Adult polyglucosan body disease (APBD) is a rare, chronically progressive, metabolic disorder with severe neurological expression. It is caused by the abnormal accumulation of microscopic material (polyglucosan bodies), predominantly within the myelinated nerve fibers (motor neurons). The polyglucosan bodies are spherical and composed of large, complex, sugar-based molecules (branched polysaccharides).
The disorder typically affects both upper and lower motor neurons, resulting from nerve damage within the brain and spinal cord (central nervous system) respectively. Symptoms usually begin during middle age or later and usually include muscle weakness, loss of sensation, and/or wasting of muscles (atrophy) in the arms and/or legs. Impaired bladder control (neurogenic bladder) and/or mental confusion (dementia) also occur.
Adult polyglucosan body disease typically affects both upper and lower motor neurons, resulting in nerve damage within the brain and/or spinal cord (central nervous system). Symptoms usually appear in middle age or later and are progressive. Muscle weakness, loss of sensation, and/or wasting of muscles (atrophy) in the arms and/or legs are characteristic of this disorder. People with APBD may also have impaired bladder control (neurogenic bladder) and/or mental confusion (dementia) of varying degrees.
Progressive gait or walking problems as a result of muscle weakness and spasms (spasticity) are primary symptoms. Short, rhythmic, contractions of various muscles that may be evident through the skin and suggest short, electrical discharges of the nerves involved.
Symptoms vary depending on the area of the nervous system affected by the disorder.
Symptoms of adult polyglucosan body disease are the result of the presence of microscopic particles (polyglucosan bodies) in skeletal muscle nerve cells. Polyglucosan bodies may accumulate in nerve cells in the brain and spinal cord (central nervous system) as well as in peripheral nerves and the lung, heart, liver, and/or kidneys. Tissue reduction (atrophy), tissue loss (necrosis), and/or loss of the fatty sheath surrounding nerve fibers (demyelination) may occur. The mechanism by which the polyglucosan bodies cause nerve damage is not clear.
Adult polyglucosan body disease is inherited as an autosomal recessive trait.
Genetic diseases are determined by the combination of genes for a particular trait which are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Because there is a distinct subset of patients with APBD who also have glycogen storage disease IV (Andersen disease or GSD IV), some clinicians have suggested that the same inherited defect in the metabolism of carbohydrates (branching enzyme dysfunction) responsible for GSD IV may also be the cause of APBD in some cases.
APBD is a very rare disorder that appears to affect males and females in about equal proportions. Familial clustering is observed in about 30% of cases especially among Ashkenazi Jewish populations. About 50 ± cases have been reported in the medical literature.
The group of Ashkenazi Jews who have contracted this disorder all show a specific mutation on the glycogen-branching enzyme gene. This same gene is responsible for the metabolic disorder known as glycogen storage disease IV (GSD-IV) or Andersen disease. Based on this observation, some clinicians believe that APBD is the adult form of GSD-IV which is a metabolic disorder of early childhood. There remains some controversy about this idea.
While a neurologist’s thorough examination is essential to focusing diagnostic attention on APBD, it is through the direct examination of tissue by a pathologist (electron and light microscopy) that a definitive diagnosis is made. The examination of skin, muscle and/or nerve samples (biopsy) reveals the presence of certain particles called polyglucosan bodies. These bodies may also be present in other disorders and may occur in the normal course of aging. However, in cases of APBD the polyglucosan bodies are mostly and almost uniquely in the fibers extending from nerve cells (axons) as opposed to the body of the cells. The presence of the spheroid, polyglucosan bodies in the fibers is key to the diagnosis. Magnetic resonance imaging (MRI) may show abnormalities in the conduction tissue (white matter) of the brain.
Treatment of adult polyglucosan body disease generally requires a team approach and may include physicians, physical therapists, medical social workers, and nurses. Devices that help affected people continue daily activities, such as braces, hand splints, limb supports, or wheelchairs, are important. Affected individuals who are restricted to bed may be made more comfortable with adjustable beds, water mattresses, and/or sheepskin mattress pads.
Genetic counseling may be of benefit for people with adult polyglucosan body disease and their families.
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Klein CM. Adult Polyglucosan Body Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:580-81.
Adams RD, Victor M, Ropper AA. Eds. Principles of Neurology. 6th ed. McGraw-Hill Companies. New York, NY; 1997:967, 1067.
Lyon G, Adams RD, Kolodny EH. Eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. McGraw-Hill Companies. New York, NY; 1996:196.
Trivedi JR, Wolfe GI, Nations SP, et al. Adult polyglucosan body disease associated with Lewy bodies and tremor. Arch Neurol. 2003;60:764-66.
Leel-Ossy L. New data on the ultrstructure of the corpus amylaceum (polyglucosan body). Pathol Oncol Res. 2001;7:145-50
Berkhoff M, Weis J, Schroth G, et al. Extensive white-matterchanges in a case of adult polyglucosan body disease. Neuroradiology. 2001;43:234-36.
Milde P, Guccion JG, Kelly J, et al. Adult polyglucosan body disease. Arch Pathol Lab Med. 2001;125:519-22.
Cavanagh JB. Corpora-amylacea and the family of polyglucosan diseases. Brain Res Brain Res Rev. 1999;29:265-95.
Lossos A, Meiner Z, Barash V, et al. Adult polyglucosan body disease in Ashknazi Jewish patients carrying the Tyr329Ser mutation in the glycogen- branching enzyme gene. Ann Neurol. 1998;44:867-72.
FROM THE INTERNET
Adult polyglucosan body disease. The Doctor’s Doctor. Last Updated: 4/4/2001. 4pp.
McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Polyglucosan Body Disease, Adult Form; APBD. Entry Number; 263570: Last Edit Date; 4/8/1994.
Polyglucosan body disease. Department of Neurology, Washington University School of Medicine. nd. np.
Branching enzyme deficiency. Department of Neurology, Washington University School of Medicine. nd. np.
Excerpt from Glycogen Storage Disease Type IV. EMedicine. nd. 2pp.