Journal of Inherited Metabolic Disease

, Volume 35, Issue 1, pp 103–114 | Cite as

Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes

  • Nuria Carrillo-Carrasco
  • Charles P. Venditti


Combined methylmalonic acidemia and homocystinuria, cblC type, is stated to be the most common inborn error of intracellular cobalamin metabolism. The disorder can display a wide spectrum of clinical manifestations, spanning the prenatal period through late adulthood. While increased homocysteine concentrations and impaired methyl group metabolism may contribute to disease-related complications, the characteristic macular and retinal degeneration seen in many affected patients appears to be unique to cblC disease. The early detection of cblC disease by newborn screening mandates a careful assessment of therapeutic approaches and provides a new opportunity to improve the outcome of affected patients. The following article reviews the current knowledge on the complications, pathophysiology, and outcome of cblC disease in an effort to better guide clinical practice and future therapeutic trials.


Betaine Newborn Screening Cobalamin Thrombotic Microangiopathy Homocystinuria 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Cobalamin C disease


Cystathionine beta synthase








Methylmalonic acid


Methylenetetrahydrofolate reductase






Subacute combined degeneration of the spinal cord


Total plasma homocysteine


Homocysteine thiolactone

Supplementary material

10545_2011_9365_MOESM1_ESM.docx (192 kb)
Supplementary Table 1 Ophthalmologic complications in patients with cblC disease (DOCX 191 kb)
10545_2011_9365_MOESM2_ESM.docx (160 kb)
Supplementary Table 2 Outcome 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

  1. 1.Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research InstituteNational Institutes of HealthBethesdaUSA

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