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GTR Home > Conditions/Phenotypes > Cobalamin C disease


Excerpted from the GeneReview: Disorders of Intracellular Cobalamin Metabolism
Disorders of intracellular cobalamin metabolism have a variable phenotype and age of onset that are influenced by the severity and location within the pathway of the defect. The prototype and best understood phenotype is cblC; it is also the most common of these disorders. The age of initial presentation of cblC spans a wide range: In utero with fetal presentation of nonimmune hydrops, cardiomyopathy, and intrauterine growth restriction. Newborns, who can have microcephaly, poor feeding, and encephalopathy. Infants, who can have poor feeding and slow growth, neurologic abnormality, and, rarely, hemolytic uremic syndrome (HUS). Toddlers, who can have poor growth, progressive microcephaly, cytopenias (including megaloblastic anemia), global developmental delay, encephalopathy, and neurologic signs such as hypotonia and seizures. Adolescents and adults, who can have neuropsychiatric symptoms, progressive cognitive decline, thromboembolic complications, and/or subacute combined degeneration of the spinal cord.

Genes See tests for all associated and related genes

  • Also known as: cblC, MMACHC
    Summary: metabolism of cobalamin associated C

  • Also known as: MSP23, NKEF-A, NKEFA, PAG, PAGA, PAGB, PRX1, PRXI, TDPX2, PRDX1
    Summary: peroxiredoxin 1

Clinical features


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Practice guidelines

  • ACMG ACT, 2022
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated C3 Acylcarnitine, Propionic Acidemia (PA) and Methylmalonic Acidemia (MMA), 2022
  • ACMG Algorithm, 2022
    American College of Medical Genetics and Genomics, Algorithm, Propionic and Methylmalonic Acidemia: C3 Elevated, 2022

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