We describe a 15-year-old boy and his 19-year-old sister with progressive
dilated cardiomyopathy and mild non-progressive proximal lower limb
myopathy, secondary to the accumulation of
amylopectin-like fibrillar
glycogen, (
polyglucosan) bodies, in heart and skeletal muscle. Evidence of idiopathic
amylopectinosis or polysaccharidosis was demonstrated in heart and skeletal muscle tissue by histology, electron microscopy, biochemical, and genetic analysis. In both siblings the heart muscle stored PAS-positive,
proteinase-k resistant and partly
diastase resistant granulo-filamentous material, simulating
polyglucosan bodies.
Glycogen branching enzyme activity, and
phosphofructokinase enzyme activity, measured in skeletal muscle tissue and explanted heart tissue were all within the normal limits, however
glycogen content was elevated. Furthermore, GBE1, PRKAG2,
desmin, alphabeta-
crystallin, ZASP, myotilin, and LAMP-2 gene sequencing revealed no mutation, excluding e.g.
glycogen storage disease type 4 and
desmin-related myofibrillar
cardiomyopathies. In both patients the diagnosis of an idiopathic polysaccharidosis with progressive
dilated cardiomyopathy was made, requiring
heart transplantation at age 13 and 14, respectively. Both patients belong to an autosomal recessive group of biochemically and genetically unclassified severe vacuolar
glycogen storage disease of the heart and skeletal muscle. Up to now unidentified
glycogen synthesis or
glycogen degradation pathways are supposed to contribute to this idiopathic
glycogen storage disease.