Pompe disease is a generalized lysosomal glycogenosis affecting essentially
the skeletal muscles and the heart. It is due to the deficiency of acid cy
-glucosidase, also called acid maltase, involved in glycogen degradation by
the cleavage of alpha-1,4 and alpha-1,6 glycosidic linkages. The severe in
fantile, milder juvenile, and late-onset or adult forms are associated unde
r the generic name of glycogenoses type II. The clinical picture can differ
according to these variants, forming a clinical spectrum from cardiorespir
atory failure with early death in the infantile variant to late muscular we
akness or respiratory problems in the adult variant. Enzymatic pre- and pos
tnatal diagnoses and mutation characterization are available. Different the
rapeutic attempts have been conceived and some of them have come to clinica
l trials. Several pilot studies have demonstrated the feasibility of gene t
herapy and remarkable advances have been realized. Of particular interest,
strategies for gene therapy in at generalized disease like Pompe disease mu
st be accompanied by the secretion and uptake of the corrective enzyme by m
ore distant cells or tissues in order to obtain efficient results. Prelimin
ary positive results have been obtained in animal models, and near approach
es with improvements in the access to muscle and heart, in the efficacy and
innocuity of vectors, and in the clinical evolution are proposed. Gene the
rapy is a promising strategy for Pompe disease. However, several steps must
be explored before this method becomes clinically successful. (C) 2000 Aca
demic Press.