Ye et al (AJHG (2013) 93, 506-514) described a new X-linked disorder of cobalamin processing caused by transcriptional dysregulation of MMACHC (cblC, combined methylmalonic acidema and homocysteinemia). This disorder is named cblX and is caused by mutations in HCFC1. HCFC1 is a global transcriptional regulator and in addition to the biochemical phenotype, these patients also have significant neurologic consequences including severe epilepsy and intellectual disability. The authors make the point that this disorder is an example of a unique disease mechanism where global transcriptional abnormalities can lead to complex genetic disorders with a significant biochemical component.
Hilary Vernon MD PhD