title: PAS-positive lymphocyte vacuoles can be used as diagnostic screening test for Pompe disease.
abstract: Screening of blood films for the presence of periodic acid-Schiff (PAS)-positive lymphocyte vacuoles is sometimes used to support the diagnosis of Pompe disease, but the actual diagnostic value is still unknown. We collected peripheral blood films from 65 untreated Pompe patients and 51 controls. Lymphocyte vacuolization was quantified using three methods: percentage vacuolated lymphocytes, percentage PAS-positive lymphocytes, and a PAS score depending on staining intensity. Diagnostic accuracy of the tests was assessed using receiver operating characteristic (ROC) curves. All three methods fully discerned classic infantile patients from controls. The mean values of patients with milder forms of Pompe disease were significantly higher than those of controls, but full separation was not obtained. The area under the ROC curve was 0.98 for the percentage vacuolated lymphocytes (optimal cutoff value 3; sensitivity 91%, specificity 96%) and 0.99 for the percentage PAS-positive lymphocytes and PAS score (optimal cutoff value 9; sensitivity 100%, specificity 98%). Our data indicate that PAS-stained blood films can be used as a reliable screening tool to support a diagnosis of Pompe disease. The percentage of PAS-positive lymphocytes is convenient for use in clinical practice but should always be interpreted in combination with other clinical and laboratory parameters.
authors.affiliation: Department of Paediatrics, Division of Metabolic Diseases and Genetics, Erasmus MC University Medical Center- Sophia Children's Hospital, Rotterdam, The Netherlands. m.hagemans@erasmusmc.nl
authors.forename: Marloes L C
authors.initials: ML
authors.lastname: Hagemans
authors.forename: Rolinda L
authors.initials: RL
authors.lastname: Stigter
authors.forename: Carine I
authors.initials: CI
authors.lastname: van Capelle
authors.forename: Nadine A M E
authors.initials: NA
authors.lastname: van der Beek
authors.forename: Leon P F
authors.initials: LP
authors.lastname: Winkel
authors.forename: Laura
authors.initials: L
authors.lastname: van Vliet
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Arnold J J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: Auke
authors.initials: A
authors.lastname: Beishuizen
authors.forename: Ans T
authors.initials: AT
authors.lastname: van der Ploeg
mesh_terms: D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D056947:Enzyme Replacement Therapy; D004801:Eosine Yellowish-(YS); D005260:Female; D006003:Glycogen / Q000378:metabolism; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000188:drug therapy; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008403:Mass Screening / Q000379:methods* / Q000592:standards; D008751:Methylene Blue; D008875:Middle Aged; D010503:Periodic Acid-Schiff Reaction / Q000379:methods* / Q000592:standards; D012372:ROC Curve; D012680:Sensitivity and Specificity; D014617:Vacuoles / Q000378:metabolism / Q000473:pathology*; D055815:Young Adult
chemical_list: C043260:May-Grunwald Giemsa; D006003:Glycogen; D008751:Methylene Blue; D004801:Eosine Yellowish-(YS)