*2.3.1 Disease mechanism*

The genetic cause of hyperprolinemia type 2 (HP2), first identified in an Irish traveler family [64], was found to be due to recessive mutations in *ALDH4A1.* The gene codes for pyrroline 5-carboxylate dehydrogenase (P5CD), an enzyme that catalyzes an intermediate step in the proline degradation pathway [6] (**Figure 7**). In a pathobiochemical mechanism similar to PDE-ALDH7A1, deficiency of P5CD leads to accumulation of pyrroline 5-carboxylate (P5C), an intermediate metabolite that undergo a spontaneous Knoevenagel type of reaction with PLP leading to reduced bioavailability of the cofactor (**Figure 7**) [63].
