Mizuta et al. (1984) and Eishi et al. (1985) described a seemingly unique case of glycogenosis, apparently confined to the heart, with deficient activity of cardiac phosphorylase kinase. The patient, a Japanese male, was found in the neonatal ... Mizuta et al. (1984) and Eishi et al. (1985) described a seemingly unique case of glycogenosis, apparently confined to the heart, with deficient activity of cardiac phosphorylase kinase. The patient, a Japanese male, was found in the neonatal period to have hypoglycemia and general cyanosis; he died of heart failure at the age of 5 months. An apparently identical case was described by Servidei et al. (1988). Servidei et al. (1988) suggested that this disorder is a third variety of phosphorylase kinase deficiency, inherited as an autosomal recessive, that affects muscle alone; symptoms consist of exercise intolerance with myalgia and cramps, and probably with myoglobinuria in some. An X-linked form of phosphorylase kinase deficiency (306000) is characterized by hepatomegaly and a tendency to develop hypoglycemia with fasting; muscle is not affected, but the enzyme defect is expressed in erythrocytes. In an autosomal recessive form of the disorder (261750), both liver and muscle are affected; there is hepatomegaly, stunted growth, and, in some patients, hypotonia and mild weakness. Elleder et al. (1993) reported the case of a male infant who was noted to have heart murmur, mild cardiomegaly, and failure to thrive at the age of 3 weeks and was found to have severe glycogenosis restricted to heart muscle. Rapidly progressive hypertrophic cardiomyopathy caused death at the age of 47 days. Burwinkel et al. (2005) described 5 sporadic, unrelated patients with fatal congenital nonlysosomal cardiac glycogenosis and noted the similarities between these patients and those previously described with so-called phosphorylase kinase deficiency of the heart. All but 1 had extreme cardiomegaly, onset of cardiac or respiratory distress in the neonatal period, and death at 3 weeks to 5 months of age. Burwinkel et al. (2005) also observed low to absent phosphorylase kinase enzyme activity in their patients' heart autopsy specimens, but sequence analysis in 4 of their patients revealed no mutations in the 8 genes encoding phosphorylase kinase subunits or in the 2 genes encoding the muscle and brain forms of glycogen phosphorylase. Burwinkel et al. (2005) suggested that the low phosphorylase kinase activity in autopsy specimens from their patients and perhaps in the previously reported cases is likely to be secondary or artifactual in nature.
In 3 of 5 patients with fatal congenital nonlysosomal cardiac glycogenosis, Burwinkel et al. (2005) identified heterozygosity for an R531Q mutation in the PRKAG2 gene (602743.0007). Burwinkel et al. (2005) noted that this severe phenotype characterized by fetal ... In 3 of 5 patients with fatal congenital nonlysosomal cardiac glycogenosis, Burwinkel et al. (2005) identified heterozygosity for an R531Q mutation in the PRKAG2 gene (602743.0007). Burwinkel et al. (2005) noted that this severe phenotype characterized by fetal onset, extreme cardiomegaly, and death in infancy extended the clinical spectrum of PRKAG2 mutations, which had previously been shown to cause familial hypertrophic cardiomyopathy with Wolff-Parkinson-White syndrome (600858). Patients with the R531Q mutation died of hemodynamic and respiratory failure secondary to hypertrophic nonobstructive cardiomyopathy, but also had Wolff-Parkinson-White-like conduction anomalies.