The factors and mechanisms underlying these differences remain unknown. Nonetheless, it is noteworthy that total circulating leptin levels are lower and soluble leptin receptor levels are higher in the subject with the most severe phenotype. We speculate that differences in free circulating leptin could determine clinically significant divergent metabolic phenotype among these patients with CGL1. It is also notorious that, in contrast to previously reported CGL cases, patient 1 has no evidence of fatty liver disease. We propose that this might result from the combined effect of low dietary fat intake and low insulin driven hepatic de novo lipogenesis. There were statistically significant differences in dopamine synthesis capacity among striatal subregions. A previous postmortem report showed the distribution of dopamine transporter in the striatum to differ, based on the regional dependencies of the dopamine D1, D2 and D3 receptors. There are several reports Gomisin-D suggesting the relation of subregional dopaminergic function in the striatum with psychiatric disorders and with cognitive function. As with distributions of dopamine transporter and receptors, distribution of dopamine synthesis capacity might be relevant to the interpretation of neurological function and psychiatric disorders. The difference of diffusion metrics among subregions may reflect cellular-level structural difference of these functionally different cells. Actually, immunohistological study on postmortem human brain has demonstrated that the architecture of the human striatum in terms of its interneuron composition varies in functional territories. FA had a significant positive correlation with age in PCN in this study. The other regions, while not statistically significant, also showed positive correlations. Similar results were also reported in a number of other studies for 0.758, 0.685 and 0.667 of correlation coefficients was 0.794, 0.649 and 0.613, respectively, for the hypothesis that the correlation between R and MD is 0 in 10 subjects. Thus, the present results have a little higher second type of statistical error. Actually, we could not find an age-related decline of dopamine synthesis in ST, as previously reported. In addition, the physiological 
background of DTI metrics in gray matter is still controversial. However, there is no question that these metrics reflect water motions restricted by the cell-level structure of tissue. The new diffusion MRI, such as Q-space imaging and diffusion kurtosis imaging, with a high magnetic field scanner may provide more detailed information. The insufficient spatial resolution of PET is also a critical issue in respect to the reliability of the present results. Actually, R of PCN ROI is lower than that of the others due to the thin-tube-like shape. However, specific binding of radiotracers is not observed in tissues surrounding the ST, which means that the PET pixel intensity of the PCN region is not contaminated by radioactivity of surrounding tissues. The PET and DTI scanner with higher spatial resolution and sensitivity will resolve this issue as well as enable us to perform more detailed analyses of the central dopaminergic system, e.g., analysis of PET/ DTI relations on nigrostriatal pathways and cerebral cortical regions including the limbic system by measuring the small substantia nigra and cerebral cortex expressing small amounts of AADC. Cadmium is a toxic heavy metal with a variety of sources in the environment and from industry including use in electroplating, paint and mining. It is also associated with waste water pollution, and its discharge into water and food resulting in Eleutheroside-E adverse effects on living organisms and the environment. Cadmium has a long biological half-time of 10�C30 years in human kidney.