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Archives of Medical Science
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vol. 14
Letter to the Editor

Variable clinical presentation of glycogen storage disease type IV: from severe hepatosplenomegaly to cardiac insufficiency. Some discrepancies in genetic and biochemical abnormalities

Edyta Szymańska, Sylwia Szymańska, Grażyna Truszkowska, Elżbieta Ciara, Maciej Pronicki, Yoon S. Shin, Teodor Podskarbi, Alina Kępka, Mateusz Śpiewak, Rafał Płoski, Zofia T. Bilińska, Dariusz Rokicki

Arch Med Sci 2018; 14, 1: 237–247
Online publish date: 2017/12/19
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Glycogen storage disease (GSD) type IV (Andersen’s disease, amylopectinosis, polyglucosan body disease) is a rare inherited disorder of carbohydrate metabolism. The disease is caused by autosomal recessive mutations in the GBE1 gene (OMIM 607839), which leads to glycogen branching enzyme (GBE) deficiency. This is a critical enzyme in the production of both muscle and liver glycogen. Due to its decreased activity, abnormal long branched molecules of low solubility are formed. These deposits lead to glycogen precipitation in the liver, and subsequently build up in the body tissue, especially the heart and liver. The severity of the disease varies according to the amount of enzyme produced.
In adults, the activity of GBE is higher and symptoms do not appear until later in life [1].
Therefore, clinical manifestations of GSD IV consist of different subtypes with variable ages of onset, severity, and clinical features. The fatal perinatal neuromuscular subtype, which presents in utero with decreased fetal movements, polyhydramnios, and fetal hydrops, and congenital neuromuscular subtype beginning in the newborn period with profound hypotonia, respiratory distress, and dilated cardiomyopathy, both result in death in the neonatal period. The classic progressive hepatic subtype presents with rapidly developing failure to thrive following birth. Clinical manifestations include hepatomegaly, liver dysfunction, and progressive liver cirrhosis, as well as hypotonia, and cardiomyopathy. In this case, death due to liver failure usually occurs by the age of 5 years unless liver transplantation (LTx) is performed. The non-progressive hepatic subtype presents with hepatomegaly, liver dysfunction, myopathy, and hypotonia. However, individuals with this type usually do not show progression of liver disease, and may not even have cardiac, skeletal muscle, or neurologic involvement. The childhood neuromuscular subtype, which is the rarest one, has most variable course. Its onset ranges from the second life decade with a mild disease course to a more severe, progressive course resulting in death in the third decade [2, 3].
The disease diagnosis and management is thus multidisciplinary, and should include specialists in metabolic disorders, hepatology, neurology, and nutrition, as well as in medical or biological genetics.
We report three cases of Polish patients with mutations in the GBE1 gene with various clinical courses of their disease each....

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