ABSTRACT. Glycogen storage disease type IV due to branching enzyme deficiency was found in an inbred family of Norwegian forest cats, an uncommon breed of domestic cats. Skeletal muscle, heart, and CNS degeneration were clinically apparent and histologically evident in affected cats older than 5 mo of age, but cirrhosis and hepatic failure, hallmarks of the human disorder, were absent. Beginning at or before birth, affected cats accumulated an abnormal glycogen in many tissues that was determined by histochemical, enzymatic, and spectral analysis to be a poorly branched C Y -~,~-D -~~U C~I I .Branching enzyme activity was less than 0.1 of normal in liver and muscle of affected cats and partially deficient (0.17-0.75 of normal) in muscle and leukocytes of the parents of affected cats. These data and pedigree analysis indicate that branching enzyme deficiency is a simple autosomal recessive trait in this family. This is the first reported animal model of human glycogen storage disease type IV. Glycogen storage disease type IV (Andersen disease, amylopectinosis, McKusick catalogue no. 232500) is a rare, inherited disorder of glycogen metabolism in humans caused by deficiency of a-1,4 glucan: a-1,4 glucan 6-glycosyl transferase (EC 2.4.1. 18), the glycogen branching enzyme (1-5). An abnormal glycogen that superficially resembles amylopectin, containing longer chain lengths and fewer branch points than normal glycogen (2, 6, 7), is found in skeletal, smooth, and cardiac muscle, central and peripheral nervous systems, liver, and cells of the reticuloendothelial system (1, 2, 8, 9). Fewer than 50 patients with biochemically confirmed glycogen storage disease type IV have been reported. Most affected children fail to thrive before 1 y of age and die from cirrhosis and the sequelae of hepatic failure between 1 and 4 y of age. Some children exhibit signs of cardiac failure or neuromuscular involvement, with or without signs of hepatic disease (8, 10, 1 I), and a few patients with later onset of signs and longer survival have been reported (10,12,13). Orthotopic liver transplantation has been life-saving in a few patients (14). Biochemical evidence and family pedigrees indicate that type IV glycogen storage disease is inherited as an autosomal recessive trait; heterozygote detection and successful prenatal diagnosis have been reported (12,15,16,17). This report describes the clinical, pathologic, biochemical, and genetic characteristics of glycogen storage disease type IV in a family of purebred domestic cats.
MATERIALS AND METHODS
Animals.Affected cats and their family members were clientowned animals. Unrelated control cats were chosen from colonies maintained by the University of Pennsylvania Unit of Laboratory Animal Resources. All animal-use protocols were approved by the Institutional Animal Care and Use Committee of the University and conformed to National Institutes of Health guidelines.Histopathology and electron microscopy. Tissues for light microscopy were fixed in 1.25 M neutral buffered formaldehyde (10% forma...
