U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Homocystinuria without methylmalonic aciduria

MedGen UID:
929148
•Concept ID:
C4303479
•
Disease or Syndrome
Synonyms: Functional methionine synthase deficiency; functional methionine synthase deficiency; homocystinuria without methylmalonic aciduria; Methylcobalamin deficiency; methylcobalamin deficiency
SNOMED CT: Homocystinuria without methylmalonic aciduria (721225009); Functional methionine synthase deficiency (721225009)
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).
Autosomal recessive inheritance (Orphanet)
 
Monarch Initiative: MONDO:0018964
Orphanet: ORPHA622

Definition

An inborn error of vitamin B12 (cobalamin) metabolism characterised by megaloblastic anaemia, encephalopathy and sometimes, developmental delay, and associated with homocystinuria and hyperhomocysteinemia. There are three types of homocystinuria without methylmalonic aciduria; cblE, cblG and cblD-variant 1 (cblDv1). These disorders are caused by a functional deficiency of the cytoplasmic enzyme methionine synthase (MS), which catalyses remethylation of homocysteine to form methionine. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • Homocystinuria without methylmalonic aciduria

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: 30157807Free PMC Article
Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management.
Carrillo-Carrasco N, Chandler RJ, Venditti CP
J Inherit Metab Dis 2012 Jan;35(1):91-102. Epub 2011 Jul 12 doi: 10.1007/s10545-011-9364-y. PMID: 21748409Free PMC Article

Recent clinical studies

Etiology

Clinical and Molecular Spectrum of Patients with Methylmalonic Acidemia.
Gupta N, Endrakanti M, Bhat M, Rao N, Kaur R, Kabra M
Indian J Pediatr 2024 Jul;91(7):675-681. Epub 2023 Jul 8 doi: 10.1007/s12098-023-04651-4. PMID: 37420116
Late-onset cblC defect: clinical, biochemical and molecular analysis.
Ding S, Ling S, Liang L, Qiu W, Zhang H, Chen T, Zhan X, Xu F, Gu X, Han L
Orphanet J Rare Dis 2023 Sep 28;18(1):306. doi: 10.1186/s13023-023-02890-4. PMID: 37770946Free PMC Article
Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria.
Schnabel E, Kölker S, Gleich F, Feyh P, Hörster F, Haas D, Fang-Hoffmann J, Morath M, Gramer G, Röschinger W, Garbade SF, Hoffmann GF, Okun JG, Mütze U
Nutrients 2023 Jul 28;15(15) doi: 10.3390/nu15153355. PMID: 37571294Free PMC Article
Inherited metabolic diseases mimicking hereditary spastic paraplegia (HSP): a chance for treatment.
Teive HAG, Camargo CHF, Pereira ER, Coutinho L, Munhoz RP
Neurogenetics 2022 Jul;23(3):167-177. Epub 2022 Apr 9 doi: 10.1007/s10048-022-00688-3. PMID: 35397036
Intracellular processing of vitamin B(12) by MMACHC (CblC).
Hannibal L, Jacobsen DW
Vitam Horm 2022;119:275-298. Epub 2022 Mar 15 doi: 10.1016/bs.vh.2022.02.001. PMID: 35337623

Diagnosis

Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias.
Reischl-Hajiabadi AT, Schnabel E, Gleich F, Mengler K, Lindner M, Burgard P, Posset R, Lommer-Steinhoff S, Grünert SC, Thimm E, Freisinger P, Hennermann JB, Krämer J, Gramer G, Lenz D, Christ S, Hörster F, Hoffmann GF, Garbade SF, Kölker S, Mütze U
J Inherit Metab Dis 2024 Jul;47(4):674-689. Epub 2024 Apr 2 doi: 10.1002/jimd.12731. PMID: 38563533
Late-onset cblC defect: clinical, biochemical and molecular analysis.
Ding S, Ling S, Liang L, Qiu W, Zhang H, Chen T, Zhan X, Xu F, Gu X, Han L
Orphanet J Rare Dis 2023 Sep 28;18(1):306. doi: 10.1186/s13023-023-02890-4. PMID: 37770946Free PMC Article
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: 30157807Free PMC Article
Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management.
Carrillo-Carrasco N, Chandler RJ, Venditti CP
J Inherit Metab Dis 2012 Jan;35(1):91-102. Epub 2011 Jul 12 doi: 10.1007/s10545-011-9364-y. PMID: 21748409Free PMC Article

Therapy

Adult-onset CblC deficiency: a challenging diagnosis involving different adult clinical specialists.
Kalantari S, Brezzi B, Bracciamà V, Barreca A, Nozza P, Vaisitti T, Amoroso A, Deaglio S, Manganaro M, Porta F, Spada M
Orphanet J Rare Dis 2022 Feb 2;17(1):33. doi: 10.1186/s13023-022-02179-y. PMID: 35109910Free PMC Article
Prevalence of methylmalonic acidemia among newborns and the clinical-suspected population: a meta-analyse.
Jin L, Han X, He F, Zhang C
J Matern Fetal Neonatal Med 2022 Dec;35(25):8952-8967. Epub 2021 Nov 30 doi: 10.1080/14767058.2021.2008351. PMID: 34847798
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
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: 27289364Free PMC Article
Methylmalonic aciduria with homocystinuria.
Ribes A, Vilaseca MA, Briones P, Maya A, Sabater J, Pascual P, Alvarez L, Ros J, Gonzalez Pascual E
J Inherit Metab Dis 1984;7 Suppl 2:129-30. doi: 10.1007/978-94-009-5612-4_39. PMID: 6434865

Prognosis

Late-onset cblC defect: clinical, biochemical and molecular analysis.
Ding S, Ling S, Liang L, Qiu W, Zhang H, Chen T, Zhan X, Xu F, Gu X, Han L
Orphanet J Rare Dis 2023 Sep 28;18(1):306. doi: 10.1186/s13023-023-02890-4. PMID: 37770946Free PMC Article
Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria.
Schnabel E, Kölker S, Gleich F, Feyh P, Hörster F, Haas D, Fang-Hoffmann J, Morath M, Gramer G, Röschinger W, Garbade SF, Hoffmann GF, Okun JG, Mütze U
Nutrients 2023 Jul 28;15(15) doi: 10.3390/nu15153355. PMID: 37571294Free PMC Article
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
Analysis of 70 patients with hydrocephalus due to cobalamin C deficiency.
He R, Zhang H, Kang L, Li H, Shen M, Zhang Y, Mo R, Liu Y, Song J, Chen Z, Liu Y, Jin Y, Li M, Dong H, Zheng H, Li D, Qin J, Zhang H, Huang M, Liang D, Tian Y, Yao H, Yang Y
Neurology 2020 Dec 8;95(23):e3129-e3137. Epub 2020 Sep 17 doi: 10.1212/WNL.0000000000010912. PMID: 32943488
Management of hemolytic uremic syndrome.
Loirat C, Saland J, Bitzan M
Presse Med 2012 Mar;41(3 Pt 2):e115-35. Epub 2012 Jan 27 doi: 10.1016/j.lpm.2011.11.013. PMID: 22284541

Clinical prediction guides

Outcomes after newborn screening for propionic and methylmalonic acidemia and homocystinurias.
Reischl-Hajiabadi AT, Schnabel E, Gleich F, Mengler K, Lindner M, Burgard P, Posset R, Lommer-Steinhoff S, Grünert SC, Thimm E, Freisinger P, Hennermann JB, Krämer J, Gramer G, Lenz D, Christ S, Hörster F, Hoffmann GF, Garbade SF, Kölker S, Mütze U
J Inherit Metab Dis 2024 Jul;47(4):674-689. Epub 2024 Apr 2 doi: 10.1002/jimd.12731. PMID: 38563533
Clinical and Molecular Spectrum of Patients with Methylmalonic Acidemia.
Gupta N, Endrakanti M, Bhat M, Rao N, Kaur R, Kabra M
Indian J Pediatr 2024 Jul;91(7):675-681. Epub 2023 Jul 8 doi: 10.1007/s12098-023-04651-4. PMID: 37420116
Late-onset cblC defect: clinical, biochemical and molecular analysis.
Ding S, Ling S, Liang L, Qiu W, Zhang H, Chen T, Zhan X, Xu F, Gu X, Han L
Orphanet J Rare Dis 2023 Sep 28;18(1):306. doi: 10.1186/s13023-023-02890-4. PMID: 37770946Free PMC Article
Combined Newborn Screening Allows Comprehensive Identification also of Attenuated Phenotypes for Methylmalonic Acidurias and Homocystinuria.
Schnabel E, Kölker S, Gleich F, Feyh P, Hörster F, Haas D, Fang-Hoffmann J, Morath M, Gramer G, Röschinger W, Garbade SF, Hoffmann GF, Okun JG, Mütze U
Nutrients 2023 Jul 28;15(15) doi: 10.3390/nu15153355. PMID: 37571294Free PMC Article
Mutations in Hcfc1 and Ronin result in an inborn error of cobalamin metabolism and ribosomopathy.
Chern T, Achilleos A, Tong X, Hill MC, Saltzman AB, Reineke LC, Chaudhury A, Dasgupta SK, Redhead Y, Watkins D, Neilson JR, Thiagarajan P, Green JBA, Malovannaya A, Martin JF, Rosenblatt DS, Poché RA
Nat Commun 2022 Jan 10;13(1):134. doi: 10.1038/s41467-021-27759-7. PMID: 35013307Free PMC Article

Recent systematic reviews

Late-onset methylmalonic acidemia and homocysteinemia (cblC disease): systematic review.
Arhip L, Brox-Torrecilla N, Romero I, Motilla M, Serrano-Moreno C, Miguélez M, Cuerda C
Orphanet J Rare Dis 2024 Jan 20;19(1):20. doi: 10.1186/s13023-024-03021-3. PMID: 38245797Free PMC Article

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Reviews

    Related information

    • ClinVar
      Related medical variations
    • PMC Articles
      Related information in PubMed Central Links
    • PubMed
      Related literature resources in PubMed

    Recent activity

    Clear Turn Off Turn On

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...