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

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  • Published:
Journal of Inherited Metabolic Disease

Abstract

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.

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Abbreviations

cblC:

Cobalamin C disease

CBS:

Cystathionine beta synthase

CNCbl:

Cyanocobalamin

IM:

Intramuscular

MeCbl:

Methylcobalamin

MMA:

Methylmalonic acid

MTHFR:

Methylenetetrahydrofolate reductase

OHCbl:

Hydroxocobalamin

SAM:

S-Adenosylmethionine

SCD:

Subacute combined degeneration of the spinal cord

tHcy:

Total plasma homocysteine

HcyTL:

Homocysteine thiolactone

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Authors and Affiliations

  1. Organic Acid Research Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health, Building 49, Room 4A18, Bethesda, MD, 20892, USA

    Nuria Carrillo-Carrasco & Charles P. Venditti

Authors
  1. Nuria Carrillo-Carrasco
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  2. Charles P. Venditti
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Corresponding author

Correspondence to Charles P. Venditti.

Additional information

Communicated by: Johan Lodewijk Karel Van Hove

References to electronic databases: Methylmalonic aciduria and homocystinuria cblC type: OMIM #277400.

MMACHC gene: OMIM *609831.

Methionine synthase: EC 1.16.1.8.

Methylmalonyl-CoA mutase: EC 5.4.99.2.

Competing interests: None declared

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Table 1

Ophthalmologic complications in patients with cblC disease (DOCX 191 kb)

Supplementary Table 2

Outcome of patients with cblC disease and their therapeutic regimens (DOCX 159 kb)

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Carrillo-Carrasco, N., Venditti, C.P. Combined methylmalonic acidemia and homocystinuria, cblC type. II. Complications, pathophysiology, and outcomes. J Inherit Metab Dis 35, 103–114 (2012). https://doi.org/10.1007/s10545-011-9365-x

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  • DOI: https://doi.org/10.1007/s10545-011-9365-x

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