Sepiapterin reductase deficiency: two Indian siblings with unusual clinical features.

clinical symptoms of all MC were in line with classical PD. For comparison of AAO data, we used published AAO of a large population-based cohort. The AAO of 197 idiopathic PD patients was 70 6 11 years, whereas the AAO of MC with one mutation in our meta-analysis was 42 6 16 years (P < 0.0001). It should be noted however, patients with young onset of PD are more likely to be included in genetic studies, leading to a bias in the observed AAO. In the present meta-analysis, MC with two mutations had a significantly earlier AAO, possibly indicating a dose effect of the mutation. These findings had not yet been demonstrated for PINK1, however, a similar effect is known for Parkin, another recessive PD gene. In conclusion, (1) two mutations within PINK1 lead to a decreased AAO compared to one mutation; (2) the clinical picture is otherwise independent of the number of mutated alleles and comparable to that of idiopathic PD.