Newborn screening for Pompe disease

Pompe disease is an autosomal recessive lysosomal storage disorder caused by  deficiency of acid α-glucosidase (GAA) activity, which results in progressive, debilitating, and often life-threatening symptoms, involving musculoskeletal, respiratory, and cardiac systems. Treatment by enzyme replacement therapy (ERT) with alglucosidase alfa was approved for human use in 2006. In classical IOPD, ERT significantly increases survival rate and improves motor development and cardiac function.

Newborn screening aims to diagnose and treat newborns in early stage by a variety technology.

In newborn screening center at National Taiwan University Hospital, a pilot Pompe newborn screening program has been practiced from 2005 to 2008, testing Pompe disease for approximately 45% of newborns in Taiwan. This is the first large-scale Pompe newborn screening in the world. The screening involved measuring GAA activity in dried blood spot (DBS). After this study, all newborns in Taiwan received GAA screening on voluntary basis.

After screening over 470,000 newborns, we revised the incidence of all types of Pompe disease found by newborn screening to approximately 1 in 17000. Nine newborns (~1 in50 000 newborns)

showed hypertrophic cardiomyopathy during the neonatal period and were classified as having infantile-onset Pompe disease (IOPD). The treatment was given right after diagnosis. All the IOPD patients demonstrated normalization of cardiac size and muscle pathology with normal physical growth and gained age-appropriate motor development. They all lived well without ventilator. Therefore the survival rate and quality of life in newborn screening patients were significantly improved, comparing to the untreated or to the late-treated reference cohort. 
  Our group demonstrates the feasibility of Pompe newbornscreening, and we show that earlytreatment can benefit infants with Pompe disease, highlighting the advantages of early diagnosis, which can be achieved by newborn screening. Through newborn screening, we also are able to detect and close monitor patients with later-onset type, so ERT can be given once they show some physical abnormalities.
pompe disease
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Related publications

Chiang SC, Hwu WL, Lee NC, Hsu LW, Chien YH.*. Algorithm for Pompe disease newborn screening: Results from the Taiwan screening program. Mol Genet Metab. 2012;106 (3): 281-6.

Chien YH, Lee NC, Huang PH, Lee WT, Thurberg BL, Hwu WL. Early pathologic changes and responses to treatment in patients with later-onset Pompe disease. Pediatr Neurol. 2012 Mar;46(3):168-71.

Chen CA, Chien YH, Hwu WL, Lee NC, Wang JK, Chen LR, Lu CW, Lin MT, Chiu SN, Chiu HH, Wu MH. Left ventricular geometry, global function, and dyssynchrony in infants and children with pompe cardiomyopathy undergoing enzyme replacement therapy. J Card Fail. 2011 Nov;17(11):930-6.

 

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Yang CC, Chien YH, Lee NC, Chiang SC, Lin SP, Kuo YT, Chen SS, Jong YJ, Hwu WL. Rapid progressive course of later-onset Pompe disease in Chinese patients. Mol Genet Metab. 2011 Nov;104(3):284-8.

Raben N, Ralston E, Chien YH, Baum R, Schreiner C, Hwu WL, Zaal KJ, Plotz PH. Differences in the predominance of lysosomal and autophagic pathologies between infants and adults with Pompe disease: implications for therapy. Mol Genet Metab. 2010 Dec;101(4):324-31.

Labrousse P, Chien YH, Pomponio RJ, Keutzer J, Lee NC, Akmaev VR, Scholl T, Hwu WL. Genetic heterozygosity and pseudodeficiency in the Pompe disease newborn screening pilot program. Mol Genet Metab. 2010 Apr;99(4):379-83.

Chen LR, Chen CA, Chiu SN, Chien YH, Lee NC, Lin MT, Hwu WL, Wang JK, Wu MH. Reversal of cardiac dysfunction after enzyme replacement in patients with infantile-onset Pompe disease. J Pediatr. 2009 Aug;155(2):271-5.e2.

Ralston E, Swaim B, Czapiga M, Hwu WL, Chien YH, Pittis MG, Bembi B, Schwartz O, Plotz P, Raben N. Detection and imaging of non-contractile inclusions and sarcomeric anomalies in skeletal muscle by second harmonic generation combined with two-photon excited fluorescence. J Struct Biol. 2008 Jun;162(3):500-8.

Chien YH, Lee NC, Peng SF, Hwu WL. Brain development in infantile-onset Pompe disease treated by enzyme replacement therapy. Pediatr Res. 2006 Sep;60(3):349-52.

Kishnani PS, Corzo D, Nicolino M, Byrne B, Mandel H, Hwu WL, Leslie N, Levine J, Spencer C, McDonald M, Li J, Dumontier J, Halberthal M, Chien YH, Hopkin R, Vijayaraghavan S, Gruskin D, Bartholomew D, van der Ploeg A, Clancy JP, Parini R, Morin G, Beck M, De la Gastine GS, Jokic M, Thurberg B, Richards S, Bali D, Davison M, Worden MA, Chen YT, Wraith JE. Recombinant human acid [alpha]-glucosidase: major clinical benefits in infantile-onset Pompe disease. Neurology. 2007 Jan 9;68(2):99-109.

Chien YH, Lee NC, Huang HJ, Thurberg BL, Tsai FJ, Hwu WL. Later-onset Pompe disease: early detection and early treatment initiation enabled by newborn screening. J Pediatr. 2011 Jun;158(6):1023-1027.e1. Epub 2011 Jan 13.

Chien YH, Lee NC, Thurberg BL, Chiang SC, Zhang XK, Keutzer J, Huang AC, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL. Pompe disease in infants: improving the prognosis by newborn screening and early treatment. Pediatrics. 2009 Dec;124(6):e1116-2.

Chien YH, Chiang SC, Zhang XK, Keutzer J, Lee NC, Huang AC, Chen CA, Wu MH, Huang PH, Tsai FJ, Chen YT, Hwu WL. Early detection of Pompe disease by newborn screening is feasible: results from the Taiwan screening program. Pediatrics. 2008 Jul;122(1):e39-45.

Kishnani PS, Hwu WL, Mandel H, Nicolino M, Yong F, Corzo D; Infantile-Onset Pompe Disease Natural History Study Group. A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr. 2006 May;148(5):671-676.

Ko TM, Hwu WL, Lin YW, Tseng LH, Hwa HL, Wang TR, Chuang SM. Molecular genetic study of Pompe disease in Chinese patients in Taiwan. Hum Mutat. 1999;13(5):380-4.