[MIM 277 380, 277 400, 277 410, 614 857]

See also Cobalamin, congenital deficiency of

Rare: 1/60,000 for the most common form (cblC). Autosomal recessive transmission; Metabolic disorder due to an anomaly in the metabolism of vitamin B12.

Clinical signs:

- megaloblastic anemia 

- lethargy

- failure to thrive

- intellectual deficiency

- epilepsy

The possible genotypes and phenotypes are:

1)         combined adenosyl - and methyl-cobalamin deficiency:

-         cobalamin F: LMBRD1 gene mutation (6q13); first signs during the 1st year: developmental delay,  megaloblastic anemia or pancytopenia, stomatitis

-         cobalamin C: the most frequent (1/100,000). mutation of the MMACHC gene (1p36.3); signs (acute) in the 1St month or the 1era year: leads to methylmalonic aciduria and homocystinuria, sometimes a hemolytic uremic syndrome (see these terms); some forms tend to become clinically apparent lately (10 %): psychiatric problems, progressive encephalopathy, convulsions

-         cobalamin D: very rare; mutation of the MMADHC gene (2q23.2); results in methylmalonic aciduria or homocystinuria (see these terms)

-         cobalamin J: gene ABCD4

2)         adenosylcobalamin deficiency: cbla and cblb mutations which cause methylmalonic aciduria (see this term) close to the secondary methylmalonyl-CoA deficiency phenotype. Mutation of the MMAA (4q31.1-q31.2) or MMAB (12q24) gene. Treatment: protein restriction and intake of vitamin B12 

3)         methylcobalamin deficiency: cble and cblg mutations; extremely rare; first signs in the 1st year: megaloblastic anemia and neurological disorders (developmental delay, hypo - or hypertonia, ataxia, seizures, homocystinuria) mutation of MTRR (5p15.2-15.3) or MTR (1q43) gene. Treatment: vitamin B12 and betaine.

 Anesthetic implications: 

check complete blood count; avoid using N2O in the presence of methylmalonic aciduria (see this term)

References : 

• Felmet K, Robins B, Tilford D, Hayflick SJ. 
  Acute neurologic decompensation in an infant with cobalamin deficiency exposed to nitrous oxide. 
  J Pediatr 2000; 137: 427-8.
• Rahmandar MH, Bawcom A, Romano ME, Hamid R. 
  Cobalamin C deficiency of an adolescent with altered mental status and anorexia. 
  Pediatrics 2014; 134: e1709-17
• Krueger JM, Piantino J, Smith GM et al. 
  A treatable metabolic cause of encephalopathy: cobalamin C deficiency of a 8-year-old male.
  Pediatrics 2015; 135; e202-7.

Updated  January 2019