Introduction to the Newborn Screening, Diagnosis, and Treatment for Pompe Disease Guidance Supplement.

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* Abbreviations: ERT — : enzyme replacement therapy LSD — : lysosomal storage disorder NBS — : newborn screening Started in 1963 by Robert Guthrie, newborn screening (NBS) is considered to be one of the great public health achievements.1 The original goal of NBS was to screen newborns for conditions that could benefit from presymptomatic treatment and therefore reduce associated morbidity and mortality. As new methods became available that allowed for better screening of newborns (eg, tandem mass spectrometry), the scope of NBS broadened and the number of disorders included in NBS programs increased significantly.1,2 Lysosomal storage disorders (LSDs), which include >50 genetic disorders caused by dysfunctional or deficient activity of specific lysosomal enzymes, are good candidates for NBS.3–7 Pompe disease, a rare, autosomal recessive inherited LSD, is caused by mutations in the acid α-glucosidase ( GAA ) gene that lead to a deficiency of the lysosomal GAA enzyme. As a result, excess glycogen accumulates in many tissues throughout the body and causes cellular dysfunction and progressive damage to respiratory, cardiac, skeletal, and smooth muscle; considerable clinical debilitation; organ and system failure; and often death.8 There is a low index of clinical suspicion due to the rarity and heterogeneous nature of Pompe disease’s clinical presentation, often resulting in delays in diagnosis.9–11 The availability of a specific treatment for Pompe disease, namely enzyme replacement therapy (ERT) with alglucosidase alfa,12,13 that can treat this progressive disorder makes early diagnosis crucial, especially in infants with classic infantile-onset Pompe disease, the most … Address correspondence to Priya S. Kishnani, MD, Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, 595 LaSalle St, Durham, NC 27710. E-mail: priya.kishnani{at}duke.edu