Although Batten disease, also known as CLN3 disease, and Niemann-Pick disease, type C1 (NPC1 disease) exhibit similar clinical and cellular characteristics, both being lysosomal storage disorders, their progression and underlying pathophysiology vary. Analyzing proteomic findings may uncover shared and unique markers suitable for newborn screening and disease monitoring. CLN3 is an autosomal recessive, fatal, neurodegenerative disease. The typical childhood presentation encompasses vision loss, neurocognitive impairments, and seizures. NPC1 is also a neurodegenerative disorder inherited through an autosomal recessive pattern. It stems from various potential mutations in the NPC1 gene, leading to the buildup of unesterified cholesterol and glycosphingolipids in late endosomes and lysosomes. NPC1 patients are also pediatric and may exhibit clinical complications associated with jaundice, enlarged spleen, and trouble swallowing, leading to death. Proximal extension assay (PEA) of 1467 proteins generated a list of potential proteomic biomarkers from cerebrospinal fluid (CSF) samples of 28 individuals with CLN3, 28 with NPC1, and 32 unaffected samples as a comparison cohort made of pediatric laboratory control (PLC) (n=10), creatine transporter deficiency (CTD) (n=12), and Smith-Lemli-Opitz syndrome (SLOS) (n=10). We compared the potential proteomic biomarkers in the CSF of patients with CLN3 and NPC1 disease. At an adjusted p-value of <0.10, 11 proteins in CLN3 exhibited increased expression compared to NPC1, while 139 showed decreased expression. At an adjusted p-value of < 0.10 and absolute log2 fold change ≥ 1.0, four proteins (CD36, FBP1, CTSH, and MEPE) in CLN3 had an increased expression compared to NPC1. With the same parameters, 17 proteins were significantly downregulated in CLN3 in comparison to NPC1, including CCL18, CD302, and SNCG. Proteins will be investigated with a threshold of an adjusted p-value <0.10 and an absolute log2 fold change >0.58, corresponding to a fold change > 1.5, in CLN3 versus NPC1, CLN3 versus comparison cohort, and NPC1 versus comparison cohort. Further examination will delve into comparing the proteins in CLN3 versus the comparison cohort and NPC1 versus the comparison cohort. Furthermore, an analysis will investigate the pathways in which these proteins participate, exploring potential links with the pathology of CLN3 and NPC1. This endeavor aims to suggest novel proteomic biomarkers for these conditions.
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