Abstract
Parkinson's disease (PD) is a common neurodegenerative disorder, and pathogenic variants in
GBA1
are among its most frequent genetic risk factors. Biallelic pathogenic
GBA1
variants cause Gaucher Disease (GD). In patients with parkinsonism and two detected
GBA1
variants, the absence of biochemical confirmation and allele phasing may make it difficult to determine whether the neurological presentation occurs in the context of GD or represents
GBA1
-associated PD. We report a 35-year-old man with a 7-months history of progressive, asymmetric parkinsonism. Dopamine transporter PET/CT showed reduced bilateral striatal uptake, more pronounced on the right. Abdominal CT showed asplenia, and laboratory eveluation revealed mild thrombocytopenia, marked hyperferritinemia, polyclonal hypergammaglobulinemia, proteinuria, and microscopic hematuria. Whole-exome sequencing followed by Sanger validation identified two heterozygous
GBA1
variants classified as pathogenic: c.1448T>C (p.Leu483Pro; legacy name L444P) and c.1342G>C (p.Asp448His; legacy name D409H). Family testing supported the familial occurrence of both variants but did not establish their allelic phase. Because glucocerebrosidase activity and GD biomarkers were not measured, type 1 Gaucher disease (GD1) remained suspected rather than confirmed. During hospitalization, dopaminergic therapy was associated with clinical improvement, with the OFF-state UPDRS-III score decreasing from 21 at admission to 10 at discharge. The clinical value of this case lies in the convergence of early-onset parkinsonism, remote visceral and hematologic findings, the co-occurrence of p.Leu483Pro and p.Asp448His with unresolved allelic phase, and the familial occurrence of both variants. It underscores the need for biochemical confirmation,
GBA1
-specific phase-resolved testing, and longitudinal multisystem assessment before the diagnosis of GD1 and the associated familial risks can be reliably defined.