G.P.121 - A novel neuromuscular form of glycogen storage disease type IV characterized by spinal stiffness, arthrogrypotic features, and rare polyglucosan bodies in muscle biopsy

Abstract

Glycogen storage disease type 4 (GSD-IV) is an autosomal recessive disorder characterized by the deposition of an amylopectin-like polysaccharide called polyglucosan in all tissues, associated with mutations in the gene encoding for the glycogen branching enzyme (GBE1). The clinical spectrum is wide ranging from isolated non-progressive hepathopathy, neuromuscular disorders with variable age of onset, to the adult polyglucosan body disease (APBD). Two infantile neuromuscular presentations consisting of fetal akinesia deformation sequence, or hypotonia, muscle wasting, and fatal neuronal involvement with cardiomyopathy have been described. Here we report on a 3-year-old boy, born from healthy consanguineous Turkish parents, presenting with neonatal hypotonia, poor sucking, and arthrogrypotic features (neck pterygium, adducted thumbs). He presented motor delay, important neck and periscapular muscle wasting, hip flexion contractures, hyperlordosis, and rigid spine. Brain MRI was normal and muscle MRI revealed thin neck muscular bulk, and alteration of trapezius, sternocleidomastoid, pectoral and erector spine muscles. A muscle biopsy performed at 3 years revealed the presence of only two muscle fibers harboring small PAS positive inclusions that remained undigested after alpha-amylase treatment. Electron microscopy confirmed the presence of storage material composed by filamentous structures. GBE1 gene sequencing revealed two pathogenic heterozygous variants (c.708G>C and c.2052+1G>A). With our report we describe a phenotype never of GSD type 4. The identification of polyglucosan bodies in muscle by light and electron microscopy was pivotal in orientating the molecular diagnosis toward GBE1 gene.