The natural course of infantile Pompe's disease: 20 original cases compared with 133 cases from the literature.
OBJECTIVE
Infantile Pompe's disease is a lethal cardiac and muscular disorder. Current developments toward enzyme replacement therapy are promising. The aim of our study is to delineate the natural course of the disease to verify endpoints of clinical studies.


METHODS
A total of 20 infantile patients diagnosed by the collaborative Dutch centers and 133 cases reported in literature were included in the study. Information on clinical history, physical examination, and diagnostic parameters was collected.


RESULTS
The course of Pompe's disease is essentially the same in the Dutch and the general patient population. Symptoms start at a median age of 1.6 months in both groups. The median age of death is 7.7 and 6 months, respectively. Five percent of the Dutch patients and 8% of all reported patients survive beyond 1 year of age. Only 2 patients from literature became older than 18 months. A progressive cardiac hypertrophy is characteristic for infantile Pompe's disease. The diastolic thickness of the left ventricular posterior wall and cardiac weight at autopsy increase significantly with age. Motor development is severely delayed and major developmental milestones are generally not achieved. For the Dutch patient group, growth deviates significantly from normal despite start of nasogastric tube feeding. Levels of aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase, creatine kinase, or creatine kinase-myocardial band isoenzyme are typically elevated, although aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase increase significantly with age. The patients have fully deleterious mutations. Acid alpha-glucosidase activity is severely deficient.


CONCLUSIONS
Survival, decrease of the diastolic thickness of the left ventricular posterior wall, and achievement of major motor milestones are valid endpoints for therapeutic studies of infantile Pompe's disease. Mutation analysis and measurement of the alpha-glucosidase activity should be part of the enrollment program.
van den Hout
Hannerieke M P
HM
Divison of Metabolic Diseases and Genetics, Department of Pediatrics, Erasmus Medical Center/Sophia Children's Hospital, Rotterdam, The Netherlands. a.vanderploeg@erasmusmc.nl
Hop
Wim
W
van Diggelen
Otto P
OP
Smeitink
Jan A M
JA
Smit
G Peter A
GP
Poll-The
Bwee-Tien T
BT
Bakker
Henk D
HD
Loonen
M Christa B
MC
de Klerk
Johannis B C
JB
Reuser
Arnold J J
AJ
van der Ploeg
Ans T
AT
D001774:Blood Chemical Analysis; D001921:Brain / Q000473:pathology; D006332:Cardiomegaly / Q000175:diagnosis / Q000209:etiology*; D002657:Child Development; D018450:Disease Progression; D006009:Glycogen Storage Disease Type II / Q000150:complications / Q000401:mortality / Q000503:physiopathology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn / Q000254:growth & development; D007234:Infant, Premature; D009154:Mutation; D009426:Netherlands / Q000453:epidemiology; D016019:Survival Analysis; D000520:alpha-Glucosidases / Q000235:genetics / Q000378:metabolism
D000520:alpha-Glucosidases