Objective: To report and discuss two unrelated patients carrying heterozygous mutations in both Parkin (PARK2) and Glucocerebrosidase (GBA) gene, with atypical Parkinsonian features.

Background: Parkin (PARK2) gene is the main cause of autosomal recessive forms of early-onset parkinsonism, with atypical clinical signs but characterized by a benign evolution. Also, when pathogenic GBA mutations are inherited in a autosomal dominant form, consist a strong risk factor for typical PD. We discuss the contribution of these two coexistent mutations in two patients with an atypical phenotype.

Methods: Case-report of two patients. Genetic studies were performed with direct sequenciation of GBA and PARK2 gene, and genic dosage of PARK2 gene.

Results: A 62-year-old female patient was observed in our outpatient clinic, with a prior diagnosis of PD. First motor symptoms were traced back to 57-years old. She presents a severe, predominantly left bradykinetic parkinsonism, with motor fluctuations (off-periods with intense pain and dystonia, sometimes with dysautonomic features, and delayed on phenomena), ocular apraxia and severe behavioural features. She is currently under medication with levodopa and rotigotine. Genetic study revealed a GBA mutation (Asn370Ser) and a PARK2 mutation (p.Arg402Cys), both in heterozigoty. One other female patient developed a right-side parkinsonism at age 69, without features suggestive of parkinonism “plus” (namely a favourable levodopa response). At age 73, she progressively worsened her parkinsonism, and develops severe apathy and cognitive dysfunction with frontal features. She died at age 76, presenting mutism and a severe malnutrition status. Genetic study revealed a GBA mutation (Leu444Pro) and a PARK2 mutation (Arg334Cys), both in heterozigoty.

Conclusions: These patients reveal a late-onset parkinsonism, with rapid evolution and neuropsychiatric features. We hereby discuss the role of the identified mutations in the atypical phenotypes presented.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/two-cases-of-parkinsonism-with-atypical-genetics/