Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The case of a 17-year-old female with a rare form of type VIII glycogenosis who developed cirrhosis of the liver and hepatocellular tumor is reported. Laparoscopy showed a tumor 50 mm in diameter in the lower portion of the right lobe of the liver. The tumor was biopsied under ultrasonic guidance, and tentatively diagnosed as adenomatous hyperplasia. The patient was also diagnosed as having type VIII glycogenosis (phosphorylase kinase deficiency).
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PMID:A female case of type VIII glycogenosis who developed cirrhosis of the liver and hepatocellular tumor. 255 39

Mutations in three different genes of phosphorylase kinase (Phk) subunits, PHKA2, PHKB and PHKG2, can give rise to glycogen storage disease of the liver. The autosomal-recessive, liver-specific variant of Phk deficiency is caused by mutations in the gene encoding the testis/liver isoform of the catalytic gamma subunit, PHKG2. To facilitate mutation detection and to improve our understanding of the molecular evolution of Phk subunit isoforms, we have determined the structure of the human PHKG2 gene. The gene extends over 9.5 kilonucleotides and is divided into 10 exons; positions of introns are highly conserved between PHKG2 and the gene of the muscle isoform of the gamma subunit, PHKG1. The beginning of intron 2 harbors a highly informative GGT/GT microsatellite repeat, the first polymorphic marker in the PHKG2 gene at human chromosome 16p11.2-p12.1. Employing the gene sequence, we have identified homozygous translation-terminating mutations, 277delC and Arg44ter, in the two published cases of liver Phk deficiency who developed cirrhosis in childhood. As liver Phk deficiency is generally a benign condition and progression to cirrhosis is very rare, this finding suggests that PHKG2 mutations are associated with an increased cirrhosis risk.
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PMID:Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis. 938 16

Phosphorylase kinase-deficient liver glycogenosis manifests in infancy with hepatomegaly, growth retardation, and elevated plasma aminotransferases and lipids. It can be caused by mutations in three different genes of phosphorylase kinase subunits: PHKA2, PHKB, and PHKG2. It is usually a benign condition, often with complete resolution of symptoms during puberty. A minority of patients displays a more severe phenotype with symptomatic fasting hypoglycemia and abnormal liver histology that may progress to cirrhosis. Three patients with liver cirrhosis in childhood analyzed previously all had PHKG2 mutations. This suggested that this genotype may generally cause a more severe clinical manifestation, but to date PHKG2 mutations have been identified in only seven patients. Here, we report mutation analysis in three new patients with liver phosphorylase kinase deficiency and recurrent hypoglycemia, liver fibrosis, and lack of glucagon response but no overt cirrhosis. In all three patients, PHKG2 mutations were found (H89fs[insC], E157K, D215N, W300X). Three of these mutations are novel, bringing the total number of distinct human PHKG2 mutations to 11, found in 10 patients. We conclude that liver phosphorylase kinase deficiency with a severe phenotype, with or without cirrhosis, is indeed often caused by PHKG2 mutations. These patients require active measures to maintain normoglycemia (raw cornstarch, nocturnal tube feeding), which may also alleviate growth retardation and the development of abnormal liver histology.
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PMID:Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene. 1293 Sep 17

Glycogen storage diseases (GSD) are inherited metabolic disorders of glycogen metabolism. Different hormones, including insulin, glucagon, and cortisol regulate the relationship of glycolysis, gluconeogenesis and glycogen synthesis. The overall GSD incidence is estimated 1 case per 20000-43000 live births. There are over 12 types and they are classified based on the enzyme deficiency and the affected tissue. Disorders of glycogen degradation may affect primarily the liver, the muscle, or both. Type Ia involves the liver, kidney and intestine (and Ib also leukocytes), and the clinical manifestations are hepatomegaly, failure to thrive, hypoglycemia, hyperlactatemia, hyperuricemia and hyperlipidemia. Type IIIa involves both the liver and muscle, and IIIb solely the liver. The liver symptoms generally improve with age. Type IV usually presents in the first year of life, with hepatomegaly and growth retardation. The disease in general is progressive to cirrhosis. Type VI and IX are a heterogeneous group of diseases caused by a deficiency of the liver phosphorylase and phosphorylase kinase system. There is no hyperuricemia or hyperlactatemia. Type XI is characterized by hepatic glycogenosis and renal Fanconi syndrome. Type II is a prototype of inborn lysosomal storage diseases and involves many organs but primarily the muscle. Types V and VII involve only the muscle.
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PMID:Glycogen storage diseases: new perspectives. 1755 1

Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to mutations in PHKA1, PHKA2, or PHKB and PHKG2 genes resulting in the deficiency of phosphorylase kinase. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. The majority of cases of GSD IX are attributed to defects in PHKA2 which usually cause a mild disease. We report three patients with PHKG2-related GSD IX presenting with significant hepatic involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping resolved a dilemma about an erroneously normal phosphorylase kinase activity in patient 1. The novel mutation found in all the three patients (p.G220E) affects the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that patients with PHKG2 mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. Therefore, defect in PHKG2 should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis.
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PMID:Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature. 2432 80

Background PHKG2-related liver phosphorylase kinase deficiency is inherited in autosomal recessive pattern and is a rare type of liver glycogenosis. We demonstrated the clinical presentation and genetic determinants involved in children with PHKG2- related liver phosphorylase kinase deficiency. Methodology Ten Pakistani children with liver phosphorylase kinase from seven different families, were enrolled over a period of 18 months. All regions of the PHKG2 gene spanning exons and splicing sites were evaluated through targeted exome sequencing. Variants were analyzed using different bioinformatics tools. Novel variants were reconfirmed by direct sequencing. Results Seven different variants were identified in PHKG2 gene including five novel variants: three stop codons (c.226C>T [p.R76*], c.454C>T [p.R152*] and c.958C>T [p.R320*]), one missense variant c.107C>T (p.S36F) and one splice site variant (c.557-3C>G). All five novel variants were predicted to be damaging by in Silico analysis. The variants are being transmitted through recessive pattern of inheritance except one family (two siblings) has compound heterozygotes. Laboratory data revealed elevated transaminases and triglycerides, normal creatinine phosphokinase and uric acid levels but with glycogen loaded hepatocytes on liver histology. Conclusion PHKG2 related liver phosphorylase kinase deficiency can mimic both liver glycogenosis type I (glucose-6-phosphatase deficiency) & III(amylo-1,6 glucosidase) and characterized by early childhood onset of hepatomegaly, growth restriction, elevated liver enzymes and triglycerides. Molecular analysis would be helpful in accurate diagnosis and proper treatment. The symptoms and biochemical abnormalities in liver glycogenosis due phosphorylase kinase deficiency tend to improve with proper dietary restrictions but need to be monitored for long-term complications such as liver fibrosis and cirrhosis.
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PMID:Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene. 3269 58