Rapid chloride and bicarbonate determination by capillary electrophoresis for confirmatory testing of cystic fibrosis infants with volume-limited sweat specimens
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Universidade Federal de Minas Gerais
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Objectives Cystic fibrosis (CF) is a debilitating genetic disorder that benefits from early detection. CF diagnosis relies on measuring elevated sweat chloride that is difficult in neonates with low sweat rates. We introduce a new method for sweat chloride determination from volume-limited specimens, and explore the potential utility of sweat bicarbonate in neonatal CF screening. Methods A rapid assay (< 5 min) was developed to analyze chloride and bicarbonate using capillary electrophoresis with indirect UV detection (CE-iUV). Pilocarpine-stimulated sweat samples from screen-positive CF infants were collected at two hospital sites, including confirmed CF (n = 12), CF screen-positive inconclusive diagnosis (n = 4), and unaffected non-CF cases (n = 37). All sweat chloride samples were analyzed by a coulometric titrator and CE-iUV, and the viability to measure acid-labile bicarbonate was also evaluated. Results Stability studies revealed that bicarbonate can be reliably assessed in sweat if acidification and heating were avoided. Method validation demonstrated that sweat chloride and bicarbonate were quantified with acceptable accuracy (recovery of 102%), precision (CV = 3.7%) and detection limits (∼ 0.1 mM). An inter-laboratory comparison confirmed a mean bias of 6.5% (n = 53) for sweat chloride determination by CE-iUV relative to a commercial chloridometer. However, sweat bicarbonate did not discriminate between CF and non-CF infants (AUC = 0.623, p = 0.215) unlike chloride (AUC = 1.00, p = 3.00 × 10−7). Conclusions CE-iUV offers a robust method for sweat chloride testing from presumptive CF infants that may reduce testing failure rates. However, sweat bicarbonate does not have clinical value in newborn CF diagnosis.
Abstract
Assunto
Bicarbonato de sódio, Eletroforese capilar, Titração complexométrica, Glândulas sudoríparas, Fibrose cística, Recém-nascidos - Doenças, Cloretos
Palavras-chave
Bicarbonate, Capillary electrophoresis, Chloride, Coulometric titrationt, Confirmatory testing, Cystic fibrosis, Newborn screening, Pilocarpine iontophoresis, Swea
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https://www.sciencedirect.com/science/article/pii/S1569199322001126