PracticeUpdate Conference Series - SSIEM 2018

Follow-Up of Newborns With Suspected Lysosomal Storage Diseases Can Be Reduced Significantly With Simultaneous MS/MS and Confirmatory Tests Unneeded follow-up of these infants can beminimized.

S imultaneous determination of multiple enzyme activities by tandem mass spectrometry, adding specific biochemical markers as confirmatory tests, can significantly reduce fol- low-up of newborns with pseudodeficiency enzyme activities or carrier status, reports a tandemmass spectrometry investigation. AlbertoBurlina,MD, of theUniversitàdi Padova, Italy, andcolleagues set out to determine the activities of acid β-glucocerebrosidase (ABG; Gaucher disease), acid α-glucosidase (GAA, Pompe disease), acid α-galactosidase (GLA, Fabry disease), and acid α-L-iduronidase (IDUA, mucopolysaccharidosis I) in dried blood spots in a single assay at age of 48 h by multiplex tandem mass spectrometry using the NeoLSD® kit (Perkin Elmer). After methanolysis, biochemical confirmatory tests including assays of the following biomarkers were considered in patients who screened positive: Since 2015, 84,631 newborns have been screened. A total of 94 neonates (0.11%) have been recalled to donate a second dried blood spot. Low enzyme activities have been confirmed in 43 patients, who subsequently underwent the following confirmatory tests: ƒ ƒ LysoGb1 for Gaucher disease ƒ ƒ Glc4 for Pompe disease ƒ ƒ LysoGb3 for Fabry disease ƒ ƒ Urinary GAGs for mucopolysaccharidosis I Of these 43 patients, 15 exhibited abnormal biomarker values and mutational analyses confirmed disease presence. In 28 of the 43 patients, biomarkers were normal and mutational analysis showed pseudodeficiency or carrier status. Of note, the incidences of Pompe and Gaucher diseases were 1 in 21,158; of Fabry disease, 1 in 14,105; and of mucopolysaccharidosis, 1 in 42,316. The combined incidence of the four disorders was 1 in 5289 births. Dr. Burlina explained that the increasing availability of treatments and the importance of early intervention have stimulated newborn screening for lysosomal storage diseases. Early diagnosis of lysosomal storage diseases at the asymptomatic/presymptomatic stage is recognized as a valid ƒ ƒ Plasma glucosylsphingosine (LysoGb1) ƒ ƒ Lyso-globotriaosylceramide (LysoGb3) ƒ ƒ Urinary tetraglucoside (Glc4) ƒ ƒ Urinary glycosaminoglycans (GAGs)

public health objective. Inclusion of lysosomal storage diseases in newborn screening protocols is becoming more widespread internationally. Screening methods that provide a robust differentiation between affected and nonaffected individuals can help minimize false positives and avoid unnecessary treatment. Of the lysosomal storage diseases, Pompe disease and mucopolysaccharidoses I and II are the most favored for inclusion in screening programs. Fabry and Gaucher diseases are somewhat less favored. Krabbe disease is the least favored for newborn screening.

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PRACTICEUPDATE CONFERENCE SERIES • SSIEM 2018