Specialty neurology ICD-9-CM 330.8 DiseasesDB 29298 | ICD-10 G31.8 OMIM 203700 MeSH D002549 | |
Alpers' disease, also called Alpers' syndrome, Alpers-Huttenlocher syndrome (AHS), progressive sclerosing poliodystrophy, and progressive infantile poliodystrophy, is a progressive degenerative disease of the central nervous system first recognized by Alfons Maria Jakob, a German neuropathologist, that occurs mostly in infants and children. It is an autosomal recessive disorder caused by certain genetic mutations in the POLG gene.
Contents
Presentation
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.
Treatment
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.
Prognosis
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.
Historical examples
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 for his first 18 months; he was crawling and walking, and said his first words at 12 months. But when he was 19 months old, he experienced anorexia, diarrhea, and vomiting, 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, 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.
Research
There is much research being done through the NINDS, where they are looking to find ways to diagnose the disease sooner, prevent the disease from happening in the beginning, eliminate all non-specific symptoms of Alpers’ disease, and find treatments for the disease.
Eponym
It is named after Bernard Jacob Alpers and Peter Huttenlocher.