Ctsa, which encodes the protective protein/cathepsin A (PPCA), is crucial as mutations in this gene lead to secondary deficiency of β -galactosidase (GLB1) and neuraminidase 1 (NEU1), causing the lysosomal storage disorder galactosialidosis (GS) [1]. PPCA likely functions in maintaining the proper activity of these enzymes within the lysosome, and its role is vital for normal cellular metabolism and function related to lysosomal processes.

Analysis of Ctsa gene mutations in patients with GS has provided insights into the genotype-phenotype correlation. Three novel nucleotide changes were identified in four cases of the rare infantile form of GS, including two missense mutations (c.347A>G (p.His116Arg), c.775T>C (p.Cys259Arg)) and one nonsense mutation (c.1216C>T, resulting in p.Gln406* stop codon). An Italian founder effect of the c.114delG mutation was also suggested. In silico functional predictions of missense mutations helped predict different phenotypes of GS [1].

In conclusion, Ctsa is essential for preventing the lysosomal storage disorder galactosialidosis by maintaining the activity of key enzymes. Studies of Ctsa mutations in patients have enhanced our understanding of the genotype-phenotype relationship in GS, which is crucial for diagnosis and potentially future therapeutic strategies targeting this rare genetic disease.

References:

1. Caciotti, Anna, Catarzi, Serena, Tonin, Rodolfo, d'Azzo, Alessandra, Morrone, Amelia. 2013. Galactosialidosis: review and analysis of CTSA gene mutations. In Orphanet journal of rare diseases, 8, 114. doi:10.1186/1750-1172-8-114. https://pubmed.ncbi.nlm.nih.gov/23915561/