCh37: 14:74762614-74762614
GRCh38: 14:74295911-74295911
15 ABCD4 NM_005050.4(ABCD4):c.1028+5G>A SNV Uncertain significance 950209 GRCh37: 14:74759249-74759249
GRCh38: 14:74292546-74292546
16 ABCD4 NM_005050.4(ABCD4):c.801G>C (p.Glu267Asp) SNV Uncertain significance 957845 GRCh37: 14:74759870-74759870
GRCh38: 14:74293167-74293167
17 ABCD4 NM_005050.4(ABCD4):c.1402G>A (p.Gly468Arg) SNV Uncertain significance 1026083 GRCh37: 14:74756747-74756747
GRCh38: 14:74290044-74290044
18 ABCD4 NM_005050.4(ABCD4):c.956A>G (p.Tyr319Cys) SNV Uncertain significance 37319 rs201777056 GRCh37: 14:74759326-74759326
GRCh38: 14:74292623-74292623
19 ABCD4 NM_005050.4(ABCD4):c.752G>A (p.Arg251His) SNV Uncertain significance 386273 rs139315421 GRCh37: 14:74759919-74759919
GRCh38: 14:74293216-74293216
20 ABCD4 NM_005050.4(ABCD4):c.1633G>A (p.Ala545Thr) SNV Uncertain significance 934796 GRCh37: 14:74754516-74754516
GRCh38: 14:74287813-74287813
21 ABCD4 NM_005050.4(ABCD4):c.821T>A (p.Ile274Asn) SNV Uncertain significance 952022 GRCh37: 14:74759566-74759566
GRCh38: 14:74292863-74292863
22 ABCD4 NM_005050.4(ABCD4):c.1691G>A (p.Arg564His) SNV Uncertain significance 956299 GRCh37: 14:74753465-74753465
GRCh38: 14:74286762-74286762
23 ABCD4 NM_005050.4(ABCD4):c.89T>G (p.Val30Gly) SNV Uncertain significance 957846 GRCh37: 14:74766921-74766921
GRCh38: 14:74300218-74300218
24 ABCD4 NM_005050.4(ABCD4):c.1095C>T (p.Gly365=) SNV Uncertain significance 1038880 GRCh37: 14:74759013-74759013
GRCh38: 14:74292310-74292310
25 ABCD4 NM_005050.4(ABCD4):c.1255A>G (p.Ile419Val) SNV Uncertain significance 1039802 GRCh37: 14:74757066-74757066
GRCh38: 14:74290363-74290363
26 ABCD4 NM_005050.4(ABCD4):c.463C>T (p.Arg155Trp) SNV Uncertain significance 1045799 GRCh37: 14:74763115-74763115
GRCh38: 14:74296412-74296412
27 ABCD4 NM_005050.4(ABCD4):c.727C>T (p.His243Tyr) SNV Uncertain significance 941066 GRCh37: 14:74759944-74759944
GRCh38: 14:74293241-74293241
28 ABCD4 NM_005050.4(ABCD4):c.1306G>A (p.Gly436Ser) SNV Uncertain significance 965796 GRCh37: 14:74757015-74757015
GRCh38: 14:74290312-74290312
29 ABCD4 NM_005050.4(ABCD4):c.859G>A (p.Val287Ile) SNV Uncertain significance 966702 GRCh37: 14:74759528-74759528
GRCh38: 14:74292825-74292825
30 ABCD4 NM_005050.4(ABCD4):c.1019A>G (p.Tyr340Cys) SNV Uncertain significance 971876 GRCh37: 14:74759263-74759263
GRCh38: 14:74292560-74292560
31 ABCD4 NM_005050.4(ABCD4):c.1794G>C (p.Trp598Cys) SNV Uncertain significance 973444 GRCh37: 14:74753191-74753191
GRCh38: 14:74286488-74286488
32 ABCD4 NM_005050.4(ABCD4):c.40C>G (p.Pro14Ala) SNV Uncertain significance 849796 GRCh37: 14:74766970-74766970
GRCh38: 14:74300267-74300267
33 ABCD4 NM_005050.4(ABCD4):c.364C>T (p.Leu122Phe) SNV Uncertain significance 568694 rs141808601 GRCh37: 14:74764694-74764694
GRCh38: 14:74297991-74297991
34 ABCD4 NM_005050.4(ABCD4):c.352C>T (p.His118Tyr) SNV Uncertain significance 569782 rs371774856 GRCh37: 14:74764706-74764706
GRCh38: 14:74298003-74298003
35 ABCD4 NM_005050.4(ABCD4):c.406C>T (p.Arg136Trp) SNV Uncertain significance 574740 rs145141432 GRCh37: 14:74764652-74764652
GRCh38: 14:74297949-74297949
36 ABCD4 NM_005050.4(ABCD4):c.1752+2T>C SNV Uncertain significance 575290 rs151116417 GRCh37: 14:74753402-74753402
GRCh38: 14:74286699-74286699
37 ABCD4 NM_005050.4(ABCD4):c.1346C>T (p.Thr449Met) SNV Uncertain significance 587476 rs969369250 GRCh37: 14:74756803-74756803
GRCh38: 14:74290100-74290100
38 ABCD4 NM_005050.4(ABCD4):c.565A>G (p.Ser189Gly) SNV Uncertain significance 646672 rs183607306 GRCh37: 14:74762660-74762660
GRCh38: 14:74295957-74295957
39 ABCD4 NM_005050.4(ABCD4):c.503C>T (p.Pro168Leu) SNV Uncertain significance 648720 rs747354548 GRCh37: 14:74763075-74763075
GRCh38: 14:74296372-74296372
40 ABCD4 NM_005050.4(ABCD4):c.1578G>A (p.Pro526=) SNV Uncertain significance 652295 rs555792734 GRCh37: 14:74754571-74754571
GRCh38: 14:74287868-74287868
41 ABCD4 NM_005050.4(ABCD4):c.1680C>G (p.Ser560Arg) SNV Uncertain significance 657074 rs138753274 GRCh37: 14:74753476-74753476
GRCh38: 14:74286773-74286773
42 ABCD4 NM_005050.4(ABCD4):c.1352T>C (p.Phe451Ser) SNV Uncertain significance 660320 rs1594861158 GRCh37: 14:74756797-74756797
GRCh38: 14:74290094-74290094
43 ABCD4 NM_005050.4(ABCD4):c.1465G>A (p.Asp489Asn) SNV Uncertain significance 424218 rs139901585 GRCh37: 14:74755460-74755460
GRCh38: 14:74288757-74288757
44 ABCD4 NM_005050.4(ABCD4):c.555C>T (p.Leu185=) SNV Likely benign 508257 rs188108983 GRCh37: 14:74762670-74762670
GRCh38: 14:74295967-74295967
45 ABCD4 NM_005050.4(ABCD4):c.1118+9C>T SNV Likely benign 512105 rs370581068 GRCh37: 14:74758981-74758981
GRCh38: 14:74292278-74292278
46 ABCD4 NM_005050.4(ABCD4):c.141G>C (p.Leu47Phe) SNV Likely benign 372930 rs147446660 GRCh37: 14:74766869-74766869
GRCh38: 14:74300166-74300166
47 ABCD4 NM_005050.4(ABCD4):c.751C>T (p.Arg251Cys) SNV Likely benign 382479 rs141868117 GRCh37: 14:74759920-74759920
GRCh38: 14:74293217-74293217
48 ABCD4 NM_005050.4(ABCD4):c.1056G>A (p.Leu352=) SNV Likely benign 668490 rs542032495 GRCh37: 14:74759052-74759052
GRCh38: 14:74292349-74292349
49 ABCD4 NM_005050.4(ABCD4):c.1083C>T (p.Cys361=) SNV Likely benign 681957 rs377583331 GRCh37: 14:74759025-74759025
GRCh38: 14:74292322-74292322
50 ABCD4 NM_005050.4(ABCD4):c.1752+7G>A SNV Likely benign 721931 rs376322555 GRCh37: 14:74753397-74753397
GRCh38: 14:74286694-74286694

UniProtKB/Swiss-Prot genetic disease variations for Methylmalonic Aciduria and Homocystinuria, Cblj Type:

72
# Symbol AA change Variation ID SNP ID
1 ABCD4 p.Tyr319Cys VAR_069097 rs201777056

Expression for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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

Pathways for Methylmalonic Aciduria and Homocystinuria, Cblj Type

GO Terms for Methylmalonic Aciduria and Homocystinuria, Cblj Type

Sources for Methylmalonic Aciduria and Homocystinuria, Cblj Type

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11 DGIdb
17 EFO
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45 MESH via Orphanet
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56 OMIM via Orphanet
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71 UMLS via Orphanet
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