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Methylmalonic aciduria and homocystinuria

MedGen UID:: 1864102
•Concept ID:: C5848324
•: Disease or Syndrome

Synonyms:	Methylmalonic acidemia and homocystinemia; Methylmalonic acidemia with homocystinuria
Modes of inheritance:	Autosomal recessive inheritance MedGen UID: 141025 •Concept ID: C0441748 • Intellectual Product Source: Orphanet A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). X-linked recessive inheritance MedGen UID: 375779 •Concept ID: C1845977 • Finding Source: Orphanet A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele. See: This record Autosomal recessive inheritance (Orphanet) X-linked recessive inheritance (Orphanet)

Related genes: Gene(s) associated with related conditions. For conditions in a hierarchy, the parent condition will list the genes associated with the children conditions.	LMBRD1, MMADHC, MMACHC, ABCD4, PRDX1

Monarch Initiative:	MONDO:0016826
OMIM® Phenotypic series:	PS277400
Orphanet:	ORPHA26

Definition

A rare inborn error of vitamin B12 (cobalamin) metabolism characterized by megaloblastic anemia, lethargy, failure to thrive, developmental delay, intellectual deficit and seizures. There are four complementation classes of cobalamin defects (cblC, cblD, cblF and cblJ) that are responsible for methylmalonic acidemia - homocystinuria (methylmalonic acidemia - homocystinuria cblC, cblD cblF and cblJ). [from ORDO]

Term Hierarchy

GTR
MeSH

CClinical test, RResearch test, OOMIM, GGeneReviews, VClinVar

Classic organic aciduria
- Methylmalonic aciduria and homocystinuria

Professional guidelines

PubMed

The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China.

Hu S, Kong X
Taiwan J Obstet Gynecol 2022 Mar;61(2):290-298. doi: 10.1016/j.tjog.2022.02.017. PMID: 35361390

Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.

Hu S, Mei S, Liu N, Kong X
BMC Med Genet 2018 Aug 29;19(1):154. doi: 10.1186/s12881-018-0666-x. PMID: 30157807 Free PMC Article

Prenatal diagnosis using genetic sequencing and identification of a novel mutation in MMACHC.

Zong Y, Liu N, Zhao Z, Kong X
BMC Med Genet 2015 Jul 7;16:48. doi: 10.1186/s12881-015-0196-8. PMID: 26149271 Free PMC Article

See all (7)

Recent clinical studies

Etiology

Epimutations in both the TESK2 and MMACHC promoters in the Epi-cblC inherited disorder of intracellular metabolism of vitamin B(12).

Oussalah A, Siblini Y, Hergalant S, Chéry C, Rouyer P, Cavicchi C, Guerrini R, Morange PE, Trégouët D, Pupavac M, Watkins D, Pastinen T, Chung WK, Ficicioglu C, Feillet F, Froese DS, Baumgartner MR, Benoist JF, Majewski J, Morrone A, Rosenblatt DS, Guéant JL
Clin Epigenetics 2022 Apr 19;14(1):52. doi: 10.1186/s13148-022-01271-1. PMID: 35440018 Free PMC Article

The Value of 1H-MRS and MRI in Combined Methylmalonic Aciduria and Homocystinuria.

Cheng A, Yao R, Cao W, Yu H
J Comput Assist Tomogr 2019 Jul/Aug;43(4):559-562. doi: 10.1097/RCT.0000000000000854. PMID: 30839328 Free PMC Article

Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity.

Beck BB, van Spronsen F, Diepstra A, Berger RM, Kömhoff M
Pediatr Nephrol 2017 May;32(5):733-741. Epub 2016 Jun 11 doi: 10.1007/s00467-016-3399-0. PMID: 27289364 Free PMC Article

Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin C type.

Gizicki R, Robert MC, Gómez-López L, Orquin J, Decarie JC, Mitchell GA, Roy MS, Ospina LH
Ophthalmology 2014 Jan;121(1):381-386. Epub 2013 Oct 11 doi: 10.1016/j.ophtha.2013.08.034. PMID: 24126030

Creatine metabolism in combined methylmalonic aciduria and homocystinuria.

Bodamer OA, Sahoo T, Beaudet AL, O'Brien WE, Bottiglieri T, Stöckler-Ipsiroglu S, Wagner C, Scaglia F
Ann Neurol 2005 Apr;57(4):557-60. doi: 10.1002/ana.20419. PMID: 15786446

See all (24)

Diagnosis

The genotype analysis and prenatal genetic diagnosis among 244 pedigrees with methylmalonic aciduria in China.

Hu S, Kong X
Taiwan J Obstet Gynecol 2022 Mar;61(2):290-298. doi: 10.1016/j.tjog.2022.02.017. PMID: 35361390

Hyperhomocysteinemia: a trigger for complement-mediated TMA?

Bernards J, Doubel P, Meeus G, Lerut E, Corveleyn A, Van Den Heuvel LP, Meersseman W, Kuypers DK, Claes KJ
Acta Clin Belg 2021 Feb;76(1):65-69. Epub 2019 Aug 11 doi: 10.1080/17843286.2019.1649039. PMID: 31401947

Molecular genetic characterization of cblC defects in 126 pedigrees and prenatal genetic diagnosis of pedigrees with combined methylmalonic aciduria and homocystinuria.

Hu S, Mei S, Liu N, Kong X
BMC Med Genet 2018 Aug 29;19(1):154. doi: 10.1186/s12881-018-0666-x. PMID: 30157807 Free PMC Article

Gene discovery in methylmalonic aciduria and homocystinuria.

Thiele J, Van Raamsdonk JM
Clin Genet 2006 May;69(5):402-3. doi: 10.1111/j.1399-0004.2006.00595c.x. PMID: 16650077

Adult-onset combined methylmalonic aciduria and homocystinuria (cblC).

Bodamer OA, Rosenblatt DS, Appel SH, Beaudet AL
Neurology 2001 Apr 24;56(8):1113. doi: 10.1212/wnl.56.8.1113. PMID: 11320193

See all (62)

Therapy

Hyperhomocysteinemia: a trigger for complement-mediated TMA?

Thrombotic microangiopathy and breastfeeding: where is the link? Questions.

Delbet JD, Ulinski T
Pediatr Nephrol 2018 Jun;33(6):985-986. Epub 2017 Aug 15 doi: 10.1007/s00467-017-3756-7. PMID: 28812099

Maculopathy and retinal degeneration in cobalamin C methylmalonic aciduria and homocystinuria.

Tsina EK, Marsden DL, Hansen RM, Fulton AB
Arch Ophthalmol 2005 Aug;123(8):1143-6. doi: 10.1001/archopht.123.8.1143. PMID: 16087854

Adult-onset combined methylmalonic aciduria and homocystinuria (cblC).

Bodamer OA, Rosenblatt DS, Appel SH, Beaudet AL
Neurology 2001 Apr 24;56(8):1113. doi: 10.1212/wnl.56.8.1113. PMID: 11320193

Cobalamin C mutation (methylmalonic aciduria and homocystinuria) in adolescence. A treatable cause of dementia and myelopathy.

Shinnar S, Singer HS
N Engl J Med 1984 Aug 16;311(7):451-4. doi: 10.1056/NEJM198408163110707. PMID: 6749192

See all (24)

Prognosis

Hyperhomocysteinemia: a trigger for complement-mediated TMA?

First Chinese case of successful pregnancy with combined methylmalonic aciduria and homocystinuria, cblC type.

Liu Y, Wang Q, Li X, Ding Y, Song J, Yang Y
Brain Dev 2015 Mar;37(3):286-91. Epub 2014 Jun 25 doi: 10.1016/j.braindev.2014.06.007. PMID: 24974159

Long-term visual outcome of methylmalonic aciduria and homocystinuria, cobalamin C type.

Gizicki R, Robert MC, Gómez-López L, Orquin J, Decarie JC, Mitchell GA, Roy MS, Ospina LH
Ophthalmology 2014 Jan;121(1):381-386. Epub 2013 Oct 11 doi: 10.1016/j.ophtha.2013.08.034. PMID: 24126030

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Lerner-Ellis JP, Tirone JC, Pawelek PD, Doré C, Atkinson JL, Watkins D, Morel CF, Fujiwara TM, Moras E, Hosack AR, Dunbar GV, Antonicka H, Forgetta V, Dobson CM, Leclerc D, Gravel RA, Shoubridge EA, Coulton JW, Lepage P, Rommens JM, Morgan K, Rosenblatt DS
Nat Genet 2006 Jan;38(1):93-100. Epub 2005 Nov 27 doi: 10.1038/ng1683. PMID: 16311595

Clinical heterogeneity and prognosis in combined methylmalonic aciduria and homocystinuria (cblC).

Rosenblatt DS, Aspler AL, Shevell MI, Pletcher BA, Fenton WA, Seashore MR
J Inherit Metab Dis 1997 Aug;20(4):528-38. doi: 10.1023/a:1005353530303. PMID: 9266389

See all (17)

Clinical prediction guides

Hyperhomocysteinemia: a trigger for complement-mediated TMA?

The Value of 1H-MRS and MRI in Combined Methylmalonic Aciduria and Homocystinuria.

Cheng A, Yao R, Cao W, Yu H
J Comput Assist Tomogr 2019 Jul/Aug;43(4):559-562. doi: 10.1097/RCT.0000000000000854. PMID: 30839328 Free PMC Article

Renal thrombotic microangiopathy in patients with cblC defect: review of an under-recognized entity.

Beck BB, van Spronsen F, Diepstra A, Berger RM, Kömhoff M
Pediatr Nephrol 2017 May;32(5):733-741. Epub 2016 Jun 11 doi: 10.1007/s00467-016-3399-0. PMID: 27289364 Free PMC Article

Identification of the gene responsible for methylmalonic aciduria and homocystinuria, cblC type.

Creatine metabolism in combined methylmalonic aciduria and homocystinuria.

Bodamer OA, Sahoo T, Beaudet AL, O'Brien WE, Bottiglieri T, Stöckler-Ipsiroglu S, Wagner C, Scaglia F
Ann Neurol 2005 Apr;57(4):557-60. doi: 10.1002/ana.20419. PMID: 15786446

See all (22)

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Methylmalonic aciduria and homocystinuria

Definition

Term Hierarchy

Professional guidelines

PubMed

Recent clinical studies

Etiology

Diagnosis

Therapy

Prognosis

Clinical prediction guides

Supplemental Content

Table of contents

Genetic Testing Registry

Clinical resources

Practice guidelines

Consumer resources

Reviews

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