ISYNA1 and thanatophoric dysplasia: In this respect, a role for altered MI signaling in TD is also implicated by the fact that some key enzymes involved in the synthesis of MI were found to be differentially expressed in the brain and/or blood of TD patients: HK2 (increased in the postmortem striatum of TD patients [64], ISYNA1 (an enzyme that catalyzes the rate-limiting step in MI synthesis and of which the expression was downregulated in the blood of TD patients aged 5–9 and 13–16 [66]) and the landscape protein IMPA1 (upregulated in the blood of TD patients aged 10–12 [66]).