A new variant of type IV glycogenosis: Deficiency of branching enzyme activity without apparent progressive liver disease

Authors

  • Harry L. Greene M.D.,

    Corresponding author
    1. Vanderbilt University Medical Center School of Medicine, Department of Pediatrics, Division of Gastroenterology/Nutrition, Nashville, Tennessee 37232
    2. Washington University School of Medicine, Department of Biochemistry, St. Louis, Missouri 63110
    3. All Children's Hospital, Department of Gastroenterology, St. Petersburg, Florida 33701
    4. Children's Hospital, Department of Pathology, Pittsburgh, Pennsylvania 15213
    • Department of Pediatrics, Division of Gastroenterology/Nutrition, Vanderbilt University Medical Center, D-4130 MCN, Nashville, Tennessee 37232
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  • Barbara I. Brown,

    1. Vanderbilt University Medical Center School of Medicine, Department of Pediatrics, Division of Gastroenterology/Nutrition, Nashville, Tennessee 37232
    2. Washington University School of Medicine, Department of Biochemistry, St. Louis, Missouri 63110
    3. All Children's Hospital, Department of Gastroenterology, St. Petersburg, Florida 33701
    4. Children's Hospital, Department of Pathology, Pittsburgh, Pennsylvania 15213
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  • Daniel T. McClenathan,

    1. Vanderbilt University Medical Center School of Medicine, Department of Pediatrics, Division of Gastroenterology/Nutrition, Nashville, Tennessee 37232
    2. Washington University School of Medicine, Department of Biochemistry, St. Louis, Missouri 63110
    3. All Children's Hospital, Department of Gastroenterology, St. Petersburg, Florida 33701
    4. Children's Hospital, Department of Pathology, Pittsburgh, Pennsylvania 15213
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  • Rocco M. Agostini Jr.,

    1. Vanderbilt University Medical Center School of Medicine, Department of Pediatrics, Division of Gastroenterology/Nutrition, Nashville, Tennessee 37232
    2. Washington University School of Medicine, Department of Biochemistry, St. Louis, Missouri 63110
    3. All Children's Hospital, Department of Gastroenterology, St. Petersburg, Florida 33701
    4. Children's Hospital, Department of Pathology, Pittsburgh, Pennsylvania 15213
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  • Suzanne R. Taylor

    1. Vanderbilt University Medical Center School of Medicine, Department of Pediatrics, Division of Gastroenterology/Nutrition, Nashville, Tennessee 37232
    2. Washington University School of Medicine, Department of Biochemistry, St. Louis, Missouri 63110
    3. All Children's Hospital, Department of Gastroenterology, St. Petersburg, Florida 33701
    4. Children's Hospital, Department of Pathology, Pittsburgh, Pennsylvania 15213
    Search for more papers by this author

Abstract

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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