Molecular basis of Dihydropterine Reductase Deficiency.

Dihydropteridine reductase (DHPR) deficiency is an inherited disease characterized by hyperphenylalaninemia unresponsive to a phenylalanine-restricted diet and by progressive neurological deterioration. The disorder is heterogeneous both clinically (different response to therapy), and biochemically (different amounts of enzyme residual activity). As expected, many different mutations have been identified in the gene encoding for DHPR. Most of them are point mutations. So far 15 mutations have been identified. The molecular effect of some mutations, inferred on the basis of the nature of the mutation, its localization and analysis of expression studies, will be discussed.