Symptoms of cobalamin activation disorders in relation to ethnicity and Native American tribal affiliation: An exploratory study

The Cobalamin activation disorders (CblA‐CblG) are deleterious inborn errors of Vitamin B 12 activation, resulting in severe intellectual disability, vision impairment, and seizures. Although cobalamin activation disorders are exceedingly rare, typically occurring 1 in every 200,000 births, Phoenix Children's Hospital has an unusually high number of patients (n=21). We conducted a retrospective, exploratory examination of medical records to identify symptom trends in individuals clinically diagnosed with CblC (n=16) in relation to race, ethnicity, and tribal affiliation. This study is unique due to our direct access to a large population of children with this condition, the majority of whom are Native American (n=6) or Hispanic (n=8), while the remaining 2 are of Caucasian descent. We also examined the symptoms of two Native American children believed to have a novel mutation related to cobalamin metabolism. Of the 16 individuals clinically diagnosed with CblC, those with the most severe eye abnormalities tended to be of Athabascan descent. In addition, growth delays were present in 5 children, with no apparent connection to race or ethnicity. Finally, two children believed to exhibit a novel mutation related to cobalamin activation, who are both of the same Native American tribal (non‐Athabascan) descent, display no ophthalmological symptoms. Findings from this study will expand the clinical understanding of this disease and will shed light on the impact of these conditions in minority populations. In addition, these results lay the foundation for future research examining associations between symptoms, symptom severity, and genetic analysis data. The ultimate goal of this research is to contribute to the Cobalamin activation section of a gene chip that addresses genetic disorders in Native Americans. Support or Funding Information Phoenix Children's Hospital