|Classification and external resources|
Alpers' disease, also called Alpers' syndrome, progressive sclerosing poliodystrophy, and progressive infantile poliodystrophy, is a progressive degenerative disease of the central nervous system that occurs mostly in infants and children. It is an autosomal recessive disorder meaning two copies of the defective gene is required for active disease, a single copy conveys carrier status. Alpers' disease is caused by certain genetic mutations in the POLG gene.
Alpers' formal name is Alpers-Huttenlocher syndrome (AHS). It was first recognized by Alfons Maria Jakob, a German neuropathologist. First signs of the disease, which include intractable seizures and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. Primary symptoms of the disease are developmental delay, progressive intellectual disability, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. Seizures may include epilepsia partialis continua, a type of seizure that consists of repeated myoclonic (muscle) jerks. Optic atrophy may also occur, often leading to blindness. Deafness may also occur. And, although physical signs of chronic liver dysfunction may not be present, many patients suffer liver impairment leading to liver failure. Alpers' disease is caused by an underlying mitochondrial metabolic defect of POLG,. Pathologically, there is status spongiosus of the cerebral grey matter.
There is no cure for Alpers' disease and, currently, no way to slow its progression. Treatment is symptomatic and supportive. Anticonvulsants may be used to treat the seizures. However, caution should be used when selecting valproate as therapy since it may increase the risk of liver failure. Physical therapy may help to relieve spasticity and maintain or increase muscle tone.
The prognosis for individuals with Alpers' disease is poor. Those with the disease usually are normal at birth and learn to walk and talk but progressively get worse within their first decade of life. Death shortly occurs after and is usually due to liver failure, although cardiorespiratory failure may also occur. Depletion studies cannot be used for early diagnosis because symptoms usually occur months before tissues show the mitochondrial DNA depletion. The first symptoms are usually ones that can relate to several other diseases and disorders so it is difficult to identify Alpers’ syndrome until symptoms are worse and the person is dying.
An infant named B.W. was born with a normal delivery with no complications. His weight was 8 pounds, a normal weight for a newborn baby. Everything was going well his first 18 months; he was crawling, walking, and even said his first words at 12 months. But when he was 19 months old, he experienced anorexia, diarrhea, and vomiting. This was due to lethargy and being hypertonic. He had elevations in liver transaminases and at 30 months developed a seizure disorder. He was unable to talk and lost ability to walk at 38 months. After several more complications, he was in a coma and had end-stage liver disease and died at 42 months. Results later showed eptileptiform discharges first in the left hemisphere and later showed the same in parietal, frontal, and temporal areas of the right hemisphere. There was a complete absence of mitochondrial polymerase activity which led to mtDNA depletion. All of these findings were characteristics of Alpers’ syndrome.
There is much research being done through the NINDS where they are looking to find ways to diagnosis the disease sooner and hopefully find treatments for the disease. They are also looking for ways to prevent the disease from happening in the beginning and eliminating all non-specific symptoms of Alpers’ disease.
- Naudé, J te Water, C M Verity, R G Will, G Devereux, and L Stellitano. (2004.) "Is variant Creutzfeldt-Jakob disease in young children misdiagnosed as Alpers’ syndrome? An analysis of a national surveillance study" Journal of Neurology Neurosurgery and Psychiatry, 2004;75:910-913. (Fee for full text.) Retrieved on 2007-09-27.
- Davidzon, G.; Mancuso, M.; Ferraris, S.; Quinzii, C.; Hirano, M.; Peters, H. L.; Kirby, D.; Thorburn, D. R.; DiMauro, S. : POLG mutations and Alpers syndrome. Ann. Neurol. 57: 921-924, 2005.
- Naviaux, Robert. "Mitochondrial DNA Polymerase y Deficiency and mtDNA Depletion in a Child with Alpers' Syndrome". Wiley Online Library. John Wiley & Sons, Inc. Retrieved 28 January 2015.
- Bernard Jacob Alpers at Who Named It?
- Alpers' disease at Who Named It?
- Easton, John (19 August 2013). "Peter Huttenlocher, pediatric neurologist, 1931-2013". The University of Chicago. Retrieved 1 November 2013.