OBJECTIVE. Pompe disease is an autosomal recessive lysosomal storage disorder that is caused by deficient acid α-glucosidase activity and results in progressive, debilitating, and often life-threatening symptoms involving the musculoskeletal, respiratory, and cardiac systems. Recently, enzyme replacement therapy with alglucosidase α has become possible, but the best outcomes in motor function have been achieved when treatment was initiated early. The aim of this study was to test the feasibility of screening newborns in Taiwan for Pompe disease by using a fluorometric enzymatic assay to determine acid α-glucosidase activity in dried blood spots. METHODS. We conducted a large-scale newborn screening pilot program between October 2005 and March 2007. The screening involved measuring acid α-glucosidase activity in dried blood spots of ∼45% of newborns in Taiwan. The unscreened population was monitored as a control. RESULTS. Of the 132 538 newborns screened, 1093 (0.82%) repeat dried blood-spot samples were requested and retested, and 121 (0.091%) newborns were recalled for additional evaluation. Pompe disease was confirmed in 4 newborns. This number was similar to the number of infants who received a diagnosis of Pompe disease in the control group (n = 3); however, newborn screening resulted in an earlier diagnosis of Pompe disease: patients were <1 month old compared with 3 to 6 months old in the control group. CONCLUSIONS. To our knowledge, this is the first large-scale study to show that newborn screening for Pompe disease is feasible. Newborn screening allows for earlier diagnosis of Pompe disease and, thus, for assessment of the value of an earlier start of treatment.

OBJECTIVE: Pompe disease causes progressive, debilitating, and often life-threatening musculoskeletal, respiratory, and cardiac symptoms. Favorable outcomes with early intravenous enzyme-replacement therapy and alglucosidase alfa have been reported, but early clinical diagnosis before the development of severe symptoms has rarely been possible in infants. METHODS: We recently conducted a newborn screening pilot program in Taiwan to improve the early detection of Pompe disease. Six of 206088 newborns screened tested positive and were treated for Pompe disease. Five had the rapidly progressive form of Pompe disease, characterized by cardiac and motor involvement, and were treated soon after diagnosis. The sixth patient was started on treatment at 14 months of age because of progressive muscle weakness. Outcomes were compared with treated patients whose disease was diagnosed clinically and with untreated historical control subjects. RESULTS: At the time of this report, patients had been treated for 14 to 32 months. The 5 infants who had early cardiac involvement demonstrated normalization of cardiac size and muscle pathology with normal physical growth and age-appropriate gains in motor development. The infant without cardiac involvement also achieved normal motor development with treatment. Survival in patients who had newborn screening was significantly improved compared with those in the untreated reference cohort (P = .001). Survival in the treated clinical comparators was reduced but not statistically different from that in the newborn screening group (P = .48). CONCLUSIONS: Results from this study indicate that early treatment can benefit infants with Pompe disease and highlight the advantages of early diagnosis, which can be achieved by newborn screening.

Collapsing response mediator protein-1 (CRMP-1) was initially identified in brain and has been implicated in plexin-dependent neuronal function. The high amino acid sequence identity among the five CRMPs has hindered determination of the functions of each individual CRMP. We generated viable and fertileCRMP-1knock-out (CRMP-1^−/−) mice with no evidence of gross abnormality in the major organs.CRMP-1^−/−mice exhibited intense microtubule-associated protein 2 (MAP2) staining in the proximal portion of the dendrites, but reduced and disorganized MAP2 staining in the distal dendrites of hippocampal CA1 pyramidal cells. Immunoreactivity to GAP-43 (growth-associated protein-43) and PSD95 (postsynaptic density-95) (a postsynaptic membrane adherent cytoskeletal protein) was also decreased in the CA1 region of the knock-out mice. These changes were consistent with the mutant mice showing a reduction in long-term potentiation (LTP) in the CA1 region and impaired performance in hippocampal-dependent spatial learning and memory tests.CRMP-1^−/−mice showed a normal synapsin I labeling pattern in CA1 and normal paired-pulse facilitation. These findings provide the first evidence suggesting that CRMP-1 may be involved in proper neurite outgrowth in the adult hippocampus and that loss of CRMP-1 may affect LTP maintenance and spatial learning and memory.