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Alpers Disease

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

Copyright 1989, 1996, 1999, 2000, 2006, 2007

Synonyms of Alpers Disease

Disorder Subdivisions

General Discussion

Alpers disease is a progressive neurologic disorder that begins during childhood and is complicated in many instances by serious liver disease. Symptoms include increased muscle tone with exaggerated reflexes (spasticity), seizures, and loss of cognitive ability (dementia).

Symptoms

Alpers disease usually begins during early childhood, usually indicated by seizures at any age between 3 months and 5 years. It is characterized by lack of coordination of motor movement, partial paralysis, seizures, and muscle twitching. The child is unable to achieve normal muscle tone (hypotonia), yet the limbs appear to be stiff. On MRI examination an increased density of the grey matter in the brain is noted. Usually, but not always, Alpers disease is associated with liver damage. Mental retardation may be severe and is progressive. The loss of intellectual functions such as thinking, remembering, and reasoning may also interfere with a person's daily functioning (dementia). In later stages, patients may lose control of the movement of their arms and legs (spastic quadriplegia). The liver may become cirrhotic and fail completely, or may not progress beyond signs of jaundice. Affected individuals may also become blind as a result of optic atrophy as the optic nerve degenerates.

Causes

Many researchers believe that Alpers Syndrome, rather than being a distinct disorder, is a clinical entity (i.e., cerebral gray matter degeneration in association with liver disease) that may be due to a number of different causes. In some cases, it is believed that the syndrome may be inherited as an autosomal recessive genetic trait. In other cases, clinicians attribute the disorder to a prion or prion-like molecule. Some researchers believe that certain individuals may inherit a genetic predisposition for the disorder; in such cases, certain environmental factors in combination with such a genetic predisposition may ultimately result in expression of the disorder. Research has also indicated that certain metabolic defects or mitochondrial abnormalities may play some role in causing the disorder.

Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective 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 of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Affected Populations

It is thought that Alpers disease affects males and females in equal numbers usually during early childhood. However, some clinicians are convinced that the difficulty of diagnosis makes estimating the frequency of this disorder less accurate. It is probable that Alpers disease affects fewer, than one (1) person per 200,000 of population.

Related Disorders

Symptoms of the following disorders can be similar to those of Alpers disease. Comparisons may be useful for a differential diagnosis:

Myoclonic epilepsy is a hereditary neurologic disorder inherited through recessive genes. It is characterized by sudden brief contractions of groups of muscles. Onset is usually between the ages of six and sixteen. During the initial period of seizures there is loss of consciousness. After years of attacks of increasing frequency and severity, spasms involving the muscles of the face, trunk, arms, and legs intensify. Untreated, this type of epilepsy can lead to progressive dementia. (For more information on this disorder, choose "Epilepsy" as your search term in the Rare Disease Database.)

Leigh's disease is a genetic metabolic disorder characterized by lesions of the brain, spinal cord, optic nerve and in some cases, an enlarged heart. The disorder is usually first diagnosed during infancy but may begin later. Symptoms during infancy may include low body weight, slow growth, tremors, skin changes and interrupted breathing patterns. Progressive neurological disturbances, mental retardation, slurred speech and loss of motor coordination (ataxia) may occur. Abnormalities of eye movement and other vision problems may develop in cases with later onset. (For more information on this disorder, choose "Leigh" as your search term in the Rare Disease Database.)

Wernicke encephalopathy is a degenerative brain disorder characterized by a deficiency of thiamine. It is marked by loss of coordination (ataxia) and apathy, confusion, disorientation or delirium. Various vision dysfunctions may also develop. This disorder often occurs in conjunction with Korsakoff syndrome which involves a Vitamin B1 (thiamine) deficiency usually caused by alcoholism. Wernicke encephalopathy can be severely disabling and life threatening if it is not recognized and treated early. (For more information on this disorder, choose "Korsakoff" as your search term in the Rare Disease Database.)

Batten disease is a hereditary lipid storage disorder transmitted as a recessive trait. It is characterized by rapidly progressive vision failure (optic atrophy), deterioration of intellect, seizures, loss of muscular coordination (ataxia) and a backward lateral curvature of the spinal column (kyphoscoliosis). Occurring mostly in white families of Northern European Scandinavian ancestry, Batten Disease usually begins between five and seven years of age. (For more information on this disorder, choose "Batten" as your search term in the Rare Disease Database.)

Tay-Sachs disease is a genetic disorder in children that causes the progressive destruction of the central nervous system. It is generally found among children of eastern European Jewish heritage. Infants with Tay-Sachs disease appear normal at birth and seem to develop normally until the age of about six months. The first signs of the disease vary and become evident at different ages. These signs may include slowed development, loss of peripheral vision, abnormal startle response, progression of feeding difficulties, weakness, restlessness and cherry red spots on the retina. At the age of one year, recurrent convulsions, loss of previously learned skills and muscle coordination, blindness, mental retardation, flaccidity and/or paralysis may occur. This disorder is inherited as a recessive trait. (For more information on this disorder, choose "Tay-Sachs" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Alpers Syndrome is usually diagnosed during infancy based upon a thorough clinical evaluation, a detailed patient history, and a variety of specialized tests. Such tests may include specialized imaging studies of the brain, which may reveal degeneration of the outer portion (cerebral cortex) and, in some cases, other areas of the brain.

Electroencephalography (EEG), which records the brain's electrical impulses, may reveal an overall slowing of the brain's electrical activity and/or other electrical discharge abnormalities characteristic of seizure activity. Only post mortem confirmation is possible by means of a brain biopsy.

Treatment
There is no treatments available that will stop the progress of the disease. However, some of the symptoms can be treated in order to make the patient as comfortable as possible under the circumstances. There are drugs available to treat the frequency of the seizures, to cope with muscle spasms and joint pain, and to treat infection.

Physical therapists may be able to help parents to find more comfortable positions for the child while sitting or standing. Massage often reduces the stress involved. All treatment for Alpers Syndrome is symptomatic and supportive.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources contact:
www.centerwatch.com.

Alpers Disease Resources

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at solivo@rarediseases.org.)

Other Organizations:

References

TEXTBOOKS
Sahoo S, Rosser T, Pearl PL. Alpers Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:511-12.

Lyon G, Adams RD, Kolodny EH. Eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. McGraw-Hill Companies. New York, NY; 1996:81-84.

Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. McGraw-Hill Companies. New York, NY; 2001:2388.

Rowland LP. Ed. Merritt's Neurology. 10th ed. Lippincott Williams & Wilkins. Philadelphia, PA. 2000:584.

JOURNAL ARTICLES
Kollberg G, Moslemi AR, Darin N, Nennesmo I, et al. POLG1 mutations associated with progressive encephalopathy in childhood. J Neuropathol Exp Neurol. 2006;65:758-68.

Tzoulis C, Engelsen BA telstad W, Aasly J, et al. The spectrum of clinical disease caused by A467T and W748S POLG mutations: a study of 26 cases. Brain. 2006. 129(Pt 7):1685-92.

Horvath R, Hudson G, Ferrari G, Futterer N, et al. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain. 2006. 129(Pt7):1674-84.

Nguyen KV, Ostergaard E, Ravn SH, Balslev T, et al. POLG Mutations in Alpers syndrome. Neurology. 2005;58:1493-95.

Naviaux RK, Nguyen KV. POLG mutations associated with Alpers syndrome and mitochondrial DNA depletion. Ann Neurol. 2005;58:491.

Chakraborty C, Nandi S, Jana S. Prion disease: a deadly disease for protein misfolding. Curr Pharm Biotechnol. 2005;6:167-77.

Davidzon G, Mancuso M, Ferraris S, Quinzii C, et al. POLG mutations and Albers syndrome. Ann Neurol. 2005;57:921-23.

Longley MJ, Graziewicz MA, Bienstock RJ, Copeland WC. Consequences of mutations in human DNA polymerase gamma. Gene. 2005;354:125-31.

Hance N, Ekstrand MI, Trifunovic A. Mitochondrial DNA polymerase gamma is essential for mammalian embryogenesis. Hum Mol Genet. 2005;14:1775-83.

Naviaux RK, Nguyen KV. POLG mutations associated with Alpers' syndrome and mitochondrial DNA depletion. Ann Neurol. 2004;55:706-12.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian inheritance in Man (OMIM). The Johns Hopkins University. Alpers Diffuse Degeneration of Cerebral Gray Matter with Hepatic Cirrhosis. Entry Number; 203700: Last Edit Date; 10/15/2005.

NINDS Alpers' Disease Information Page. National Institutes of Health. Last updated January 23, 2006.
www.ninds.nih.gov/disorders/alpersdisease/alpersdisease.htm
Accessed 10/03/2006.

Institute for Child Health. University College London. ©2004. 3pp.
www.ich.ucl.ac.uk/factsheets/families/F040270/index.html
Accessed 10/3/06

Report last updated: 2007/09/23 00:00:00 GMT+0