Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.1.18 (branching enzyme)
 628 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type IV glycogenosis is due to branching enzyme deficiency and is usually manifested clinically by progressive liver disease with cirrhosis and hepatic failure between the second and fourth years of life. We describe a 5-year-old boy who, following an acute febrile illness at 2 years of age, was first noted to have hepatomegaly with mildly elevated serum transaminase levels. Liver biopsy revealed hepatic fibrosis with periodic-acid Schiff-positive, diastase-resistant inclusions in hepatocytes and fibrillar inclusions characteristic of amylopectin by electron microscopy. Enzymatic assay revealed deficient hepatic branching enzyme activity with normal activity of glucose-6-phosphatase, debranching enzyme and phosphorylase activities. During the succeeding 3 years, he grew and developed normally with apparent resolution of any clinical evidence of liver disease and only intermittent elevation in serum transaminase levels associated with fever and prolonged fasting. Repeat liver biopsy at 4 years of age showed persistence of scattered hepatocellular periodic-acid Schiff-positive, diastase-resistant inclusions, but no progression of hepatic fibrosis in spite of persistent deficiency of hepatic branching enzyme activity. Skeletal muscle and skin fibroblasts from the patient also showed deficient enzyme activity. Skin fibroblasts from both parents exhibited half the normal control activity, suggesting a heterozygote state. This is the first documented patient with deficiency of branching enzyme but without evidence of progressive hepatic disease. This patient, coupled with reports of other patients with late onset hepatic or muscle disease with branching enzyme deficiency, suggests that the defect resulting in Type IV glycogen storage disease is more heterogenous and possibly more common than previously suspected.
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PMID:A new variant of type IV glycogenosis: deficiency of branching enzyme activity without apparent progressive liver disease. 316 25

Glycogen storage disease type IV (GSD-IV) is an autosomal recessive genetic disorder due to a deficiency in the activity of the glycogen branching enzyme (GBE). A deficiency in GBE activity results in the accumulation of glycogen with fewer branching points and long, unbranched outer chains. The disorder results in a variable phenotype, including musculoskeletal, cardiac, neurological, and hepatic involvement, alone or in continuum, which can be identified at any stage of life. The classic form of GSD-IV is a hepatic presentation, which presents in the first 18 months of life with failure to thrive, hepatomegaly, and cirrhosis that progresses to liver failure, resulting in death by age 5 years. A severe congenital musculoskeletal phenotype with death in the neonatal period has also been described. We report an unusual case of congenital musculoskeletal presentation of GSD-IV with stable congenital hypotonia, gross motor delay, and severe fibro-fatty replacement of the musculature, but no hepatic or cardiac involvement. Molecular analysis revealed two novel missense mutations with amino acid changes in the GBE gene (Q236H and R262C), which may account for the mild phenotype.
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PMID:Non-lethal congenital hypotonia due to glycogen storage disease type IV. 1652 37