ORIGINAL ARTICLE Cognitive decline and depressive symptoms: early non-motor presentations of parkinsonism among Egyptian Gaucher patients Azza Abdel Gawad Tantawy 1 & Amira Abdel Moneam Adly 1 & Mai Seif El Din Abdeen 2 & Nouran Yousef Salah 1 Received: 2 December 2019 /Accepted: 13 March 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020 Abstract Evidence about the link between glucocerebrosidase (GCase) and parkinsonism is growing. Parkinsonism was described in adult type 1 Gaucher disease (GD); few case reports described it in type 3GD. To assess the presence of parkinsonian features in a cohort of Egyptian GD patients and correlate these findings to their genotype, phenotype, severity scoring index (SSI), cognitive function, and the presence of depressive symptoms. Twenty-four GD patients from the Pediatric Hematology Clinic, Ain Shams University, were assessed for medication history, neurological symptoms, depressive symptoms, and family history of parkin- sonism. Anthropometric measures, complete neurological assessment, and SSI were examined. Neuropsychiatric evaluation included parts I, II, III, and V of the Unified Parkinson’ s Disease Rating Scale (UPDRS), Beck Depression Inventory (BDI), and Wechsler Intelligence Scale for Children (WISC-children). Molecular analysis of the acid GBA gene was performed, and SSI was calculated. Sixteen GD patients (66.6%) had parkinsonian features with a male to female ratio of 1:1. Their mean age was 15.69 ± 5.62 (range, 12–26). They were all on enzyme replacement therapy (ERT) with a dose of 60 U/kg/2 weeks. Twelve GD patients were phenotypically type 3 (75%). Thirteen GD patients with parkinsonian features (81.25%) had L483P mutation. GD patients with parkinsonian features had higher SSI (P < 0.001), lower cognitive functions (P = 0.007), and more significant depressive symptoms (P = 0.031). Logistic regression analysis revealed that GD genotype (P = 0.003), GD type (P = 0.006), and cognitive functions (P = 0.03) were the only significant independent factors for the development of parkinsonian features among GD patients. With the increased life span and improved somatic manifestations of type 3GD on ERT, these patients can live to develop parkinsonism. Cognitive decline and depression can be early predictors of parkinsonism among GD population. Keywords Parkinsonian features . Gaucher . Depressive symptoms Abbreviations GD Gaucher disease GCase Glucocerebrosidase SSI Severity scoring index UDPRS Unified Parkinson’ s Disease Rating Scale BDI Beck Depression Inventory WISC-children Wechsler Intelligence Scale for Children SPSS Statistical Package for Social Science SD Standard deviation NMS Non-motor symptoms Introduction Evidence about the link between the lysosomal enzyme glucocerebrosidase (GCase) and parkinsonism is growing. Hints of this relationship came from sporadic cases and small cohorts of patients with Gaucher disease (GD) and parkinson- ism [1, 2]. The GBA gene is located at chromosome 1q21, and it codes for the beta-glucocerebrosidase enzyme. Mutations in GBA gene result in reduction or elimination of GBA activity, causing glucocerebroside to accumulate in lysosomes of af- fected organs [3]. Homozygous GBA mutation develops GD while heterozygous GBA mutation does not develop GD, but is at an increased risk for parkinsonism. It should be noted that not all GBA mutation carriers develop parkinsonism. Thus, there is an association between the GBA mutation and parkin- sonism, but the exact pathophysiological mechanism behind GBA-associated parkinsonism remains unraveled. * Nouran Yousef Salah niron85@hotmail.com 1 Pediatrics Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt 2 Psychiatry Department, Faculty of Medicine, Ain Shams University, Cairo, Egypt neurogenetics https://doi.org/10.1007/s10048-020-00607-4