Acid sphingomyelinase deficiency (ASMD) is currently treatable with olipudase alfa, increasing the need for early newborn screening (NBS). We conducted a two-center pilot cohort study to characterize dried blood spot (DBS) acid sphingomyelinase (ASM) activity in Japanese neonates in the neonatal intensive care unit (NICU). ASM activity was measured by flow injection-tandem mass spectrometry in 244 NICU-admitted neonates (gestational age 25–41 weeks; birth weight 773–4201 g); longitudinal paired samples were available in 34 neonates with birth weight < 2000 g and concurrent hematology in 43 neonates. The mean ASM activity was 3.7 ± 1.2 μmol/h/L (95% confidence interval, 3.54–3.84; range, 1.7–11.6), with a right-skewed distribution. ASM activity correlated positively with birth weight (r = 0.184, p = 0.0039), gestational age (r = 0.219, p = 0.0006), and lymphocyte count (ρ = 0.394, p = 0.0089) and negatively with hematocrit (ρ = −0.372, p = 0.014). In neonates with a birth weight < 2000 g, ASM increased significantly on repeat sampling (mean difference, 1.60 μmol/h/L; p < 0.0001; Cohen’s d = 0.912). These findings support NICU-specific reference ranges, hematology-informed interpretations, repeat testing after maturation, and the use of second-tier biomarkers for ASMD NBS implementation in Japan.

Background: Pyruvate dehydrogenase kinase isoform 4 (PDK4) plays a pivotal role in the regulation of cellular proliferation and apoptosis. The objective of this study was to examine whether the genetic depletion of the PDK4 gene attenuates hyperoxia-induced lung injury in neonatal mice. Methods: Neonatal PDK4−/− mice and wild-type (WT) mice were exposed to oxygen concentrations of 21% (normoxia) and 95% (hyperoxia) for the first 4 days of life. Pulmonary histological assessments were performed, and the mRNA levels of lung PDK4, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 were assessed. The levels of inflammatory cytokines in lung tissue were quantified. Results: Following convalescence from neonatal hyperoxia, PDK4−/− mice exhibited improved lung alveolarization. Notably, PDK4−/− mice displayed significantly elevated MCP-1 protein levels in pulmonary tissues following 4 days of hyperoxic exposure, whereas WT mice showed increased IL-6 protein levels under similar conditions. Furthermore, neonatal PDK4−/− mice subjected to hyperoxia demonstrated markedly higher MCP-1 mRNA expression at 4 days of age compared to WT mice, while IL-6 mRNA expression remained unaffected in PDK4−/− mice. Conclusions: Newborn PDK4−/− mice exhibited notable recovery from hyperoxia-induced lung injury, suggesting the potential protective role of PDK4 depletion in mitigating lung damage.

Background: Gaucher disease (GD) and acid sphingomyelinase deficiency (ASMD) are rare lysosomal storage diseases with thrombocytopenia and splenomegaly. We evaluated targeted dried blood spot (DBS) screening in Japan.,Methods: Participants from 180 facilities with unexplained thrombocytopenia and/or splenomegaly were enrolled. DBS specimens were collected between August 2017 and May 2024. Glucosylceramidase beta (GBA) activity was measured using a fluorometric assay. Participants with low activity provided a second DBS specimen, and GBA sequencing was performed if repeat results were low. Acid sphingomyelinase (ASM) activity was measured using 6-plex flow injection tandem mass spectrometry.,Results: Among 611 screened participants, 57 had low GBA activity initially. Thirty-one provided a second DBS; 28 had higher than cutoff values, and three remained low in the second test. GBA sequencing in these three revealed pathogenic variants homozygous or compound heterozygous, and all were diagnosed with GD. All three had thrombocytopenia and splenomegaly, including a history of massive splenomegaly before splenectomy in one adult. The GD detection rate was 0.49% (3/611; 95% CI, 0.10–1.43%), with the dropout-adjusted estimate at 0.90% (95% CI, 0.40–2.02%). For ASMD screening, 532 stored DBS specimens were analyzed. Low ASM activity was observed in 24 specimens, all also had low alpha-galactosidase A activity, and some had additional low enzyme activities. No ASMD cases were diagnosed.,Conclusions: Targeted DBS screening identified undiagnosed GD in this high-risk Japanese cohort. Thrombocytopenia and splenomegaly may enrich screening populations. Stored specimens require careful assessment of quality for additional enzyme assays.