Inherited Intracellular Cobalamin Metabolism Defects: Mode of Inheritance
Yes, inherited intracellular cobalamin metabolism defects are autosomal recessive disorders. 1, 2
Inheritance Pattern
- All inborn errors of intracellular cobalamin metabolism (designated cblA through cblG) are inherited as autosomal recessive traits. 1, 2
- These single gene defects require inheritance of pathogenic variants from both parents for disease manifestation. 1
- The disorders affect the intracellular processing and conversion of dietary vitamin B12 into its two metabolically active forms: adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). 3
Specific Cobalamin Metabolism Defects
The intracellular cobalamin defects include multiple complementation groups, all following autosomal recessive inheritance:
- cblA and cblB: Cause isolated methylmalonic acidemia 2
- cblC: The most common inborn cobalamin metabolism error, causing combined methylmalonic acidemia and hyperhomocysteinemia 3, 2
- cblD variants: Can cause isolated methylmalonic acidemia (variant 2), isolated hyperhomocysteinemia (variant 1), or combined abnormalities (classic cblD) 2
- cblE and cblG: Cause isolated hyperhomocysteinemia 2
- cblF: Causes combined methylmalonic acidemia and hyperhomocysteinemia 2
Clinical Context
- Most organic acidemias and other inborn errors of metabolism identified through organic acid analysis are inherited as autosomal recessive traits. 4
- Metabolic disorders associated with autism spectrum disorders are also typically autosomal recessive in nature. 4
- The identification of an affected individual has important implications for other family members, who may also require metabolic testing and genetic counseling. 4