Última actualización:
September 23, 2007
Años publicados: 1989, 1996, 1999, 2000, 2006, 2007
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).
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.
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.
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.
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.
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: [email protected]
For information about clinical trials sponsored by private sources contact:
www.centerwatch.com.
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
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report