Pompe disease in infants: improving the prognosis by newborn screening and early 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.
Chien
Yin-Hsiu
YH
Department of Pediatrics and Medical Genetics, National Taiwan University Hospital, Taipei 10041, Taiwan.
Lee
Ni-Chung
NC
Thurberg
Beth L
BL
Chiang
Shu-Chuan
SC
Zhang
Xiaokui Kate
XK
Keutzer
Joan
J
Huang
Ai-Chu
AC
Wu
Mei-Hwan
MH
Huang
Pei-Hsin
PH
Tsai
Fuu-Jen
FJ
Chen
Yuan-Tsong
YT
Hwu
Wuh-Liang
WL
D009202:Cardiomyopathies / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D003131:Combined Modality Therapy; D018450:Disease Progression; D005500:Follow-Up Studies; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis* / Q000401:mortality / Q000628:therapy; D006801:Humans; D007231:Infant, Newborn; D007262:Infusions, Intravenous; D015997:Neonatal Screening; D010289:Parenteral Nutrition, Total; D026741:Physical Therapy Modalities; D012121:Respiration, Artificial; D015996:Survival Rate; D013624:Taiwan; D000520:alpha-Glucosidases / Q000008:administration & dosage*
C509951:GAA protein, human; D000520:alpha-Glucosidases