Journal of Inherited Metabolic Disease

, Volume 35, Issue 1, pp 91–102

Combined methylmalonic acidemia and homocystinuria, cblC type. I. Clinical presentations, diagnosis and management

  • Nuria Carrillo-Carrasco
  • Randy J. Chandler
  • Charles P. Venditti
Review

Abstract

Combined methylmalonic acidemia and homocystinuria, cblC type, is an inborn error of intracellular cobalamin metabolism with a wide spectrum of clinical manifestations that is stated to be the most common inherited disorder of cobalamin metabolism. This metabolic disease is caused by mutations in the MMACHC gene and results in impaired intracellular synthesis of adenosylcobalamin and methylcobalamin, cofactors for the methylmalonyl-CoA mutase and methionine synthase enzymes. Elevated methylmalonic acid and homocysteine with decreased methionine production are the biochemical hallmarks of this disorder. Awareness of the diverse clinical presentations associated with cblC disease is necessary to provide a timely diagnosis, to guide management of affected individuals and to establish a framework for the future treatment of individuals detected through expanded newborn screening. This article reviews the biochemistry, clinical presentations, genotype-phenotype correlations, diagnosis and management of cblC disease.

Abbreviations

AdoCbl

5’-deoxyadenosylcobalamin

C3

Propionylcarnitine

cblC

Cobalamin C disease

CNCbl

Cyanocobalamin

IM

Intramuscular

IUGR

Intrauterine growth retardation

MeCbl

Methylcobalamin

MMA

Methylmalonic acid

MTHFR

Methylenetetrahydrofolate reductase

OHCbl

Hydroxocobalamin

SQ

Subcutaneous

tHcy

Total plasma homocysteine

Supplementary material

10545_2011_9364_MOESM1_ESM.docx (192 kb)
Supplementary Table 1Ophthalmologic complications in patients with cblC disease (DOCX 191 kb)
10545_2011_9364_MOESM2_ESM.docx (160 kb)
Supplementary Table 2Outcome of patients with cblC disease and their therapeutic regimens (DOCX 159 kb)

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Copyright information

© SSIEM and Springer (outside the USA) 2011

Authors and Affiliations

  • Nuria Carrillo-Carrasco
    • 1
  • Randy J. Chandler
    • 1
    • 2
  • Charles P. Venditti
    • 1
  1. 1.Organic Acid Research Section, Genetics and Molecular Biology BranchNational Human Genome Research Institute, National Institutes of HealthBethesdaUSA
  2. 2.Institute for Biomedical SciencesThe George Washington UniversityWashington, DCUSA

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