Use of Tandem Mass Spectrometry for Newborn Screening of 6 Lysosomal Storage Disorders in a Korean Population

Abstract

BackgroundWe evaluated the performance of multiplex tandem mass spectrometry (MS/MS) in newborn screening for detection of 6 lysosomal storage disorders (LSDs), namely, Niemann-Pick A/B, Krabbe, Gaucher, Fabry, and Pompe diseases and Hurler syndrome.MethodsWe revised the conditions and procedures of multiplex enzyme assay for the MS/MS analysis and determined the precision of our enzyme assay and the effects of sample amounts and incubation time on the results. We also measured the degree of correlation between the enzyme activities in the dried blood spots (DBSs) and those in the leukocytes. DBSs of 211 normal newborns and 13 newborns with various LSDs were analyzed using our revised methods.ResultsThe intra- and inter-assay precisions were 2.9-18.7% and 8.1-18.1%, respectively. The amount of product obtained was proportional to the DBS eluate volume, but a slight flattening was observed in the product vs. sample volume curve at higher sample volumes. For each enzyme assay, the amount of product obtained increased linearly with the incubation period (range, 0-24 hr). Passing and Bablok regression analysis revealed that the enzyme activities in the DBSs and those in the leukocytes were favorably correlated. The enzyme activities measured in the DBSs were consistently lower in patients with LSDs than in normal newborns.ConclusionsThe performance of our revised techniques for MS/MS detection and enzyme assays was of the generally acceptable standard. To our knowledge, this is the first report on the use of MS/MS for newborn screening of LSDs in an Asian population.

Current status of newborn screening worldwide: 2015

“…There has also been increasing interest in NBS for LSDs, and significant progress with Pompe disease screening has been reported in Taiwan, [151][152][153] Japan, 154 and Korea. 155 Additional pilot studies in the region for other LSDs (Niemann-Pick A/B, Krabbe, Gaucher, Fabry, and Hurler syndrome) have been reported. [156][157][158][159] Other conditions for which there have been ongoing NBS pilot studies include citrin deficiency, 160 SCID, 161 Fragile-X syndrome, 162 X-ALD, 44 and Wilson's disease.…”

Newborn Screening for Lysosomal Storage Disorders in Hungary

“…As we found affected cases with an initial screening result close to the cutoffs for Pompe and Gaucher diseases (Table 6), we think we were at the very limit and further reduction would have resulted in missed diagnoses. Recently, Han et al (2011) reported a small-scale NBS for a Korean cohort, analyzing 211 normal newborns and 13 newborns with various LSDs to establish an NBS for LSDs in Korea; however, due to the small cohort no conclusion as to the prevalence of LSDs in Korea could be drawn. The data obtained by the newborn screening in Szeged is representative of the ethnicities found in the entire Hungarian population.…”

Levels of enzyme activities in six lysosomal storage diseases in Japanese neonates determined by liquid chromatography-tandem mass spectrometry

“…Using the MS/MS method, a Korean study also reported that the mean GAA activity of them was approximately 24 μmol/h/L [24]. Thus, higher GAA activity may be limited to Asian populations.…”