The erythrocyte osmotic resistance test as screening tool for cholesterol-related lysosomal storage diseases

• Published in: Clinica chimica acta 2018-05, Vol.480, p.161-165
• Main Authors: López de Frutos, Laura, Cebolla, Jorge J., Irún, Pilar, Köhler, Ralf, Giraldo, Pilar
• Format: Article
• Language: English
• Subjects: Cholesterol-related lysosomal diseases; Lysosomal acid lipase deficiency; Niemann Pick type C; Osmotic haemolysis; Screening test
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/j.cca.2018.02.010

Erythrocyte volume regulation and membrane elasticity are essential for adaptation to osmotic and mechanical stress, and life span. Here, we evaluated whether defective cholesterol trafficking caused by the rare lysosomal storages diseases (LSDs), Niemann-Pick type C (NPC) and Lysosomal acid lipase (LAL) deficiency (LALD) impairs these properties. Moreover, we tested whether measurements of cholesterol membrane content and osmotic resistance serve as a screening test for these LSDs. Patients were genotyped for mutations in NPC1, NPC2, or LIPA genes. We measured LSD plasma biomarkers and LAL activity. Red blood cells (RBC) membrane cholesterol content was evaluated in 73 subjects. Osmotic resistance tests (ORT) were conducted in 121 blood samples from LSD suspected patients and controls. We did not find statistically significant differences between RBC cholesterol content between subjects and controls. However, the ORT, particularly at 0.49% (w/v) hypotonic sodium chloride solution, revealed a significant higher osmotic resistance in LSDs patients than in controls. We established a cut-off value of ≤51% of haemolysis with sensibility and specificity values of 80% and 70%, respectively. NPC and LALD do not alter cholesterol content in the RBC membrane but increase osmotic resistance. Therefore, ORT serves as screening test for the studied LSDs. •The osmotic resistance test is useful as a screening test for lysosomal storage diseases related to cholesterol trafficking.•To complete the study for LSDs is important in those subjects with haemolysis values at 0.49% NaCl concentration under the established cut-off.•Significant differences have not been observed in the erythrocite's membrane cholesterol concentration between patients and controls.