Two siblings with developmental delay, liver dysfunction and hypermethioninemia were investigated by exome sequencing. A homozygous missense mutation was identified in adenosine kinase, which could explain the block in the methionine cycle. Additional families were identified, and the mutations affected enzymatic function. The mouse deficient in adenosine kinase, described previously, displays phenotypic similarities, and to date there is no specific treatment modality. The pathophysiology of the disease is most likely complex, since both the accumulation of the substrate (adenosine) and the deficiency of the product (AMP) are expected to be detrimental.
Posted by Philippe Campeau, MD