Lysosomal dysfunction plays an important role in neurodegenerative diseases, including Parkinson’s disease (PD) and possibly Parkinson-plus syndromes such as progressive supranuclear palsy (PSP). This role is exemplified by the involvement of variants in the GBA1 gene, which results in a deficiency of the lysosomal enzyme glucocerebrosidase and is the most frequently identified genetic factor underlying PD worldwide. Pathogenic variants in the SMPD1 gene are a recessive cause of Niemann–Pick disease types A and B. Here, we provide the first report on an association between a loss-of-function variant in the SMPD1 gene present in a heterozygous state (p.Pro332Arg/p.P332R, which is known to result in reduced lysosomal acid sphingomyelinase activity), with PSP-Richardson syndrome in three unrelated patients of Chinese ancestry.

Humans ; Peritoneal Dialysis ; Renal Dialysis

Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally and its prevalence in Singapore is expected to increase exponentially with our ageing population. Diagnostic and management issues unique to the elderly population will be discussed broadly in this topic review.

Air Pollutants ; Air Pollution ; China ; Health Knowledge, Attitudes, Practice ; Humans ; Perception ; Seasons

Parkinson’s disease (PD) is the second most common neurodegenerative disorder globally and its prevalence in Singapore is expected to increase exponentially with our ageing population. Diagnostic and management issues unique to the elderly population will be discussed broadly in this topic review.

Background: Impulse control behaviours are repetitive and excessive activities that may be subsyndromal and not fulfil the criteria for impulse control disorder. These activities have potential to negatively impact on the daily lives of sufferers. We conducted a study to investigate the prevalence of impulse control behaviours and its associated features in Parkinson’s disease in our population. Methods: We conducted a prospective cross-sectional study on consecutive patients attending neurology clinic. Inclusion criteria include idiopathic Parkinson’s disease patients with Hoehn & Yahr stage I-IV. Eighty patients were enrolled and screened for impulse control behaviours using the Questionnaire for Impulsive-Compulsive Disorder for Parkinson’s disease (QUIP). Results: Prevalence of impulse control behaviours among our cohort was 11.3%; the features significantly associated with it were higher level of education (p=0.02), advanced stage of disease (p=0.03) and higher levodopa dosage (p= 0.01). The commonest impulse control behaviour in our cohort was compulsive medication use (7.5%), followed by hobbyism (6.3%), hypersexuality (5%), compulsive buying (3.75%), punding (2.5%), walkabout (2.5%), compulsive eating (1.25%) and pathological gambling (1.3%). Conclusions: There is an association between impulse control behaviour and higher levodopa dosage in a study on patients with Parkinson’s disease in Malaysia. We also found a low prevalence of pathological gambling as compared to studies performed in the West.
Disruptive, Impulse Control, and Conduct Disorders ; Parkinson Disease

Genetic Markers ; Genome-Wide Association Study ; HLA-DQ Antigens ; genetics ; HLA-DR Antigens ; genetics ; Humans ; Inflammation ; complications ; genetics ; pathology ; Parkinson Disease ; diagnosis ; genetics ; pathology ; Risk Factors ; Time Factors

Genome-Wide Association Study ; standards ; Humans

The recent identification of a common genetic variant (LRRK2 G2385R) which is associated with a two-fold increased risk of sporadic Parkinson's Disease (PD) in two independent Chinese populations in Singapore and Taiwan has generated considerable excitement. Thus far, this variant appears specific for the Asian population, emphasising further that ethnic-specific effects should be considered in genetic association studies. Cautious optimism is advised as we await more scientific studies and clarification if this risk variant is specific to ethnic Chinese race. Our in-vitro studies suggest the Gly2385Arg variant is biologically relevant and it might act through pro-apoptotic mechanisms, especially under cellular stresses. This may provide a partial explanation why some carriers develop the disease while others do not. The presence of other epigenetic factors, gene-gene and gene-environmental interaction could modulate the phenotype expression. Further validation of these findings would be needed to confirm this variant as the single most important common genetic risk factor in ethnic Chinese and/or Asian PD patients. The identification of the LRRK2 Gly2385Arg variant could potentially facilitate the development of clinical, bioimaging, genetic and biological biomarkers, useful in the monitoring and neuroprotective therapy in asymptomatic individuals.
Asian Continental Ancestry Group ; Biomarkers ; DNA ; genetics ; Genetic Predisposition to Disease ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 ; Mutation ; Parkinson Disease ; ethnology ; genetics ; Prevalence ; Protein-Serine-Threonine Kinases ; genetics ; Risk Factors ; Singapore ; epidemiology ; Taiwan ; epidemiology