Alpers' disease

Definition

Alpers' disease is an early-onset, progressive neurological degenerative disease that severely affects the brain and liver. In the familial (inherited) form of the disorder, it is transmitted as a recessive condition, which means that parents are unaffected, but both are carriers. Carrier parents have a 25% risk of having their biological child affected with Alpers' disease.

Description

Alpers' disease was first described by the late neurologist Alfons Maria Jakob (1884–1931). The disease was characterized and published by Bernard Jacob Alpers, Erna Christensen, and Knud Haraldsen Krabbe; thus, Alpers' disease is also known as Christensen's disease or Christensen-Krabbe disease. Additionally, the disease is known as progressive sclerosing poliodystrophy. Alpers' disease afflicts children and is eventually fatal. Degeneration in cognitive processes (reasoning ability) and muscular involvement caused by the disease is unrelenting and relatively rapid. Physically, children with Alpers' disease lose control of their muscle movements. The ramifications of this disorder can significantly affect the emotional state of the person with Alpers' disease, along with family members caring for them.

Demographics

Alpers' disease is a rare disorder. Due to complications related to the diagnosis of Alpers' disease, it is difficult to estimate how often it occurs in the population. Both genders are affected with equal frequency.

Causes and symptoms

Children with Alpers' disease usually develop symptoms between the ages of three months and five years old. Initially, the first symptom early in life is seizures (convulsions). These children tend to be hypotonic (unable to achieve normal muscle tone) and their limbs seem to be stiff. This is usually followed by the failure to reach cognitive and developmental milestones. Mental retardation is progressive in these children.

Among the most devastating features of this disorder is the progressive dementia . In children with Alpers' disease, mental deterioration can occur rapidly. The pathological nature of the defect involves an area of the brain called the cerebrum in which a specific part (the gray matter) is affected. Spastic quadriplegia (inability to use and control movements of the arms and legs) can develop in the later stages of the disorder. Blindness is also observed, and this is usually due to a condition called optic atrophy. In optic atrophy, the optic nerve degenerates, resulting in the inability to process visual information from the eye to the brain.

The liver is also affected. Liver conditions that these children experience are jaundice or complete liver failure in more severe cases. Researchers at the National Institutes of Health (NIH) consider that children with Alpers' disease are often misdiagnosed as having childhood jaundice or liver failure. This is due to the problems associated with making a diagnosis in living patients.

Currently, the specific mechanism, whether genetic, environmental, or both, that causes this disease is unknown. Scientists assume that Alpers'disease is caused by an underlying metabolic defect. Mutations in the DNA of the mitochondria (DNA that is a separate genome from the nucleus) have been associated with this disorder. The mitochondria functions to produce energy to tissues and is particularly important for tissues such as the brain.

Diagnosis

Currently, the only way to arrive at a definitive diagnosis is by autopsy following the death of the child. A postmortem examination of the brain and liver is required.

Treatment team

Because children affected with Alpers' disease usually develop convulsions, they are first directed to a neurologist. An experienced neurologist is always necessary in order to get the appropriate palliative (supportive) care and treatment for these seizures. As the disease progresses, occupational therapists can provide aids for positioning and comfort. Due to the rapid nature of the disorder and the unavailability of treatment to slow the progression, children with Alpers' disease are usually unable to attend school. There are, however, support specialists and organizations that have experience with severe neurological disorders. The National Organization for Rare Disorder can help affected families find local support organizations. There are also organizations such as the Genetic Alliance that help identify support groups to allow families affected by genetic diseases to find other families with the same or related disorders. These organizations can be a tremendous help in alleviating the many emotional and situational burdens that arise by allowing family members to talk to other families that have experience with diseases such as Alpers' disease. Physical therapy can also be helpful to maintain range of motion in the child's arms and legs for as long as possible.

Treatment

There is no cure for Alpers'disease. Also, there is currently no treatment that will slow the progression of the disease. Therefore, treatment is aimed at symptoms such as the seizures. The neurologist must consider the choice of anticonvulsant carefully to avoid ones that may have an adverse effect on the liver.

Recovery and rehabilitation

As Alpers'disease is progressive and eventually fatal, emphasis is placed not upon recovery, but on maintaining functionality as long as possible. Several lifestyle adaptations must be addressed, as children with Alpers' disease eventually require full-time personal care. Depending on how severely and how rapidly the symptoms develop, families may require structural changes such as wheelchair access or other household modifications.

Clinical trials

As of February 2004, there are no ongoing clinical trials designed specifically to treat or study Alpers' diseases.

Prognosis

The prognosis for children with Alpers' disease is poor. Affected individuals typically die within the first decade of life, but in some cases of rapid progression, death can occur in as little as a few months after symptoms become apparent. Seizures can be particularly devastating, as they are often continuous and can lead to death. Other causes of death include complications related to liver disease or cardio-respiratory failure.

Resources

PERIODICALS

Alpers, B. B. "Diffuse Progressive Degeneration of the Gre Matter of the Cerebrum." Archives of Neurology and Psychiatry (1931) 25: 469–505.

Blackwood, W., P. H. Buxton, J. N. Cumings, D. J. Robertson, and S. M. Tucker. "Diffuse Cerebral Degeneration in Infancy (Alpers' Disease)." Archives of Disease in Childhood 38, (1963): 193–204.

Boyd, S. G., A. Harden, J. Egger, and G. Pampiglione. "Progressive Neuronal Degeneration of Childhood with Liver Disease ('Alpers' Disease'): Characteristic Neurophysiological Features." Neuropediatrics 17, no. 2 (1986 May): 75–80.

Christensen, E., and K. H. Krabbe. "Poliodystrophia Cerebri Progressiva (Infantilis): Report of a Case." Archives of Neurology 61 (1949): 28–43.

Fitzgerald, J. F., R. Troncone, and M. A. Del Rosario. "Clinical Quiz. Alpers' Disease." J Pediatr Gastroenterol Nutr. 28, no.5 (May 1999): 501, 509.

Narkewicz, M. R., R. J. Sokol, B. Beckwith, J. Sondheimer, and A. Silverman. "Liver Involvement in Alpers' Disease." J Pediatr. 119, no.2, (Aug 1991): 260–7.

OTHER

National Institutes of Health (NIH). NINDS Alpers' Disease Information Page. February 3, 2004 (March 30, 2004). <http://www.ninds.nih.gov/health_and_medical/disorders/alpersdisease_doc.htm>.

ORGANIZATIONS

Genetic Alliance, Inc. 4301 Connecticut Ave. NW, Suite 404, Washington, DC 20008-2369. (202) 966-5557; Fax: (202) 966-8553. info@geneticalliance.org. <http://www.geneticalliance.org>.

March of Dimes Birth Defects Foundation. 1275 Mamaroneck Avenue, White Plains, NY 10605. (914) 428-7100 or (888) MODIMES; Fax: (914) 428-8203. askus@marchofdimes.com. <http://www.marchofdimes.com>.

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). National Institutes of Health, Bldg. 31, Rm. 9A04, Bethesda, MD 20892-2560. (301) 496-3583. <http://www.niddk.nih.gov>.

National Organization for Rare Disorders (NORD). P.O. Box 1968, 55 Kenosia Avenue, Danbury, CT 06813-1968. (203) 744-0100 or (800) 999-NORD; Fax: (203) 798-2291. orphan@rarediseases.org. <http://www.rarediseases.org>.

Bryan Richard Cobb, PhD