Prodromal substantia nigra sonography undermines suggested association between substrate accumulation and the risk for GBA-related Parkinson's disease.

BACKGROUND AND PURPOSE: Individuals with GBA (glucocerebrosidase) mutations are at increased risk of Parkinson's disease (PD). It is still debated, however, whether this increased risk results from impaired glucocerebrosidase activity leading to substrate accumulation. Comparing the presence of prodromal PD marker in GBA mutation carriers and patients with Gaucher disease (GD) (in which substrate accumulation is extensive) can assist in clarifying this issue. METHODS: In this cross-sectional study, we compared the hyperechogenic area of the substantia nigra, a prodromal PD marker, in large cohorts of GBA mutation carriers (n = 71) and patients with GD (n = 145). Our control populations were healthy, non-carriers (n = 49) and patients with GBA -related PD (n = 11). Substrate accumulation was assessed from dry blood spot levels of glucosylsphingosine. RESULTS: Our findings indicate no contribution of substrate accumulation, as the area of hyperechogenicity is similarly enlarged relative to healthy controls in both GBA mutation carriers and patients with GD. Moreover, this similarity between GBA carriers and patients with GD persists when comparing only carriers of the N370S (c.1226A>G) mutation (n = 38) with untreated patients with GD who were homozygotes for the same mutation (n = 47). In addition, measurements of hyperechogenic area did not correlate with levels of glucosylsphingosine in the untreated patients with GD. CONCLUSION: The presence of a marker of prodromal PD (substantia nigra hyperechogenicity) is independent of substrate accumulation in a population with mutated GBA . Although further longitudinal studies are needed to determine the precise predictive value of this marker for GBA -related PD, our findings raise doubts regarding the contribution of substance reduction strategies to PD prevention.

Anthropometric adjustments are helpful in the interpretation of BMD and BMC Z-scores of pediatric patients with Prader-Willi syndrome.

Anthropometric adjustments of bone measurements are necessary in Prader-Willi syndrome patients to correctly assess the bone status of these patients. This enables physicians to get a more accurate diagnosis of normal versus abnormal bone, allow for early and effective intervention, and achieve better therapeutic results. INTRODUCTION: Bone mineral density (BMD) is decreased in patients with Prader-Willi syndrome (PWS). Because of largely abnormal body height and weight, traditional BMD Z-scores may not provide accurate information in this patient group. The goal of the study was to assess a cohort of individuals with PWS and characterize the development of low bone density based on two adjustment models applied to a dataset of BMD and bone mineral content (BMC) from dual-energy X-ray absorptiometry (DXA) measurements. METHODS: Fifty-four individuals, aged 5-20 years with genetically confirmed PWS, underwent DXA scans of spine and hip. Thirty-one of them also underwent total body scans. Standard Z-scores were calculated for BMD and BMC of spine and total hip based on race, sex, and age for all patients, as well as of whole body and whole-body less head for those patients with total-body scans. Additional Z-scores were generated based on anthropometric adjustments using weight, height, and percentage body fat and a second model using only weight and height in addition to race, sex, and age. RESULTS: As many PWS patients have abnormal anthropometrics, addition of explanatory variables weight, height, and fat resulted in different bone classifications for many patients. Thus, 25-70 % of overweight patients, previously diagnosed as normal, were subsequently diagnosed as below normal, and 40-60 % of patients with below-normal body height changed from below normal to normal depending on bone parameter. CONCLUSIONS: This is the first study to include anthropometric adjustments into the interpretation of BMD and BMC in children and adolescents with PWS. This enables physicians to get a more accurate diagnosis of normal versus abnormal BMD and BMC and allows for early and effective intervention.