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Hers disease is a genetic metabolic disorder caused by a deficiency of the enzyme, liver phosphorylase. This enzyme is necessary to break down (metabolize) glycogen, a carbohydrate that is stored in the liver and muscle and used for energy. Deficiency of this enzyme results in the abnormal accumulation of glycogen in the body. Hers disease is one of a group of disorders known as the glycogen storage disorders. It is characterized by enlargement of the liver (hepatomegaly), moderately low blood sugar (hypoglycemia), elevated levels of acetone and other ketone bodies in the blood (ketosis), and moderate growth retardation. Symptoms are not always evident during childhood, and children are usually able to lead normal lives.
Although symptoms of Hers disease may not be apparent during childhood, some liver enlargement will be present. Many individuals will have no apparent symptoms (asymptomatic). In general, mild to moderately low blood sugar (hypoglycemia) may be present and can cause symptoms of faintness, weakness, hunger, and nervousness. Diminished muscle tone (hypotonia) and mild muscle weakness may occur in some cases.
Growth rate may be slowed, and enlargement of the liver may occur because of an excess accumulation of glycogen. Glycogen is the stored form of energy derived from carbohydrates. In many cases, the body can adapt to low blood sugar levels and is able to produce energy by other means. Therefore, symptoms may go unnoticed for long periods of time.
Liver enlargement often disappears by puberty and final adult height is often normal. Muscle strength and tone is usually normal by adulthood as well.
Hers disease is inherited as an autosomal recessive trait. The disorder is caused by a lack of the enzyme known as liver phosphorylase. Because of this enzyme deficiency, the stored form of energy derived from carbohydrates (glycogen) may accumulate in the liver.
Genetic diseases are determined by two genes, one received from the father and one from 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%.
Investigators have determined that Hers disease occurs as a result of disruptions or changes (mutations) of the liver glycogen phosphorylase gene (PYGL gene located on the long arm (q) of chromosome 14 (14q21-q22). The PYGL gene encodes for the liver phosphorylase enzyme. Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, with an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further subdivided into many bands that are numbered. For example, "chromosome 14q21-q22" refers to bands 21-22 on the long arm of chromosome 14. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
The incidence of glycogen storage diseases is estimated to be between 1 in 20,000 and 1 in 25,000 persons in the United States. The incidence of Hers disease is unknown, although the disorder has a higher prevalence in the Mennonite population. Symptoms of Hers disease are usually not noticed until adulthood although the disorder may present in childhood.
Symptoms of the following disorders can be similar to those of Hers disease. Comparisons may be useful for a differential diagnosis:
Glycogen storage disease type I (GSDI or von Gierke disease) is characterized by the accumulation of glycogen and fat in the liver and kidneys that can result in enlargement of the liver and kidneys and growth retardation leading to short stature. GSDI is associated with abnormalities in the G6PC gene or SLC37A4 gene that result in enzyme deficiencies that cause excess amounts of glycogen to be stored in the body tissues and low levels of glucose in the blood. Type I glycogen storage disease is inherited as an autosomal recessive genetic disorder. (For more information on this disorder, choose "GSDI" as your search term in the Rare Disease Database.)
Glycogen storage disease type III (GSDIII or Forbes disease) is characterized by excess amounts of an abnormal glycogen (the stored form of energy that comes from carbohydrates) in the liver, muscles and, in some cases, the heart. Symptoms are caused by a lack of the enzyme amylo-1,6 glucosidase (debrancher enzyme) and include growth delays, low blood sugar (hypoglycemia), an elevated level of fatty substances in the blood (hyperlipemia), a protruding abdomen, and an enlarged liver. Forbes disease is inherited as an autosomal recessive trait. (For more information on this disorder, choose "GSDIII" as your search term in the Rare Disease Database.)
Hereditary fructose intolerance (HFI) is an inherited inability to digest fructose (fruit sugar) or its precursors (sugar, sorbitol and brown sugar). This is due to a deficiency of activity of the enzyme fructose-1-phosphate aldolase, resulting in an accumulation of fructose-1-phosphate in the liver, kidney, and small intestine. Fructose is a naturally occurring sugar that is used as a sweetener in many foods, including many baby foods. This disorder can be life-threatening in infants and ranges from mild to severe in older children and adults. People who have HFI usually develop a strong dislike for sweets and fruit. After eating foods containing fructose, they may experience such symptoms as severe abdominal pain, vomiting, and low blood sugar (hypoglycemia). HFI is inherited as an autosomal recessive trait. (For more information on this disorder, choose "HFI" as your search term in the Rare Disease Database.)
A diagnosis of Hers disease is based on a test for activity of the liver phosphorylase enzyme. A small fragment of liver tissue is surgically removed (biopsy) and assayed for the activity of the enzyme. In persons with Hers disease, this enzyme activity will be reduced.
Because symptoms of Hers disease are generally mild, the disorder usually requires no treatment other than avoidance of prolonged fasting and monitoring by a physician. In individuals experiencing fasting hypoglycemia, a high carbohydrate diet and frequent feedings may be recommended.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.
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Dr. Y.T. Chen at Duke University Medical Center, at the request of the Glycogen Storage Disease Association, is collecting DNA from patients with glycogen storage disease type I to form a DNA bank for GSDI. Interested patients may contact the Glycogen Storage Diseases Association for further information. The address and phone number of the organization are listed in the Resources section of this report.
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The Merck Manual 17th ed: M. H. Beers and R. Berkow,: eds; Merck Research Laboratories, 1999. Pp. 2387-89.
Cecil Textbook of Medicine, 20th ed.: J. C. Barnett and F. Plum., Eds.: W.B. Saunders Co., 1996. Pp. 1082-83.
Mutations in the Liver Glycogen Phosphorylase Gene (PYGL) Underlying Glycogenesis Type VI. B. Burwinkel et al., Am J Hum Genet. (Apr 1998, 62 (4)). Pp. 785-91.
Identification of a Mutation in Liver Glycogen Phosphorylase in Glycogen Storage Disease VI. S. Chang et al., (May 1998, 7 (5)). Pp. 865-70.
Effect of Clonidine on the Height of a Child with Glycogen Storage Disease Type TYPE VI: A 13 Year Follow-up Study. T. Asami et al., Acta Paediatr Jpn., Oct 1996, 38 (5)). Pp. 524-28.
Report last updated: 2007/09/23 00:00:00 GMT+0