Pompe disease is a severe form of muscular dystrophy due to glycogen accumulation in all tissues, especially striated muscle. Disease severity is directly related to the deficiency of acid ␣-glucosidase (GAA), which degrades glycogen in the lysosome. Respiratory dysfunction is a hallmark of the disease, muscle weakness has been viewed as the underlying cause, and the possibility of an associated neural contribution has not been evaluated previously. Therefore, we examined behavioral and neurophysiological aspects of breathing in 2 animal models of Pompe disease-the Gaa ؊/؊ mouse and a transgenic line (MTP) expressing GAA only in skeletal muscle, as well as a detailed analysis of the CNS in a Pompe disease patient. Glycogen content was elevated in the Gaa ؊/؊ mouse cervical spinal cord. Retrograde labeling of phrenic motoneurons showed significantly greater soma size in Gaa ؊/؊ mice vs. isogenic controls, and glycogen was observed in Gaa ؊/؊ phrenic motoneurons. Ventilation, assessed via plethysmography, was attenuated during quiet breathing and hypercapnic challenge in Gaa ؊/؊ mice (6 to >21 months of age) vs. controls. We confirmed that MTP mice had normal diaphragmatic contractile properties; however, MTP mice had ventilation similar to the Gaa ؊/؊ mice during quiet breathing. Neurophysiological recordings indicated that efferent phrenic nerve inspiratory burst amplitudes were substantially lower in Gaa ؊/؊ and MTP mice vs. controls. In human samples, we demonstrated similar pathology in the cervical spinal cord and greater accumulation of glycogen in spinal cord compared with brain. We conclude that neural output to the diaphragm is deficient in Gaa ؊/؊ mice, and therapies targeting muscle alone may be ineffective in Pompe disease.glycogenosis ͉ motor neuron ͉ muscular dystrophy ͉ myopathy

(Circulation 1989;79:549-556) E xperimental studies in animals demonstrate that neutrophils play important roles in the pathophysiology of myocardial ischemia and infarction.1-5 Several epidemiologic studies in human subjects also indicate the relevance of leukocytes in ischemic heart disease. Elevation of leukocyte count in peripheral blood is associated with increased risk of acute myocardial infarction,6-10 its recurrence,1 and the incidence of ventricular fibrillation in the postinfarction period.12 Leukocyte count has also been shown to correlate with the extent of coronary artery disease observed at coronary angiography.13

We report the case of a hepatic undifferentiated (embryonal) sarcoma (UES) arising within a mesenchymal hamartoma (MH) in a 15-year-old girl. Mapping of the tumor demonstrated a typical MH transforming gradually into a UES composed of anaplastic stromal cells. When evaluated by flow cytometry, the MH was diploid and the UES showed a prominent aneuploid peak. Karyotypic analysis of the UES showed structural alterations of chromosome 19, which have been implicated as a potential genetic marker of MH. The histogenesis of MH and UES is still debated, and reports of a relationship between them, although suggested on the basis of histomorphologic similarities, have never been convincing. The histologic, flow cytometric, and cytogenetic evidence reported herein suggests a link between these two hepatic tumors of the pediatric population.