Establishing Pompe Disease Newborn Screening: The Role of Industry

When clinical trials for enzyme replacement therapy for Pompe disease commenced, a need for newborn screening (NBS) for Pompe disease was recognized. Two methods for NBS for Pompe disease by measuring acid α-glucosidase in dried blood spots on filter paper were developed in an international collaborative research effort led by Genzyme. Both methods were used successfully in NBS pilot programs to demonstrate the feasibility of NBS for Pompe disease. Since 2009, all babies born in Taiwan have been screened for Pompe disease. Pompe disease was added to the Recommended Uniform (Newborn) Screening Panel in the United States in 2015. NBS for Pompe disease is possible because of the unprecedented and selfless collaborations of countless international experts who shared their thoughts and data freely with the common goal of establishing NBS for Pompe disease expeditiously

Improved sensitivity of an acid sphingomyelinase activity assay using a C6:0 sphingomyelin substrate

Short-chain C6-sphingomyelin is an artificial substrate that was used in an acid sphingomyelinase activity assay for a pilot screening study of patients with Niemann–Pick disease types A and B. Using previously published multiplex and single assay conditions, normal acid sphingomyelinase activity levels (i.e. false negative results) were observed in two sisters with Niemann–Pick B who were compound heterozygotes for two missense mutations, p.C92W and p.P184L, in the SMPD1 gene. Increasing the sodium taurocholate detergent concentration in the assay buffer lowered the activity levels of these two patients into the range observed with other patients with clear separation from normal controls

The Identification of New Biomarkers for Identifying and Monitoring Kidney Disease and Their Translation into a Rapid Mass Spectrometry-Based Test: Evidence of Presymptomatic Kidney Disease in Pediatric Fabry and Type‑I Diabetic Patients

Using label-free quantative proteomics, we have identified 2 potential protein biomarkers that indicate presymptomatic kidney disease in the urine of pediatric patients with type-I diabetes and Fabry disease (<i>n</i> = 20). Prosaposin and GM₂ activator protein (GM₂AP) were observed to be elevated in the urine of these patient groups compared to age- and sex-matched controls. These findings were validated by development of a rapid MRM-based tandem mass spectrometry test. Prosaposin was observed to be both significantly elevated in the urine of patients with Fabry disease compared to controls (<i>p</i> = 0.02) and reduced after 12 months enzyme replacement therapy (ERT, <i>p</i> = 0.01). Similarly, GM₂AP concentrations were observed to be significantly higher compared to controls in the diabetic group (<i>p</i> = 0.049) and the pretreatment Fabry group (<i>p</i> = 0.003). In addition, this observed to be reduced significantly in the Fabry group following 12 months of ERT (<i>p</i> = 0.01). The process of detection of the biomarkers, development into a test and implications for monitoring patients and treatment are discussed

Additional file 1: of Diagnosis of late-onset Pompe disease and other muscle disorders by next-generation sequencing

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