Heterozygous mutations in the glucocerebrosidase gene (GBA) have been shown to be an important genetic risk factor for Parkinson\'s disease (PD) worldwide. However, the penetrance of GBA heterozygote for L444P, the common mutation for Asian population, is not known in older Chinese people.
To assess the conversion rate to PD in identified carriers of GBA L444P/R mutations in Chinese community-dwelling older adults.
The GBA gene was sequenced for mutations at position 444 in 8405 people older than 55 years who participated in the Beijing Longitudinal Study on Aging II cohort. Nine subjects were identified as heterozygous carriers of GBA L444P or L444R mutations at baseline and clinically followed up from 2009 to 2019 to investigate their PD conversion, motor and nonmotor symptoms, and change of vesicular monoamine transporter type 2 using tracer of [18 F]9-fluoropropyl-(+)-dihydrotetrabenazine (18 F-DTBZ, also known as 18 F-AV-133).
Eight heterozygous GBA L444P and 1 L444R mutation carriers were identified without PD at baseline, and none of them developed clinical parkinsonism after a 10-year follow-up.
Although GBA mutations may lead to an earlier onset PD, the majority of GBA L444P heterozygotes in older adults may not convert to PD. Further studies are warranted to identify factors that modify the risk of conversion. © 2020 International Parkinson and Movement Disorder Society.

BACKGROUND: Conventional screening tests to assess G6PD deficiency use a low cutoff value of 2.10 U/gHb which may not be adequate for detecting females with heterozygous deficiency. The aim of present study was to determine an appropriate cutoff value with increased sensitivity in identifying G6PD-deficient heterozygous females.
METHODS: G6PD activity analysis was performed on 51,747 neonates using semi-quantitative fluorescent spot test. Neonates suspected with G6PD deficiency were further analyzed using quantitatively enzymatic assay and for common G6PD mutations. The cutoff values of G6PD activity were estimated using the receiver operating characteristic curve.
RESULTS: Our results demonstrated that using 2.10 U/g Hb as a cutoff, the sensitivity of the assay to detect female neonates with G6PD heterozygous deficiency was 83.3%, as compared with 97.6% using 2.55 U/g Hb as a cutoff. The high cutoff identified 21% (8/38) of the female neonates with partial G6PD deficiency which were not detected with 2.10 U/g Hb. Our study found that high cutoffs, 2.35 and 2.55 U/g Hb, would increase assay\'s sensitivity to identify male and female G6PD deficiency neonates, respectively.
CONCLUSIONS: We established a reliable cutoff value of G6PD activity with increased sensitivity in identifying female newborns with partial G6PD deficiency.