Objective: To report a case of a probable association between a mutation in the BSCL2 gene (Berardinelli-Seip Congenital Lipodystrophy 2) and Parkinson’s disease (PD).

Background: The BSCL2 gene encodes the protein seipin [1]. Seipin plays a crucial role in lipid metabolism by participating in lipid droplet (LD) homeostasis [2-4]. LDs are organelles that store and release triacylglycerols according to the body’s needs, but they also function as signaling centers,  inflammation markers, and cellular aging indicators [5-10].

Virtually all types of brain cells form LDs [6]. Alterations in the lipid composition of central nervous system cells affect cell function and normal neuronal activity [11-12]. Lipid dysregulation has been identified as a feature of neurodegenerative diseases [6].

Alterations in lipid metabolism are associated with an increased risk of PD. Lipid and lipoprotein signaling are regulated by the same processes involved in the death of dopaminergic neurons. Lewy bodies accumulate on the surfaces of LDs, slowing their lipolysis [13-15].

Method: An 83-year-old female patient who has been under follow-up for essential tremor (ET) and PD for 33 years at a referral center in Mexico. She reported living in an urban environment and denied significant environmental exposures. She has several family members diagnosed with PD. Her family tree is shown in Figure 1.

Results: At 49 years, she began experiencing resting and postural tremors of 4-6 Hz, 0.5 cm amplitude in both hands, discrete, non-progressive, exacerbated by stress, and attenuated by sleep and activity, without functional impairment, accompanied by peribuccal paresthesias. It was diagnosed as ET. Her evolution and management are summarized in Figure 2.

At 78 years, she was diagnosed with RBD, in addition to an increase in her tremor, along with bradykinesia. On examination, there was bilateral bradykinesia and mild resting and postural tremor, with left-side predominance (UPDRS III = 22 points). 18 F-DTBZ PET/CT showed a loss of integrity in the nigrostriatal system (mixed type), leading to the diagnosis of PD. A genetic study revealed a heterozygous mutation in the BSCL2 gene, in the variant c.175A>T (p.Thr59Ser).

Conclusion: These findings open new avenues for a better understanding of the pathophysiology of neurodegenerative diseases and could offer potential therapeutic targets in the future. It is necessary to search for the BSCL2 gene mutation in the remaining relatives.

Figure 1. Patient’s Genealogy Tree.

Figure 2. Natural History and Management

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MDS Abstracts - https://www.mdsabstracts.org/abstract/implications-of-bscl2-mutation-in-the-pathogenesis-of-parkinsons-disease/