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Normal Function
The GBE1 gene provides instructions for making the glycogen branching enzyme. This enzyme is involved in the last step of the production of a complex sugar called glycogen, which is a major source of stored energy in the body. Glycogen is made up of many molecules of a simple sugar called glucose; some glucose molecules are linked together in a straight line, while others branch off the main line and form side chains. The glycogen branching enzyme is involved in the formation of these side chains. The branched structure of glycogen makes it more compact for storage and allows it to break down more easily when it is needed for fuel.
Health Conditions Related to Genetic Changes
Adult polyglucosan body disease
At least three mutations in the GBE1 gene have been found to cause adult polyglucosan body disease, a condition that affects the nervous system. These mutations change single protein building blocks (amino acids) in the glycogen branching enzyme. One mutation appears to be more common in affected people with Ashkenazi Jewish ancestry. This mutation replaces the amino acid tyrosine with the amino acid serine at position 329 in the enzyme (written Tyr329Ser or Y329S).
Most mutations that cause adult polyglucosan body disease lead to a shortage (deficiency) of the enzyme. As a result, glycogen has fewer side chains. These abnormal glycogen molecules, called polyglucosan bodies, accumulate within cells and cause damage. Nerve cells (neurons) appear to be particularly vulnerable to the accumulation of polyglucosan bodies in this disorder. Damage to neurons causes reduced sensation, weakness, and other nervous system problems in people with adult polyglucosan body disease.
More About This Health ConditionGlycogen storage disease type IV
Approximately 40 mutations in the GBE1 gene have been found to cause glycogen storage disease type IV (GSD IV). This disorder is characterized by liver and muscle problems that usually begin in infancy and are caused by a buildup of abnormal glycogen. Most of the mutations that cause this condition change single amino acids in the glycogen branching enzyme.
The GBE1 gene mutations that cause GSD IV lead to a severe shortage or complete absence of glycogen branching enzyme. As a result, polyglucosan bodies accumulate in cells, leading to damage and cell death. Polyglucosan bodies build up in cells throughout the body, but liver cells and muscle cells are most severely affected in GSD IV. Glycogen accumulation in the liver interferes with liver functioning, causing an enlarged liver and liver disease. The inability of muscle cells to break down glycogen for energy leads to muscle weakness and wasting.
It is unclear why liver and muscle cells are affected by the accumulation of polyglucosan bodies in GSD IV, while neurons are solely affected in adult polyglucosan body disease (described above).
More About This Health ConditionOther Names for This Gene
- amylo-(1,4 to 1,6) transglucosidase
- amylo-(1,4 to 1,6) transglycosylase
- GBE
- GLGB_HUMAN
- glucan (1,4-alpha-), branching enzyme 1
- glycogen branching enzyme
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
References
- Bruno C, van Diggelen OP, Cassandrini D, Gimpelev M, Giuffre B, Donati MA, Introvini P, Alegria A, Assereto S, Morandi L, Mora M, Tonoli E, Mascelli S, Traverso M, Pasquini E, Bado M, Vilarinho L, van Noort G, Mosca F, DiMauro S, Zara F, Minetti C. Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV). Neurology. 2004 Sep 28;63(6):1053-8. doi: 10.1212/01.wnl.0000138429.11433.0d. Citation on PubMed
- Klein CJ, Boes CJ, Chapin JE, Lynch CD, Campeau NG, Dyck PJ, Dyck PJ. Adult polyglucosan body disease: case description of an expanding genetic and clinical syndrome. Muscle Nerve. 2004 Feb;29(2):323-8. doi: 10.1002/mus.10520. Citation on PubMed
- Lossos A, Meiner Z, Barash V, Soffer D, Schlesinger I, Abramsky O, Argov Z, Shpitzen S, Meiner V. Adult polyglucosan body disease in Ashkenazi Jewish patients carrying the Tyr329Ser mutation in the glycogen-branching enzyme gene. Ann Neurol. 1998 Dec;44(6):867-72. doi: 10.1002/ana.410440604. Citation on PubMed
- Massa R, Bruno C, Martorana A, de Stefano N, van Diggelen OP, Federico A. Adult polyglucosan body disease: proton magnetic resonance spectroscopy of the brain and novel mutation in the GBE1 gene. Muscle Nerve. 2008 Apr;37(4):530-6. doi: 10.1002/mus.20916. Citation on PubMed
- Mochel F, Schiffmann R, Steenweg ME, Akman HO, Wallace M, Sedel F, Laforet P, Levy R, Powers JM, Demeret S, Maisonobe T, Froissart R, Da Nobrega BB, Fogel BL, Natowicz MR, Lubetzki C, Durr A, Brice A, Rosenmann H, Barash V, Kakhlon O, Gomori JM, van der Knaap MS, Lossos A. Adult polyglucosan body disease: Natural History and Key Magnetic Resonance Imaging Findings. Ann Neurol. 2012 Sep;72(3):433-41. doi: 10.1002/ana.23598. Citation on PubMed or Free article on PubMed Central
- Moses SW, Parvari R. The variable presentations of glycogen storage disease type IV: a review of clinical, enzymatic and molecular studies. Curr Mol Med. 2002 Mar;2(2):177-88. doi: 10.2174/1566524024605815. Citation on PubMed
- Nolte KW, Janecke AR, Vorgerd M, Weis J, Schroder JM. Congenital type IV glycogenosis: the spectrum of pleomorphic polyglucosan bodies in muscle, nerve, and spinal cord with two novel mutations in the GBE1 gene. Acta Neuropathol. 2008 Nov;116(5):491-506. doi: 10.1007/s00401-008-0417-8. Epub 2008 Jul 26. Citation on PubMed
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