Tyrosinemia type 2 is an autosomal recessiveÂ disorder caused by mutations in the TAT gene (16q22.1) encoding tyrosine aminotransferase. Major clinical features include corneal lesions and hyperkeratotic skin plaques. In addition, there are well described neurological features including learning disabilities, tremor, ataxia and seizures. de Andrade et al. in Metab Brain Dis. 2011 Sep;26(3):221-7 offers in vitro and in vivo evidence to show that tyrosine inhibits creatine kinase in the cortex in a dose dependant manner, and they propose that this inhibition might contribute to the neurological phenotype of Tyrosinemia type 2. ThisÂ work offers a unique target for treatment, and further emphasizes the importance of understanding theÂ complex secondary biochemical effects of well described inborn errors of metabolism.
Hilary Vernon, MD PhD