Glycogen storage disease IXc is characterized by onset in childhood of hepatomegaly, hypotonia, growth retardation in childhood, and liver dysfunction. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis (Burwinkel ... Glycogen storage disease IXc is characterized by onset in childhood of hepatomegaly, hypotonia, growth retardation in childhood, and liver dysfunction. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis (Burwinkel et al., 1998).
Lerner et al. (1982) described 3 sibs, a boy and 2 girls, with clinical, laboratory, and morphologic findings suggestive of glycogen storage disease IXa. However, the sibs in this study had an increased glycogen content not only in ... Lerner et al. (1982) described 3 sibs, a boy and 2 girls, with clinical, laboratory, and morphologic findings suggestive of glycogen storage disease IXa. However, the sibs in this study had an increased glycogen content not only in the liver but also in muscle, and reduced phosphorylase kinase activity in liver, muscle, erythrocytes, and leukocytes. Lerner et al. (1982) labeled this condition glycogen storage disease IXc. Sovik et al. (1982) reported a Norwegian girl with autosomal recessive GSD9C who was followed-up by Maichele et al. (1996). The parents, who were fourth cousins, and a sister were unaffected. The proband presented at 5 months of age, and again at 3 years, with marked hepatomegaly, marked generalized muscular hypotonia, growth retardation, elevated serum transaminases, and massive liver glycogenosis. PHK activity was barely detectable in liver; in a muscle biopsy, PHK activity was moderately reduced (35% of controls) but muscle glycogen content was nevertheless low. No liver fibrosis was observed. During follow-up, she presented fasting hypoglycemia which gradually subsided. Her growth and development were markedly delayed, but she attained a normal height of 172 cm at age 18. Menarche was at age 17. The relative size of the liver gradually decreased, and at age 18 serum transaminase activities were approaching normal ranges. Serum cholesterol was normal and hypoglycemic symptoms were not noted. Maichele et al. (1996) reported a French girl with the disorder, confirmed by genetic analysis (G189E; 172471.0002). She was hospitalized at 7 months of age because of hypoglycemic episodes and pronounced hepatomegaly. Mild muscle hypotonia and retardation of growth and motor development were also observed. Notable laboratory findings were persistent hypoglycemia with acidosis, and elevated triglycerides and transaminases. Liver histology revealed fine portal fibrosis. Maichele et al. (1996) described a Pakistani girl, whose parents were first cousine, with glycogen storage disease IXc confirmed by genetic analysis (V106E; 172471.0003). The girl was admitted at the age of 15 months for investigation of a distended abdomen due to hepatomegaly with no other clinical symptoms except growth retardation. However, she had increased serum ALT and triglycerides, increased liver glycogen, and severe fibrosis and proliferation of bile ducts on liver biopsy. Beauchamp et al. (2007) reported 2 unrelated Pakistani children with GSD IXc1 confirmed by genetic analysis. Age at diagnosis was about 2 years. Clinical features included hepatomegaly, splenomegaly, short stature in childhood, liver dysfunction, hypoglycemia, lactic acidosis, hyperlipidemia in 1, and fasting ketosis in the other. Muscle weakness and fatigue were also noted. The authors emphasized that molecular analysis results in accurate diagnosis for GSD9 when enzymology is uninformative, and thus allows for proper genetic counseling.
In 3 patients with GSD IXc, born of consanguineous parentage, Maichele et al. (1996) found homozygous PHKG2 mutations (172471.0001-172471.0003). One of the patients had been reported by Sovik et al. (1982).
Burwinkel et al. (1998) identified ... In 3 patients with GSD IXc, born of consanguineous parentage, Maichele et al. (1996) found homozygous PHKG2 mutations (172471.0001-172471.0003). One of the patients had been reported by Sovik et al. (1982). Burwinkel et al. (1998) identified homozygous translation-terminating mutations in the PHKG2 gene, R442X (17241.0004) and 277delC (172471.0005), in 2 patients with liver phosphorylase kinase deficiency who developed cirrhosis in childhood. As liver phosphorylase kinase deficiency is generally a benign condition and progression to cirrhosis is very rare, the findings suggested to the authors that PHKG2 mutations are particularly associated with an increased cirrhosis risk. Burwinkel et al. (2000) reported compound heterozygosity for missense mutations in the PHKG2 gene (172471.0006; 172471.0007) in a child with GSD IXc.