Pantothenate Kinase-Associated Neurodegeneration

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What is pantothenate kinase-associated neurodegeneration?

Pantothenate kinase-associated neurodegeneration (formerly called Hallervorden-Spatz syndrome) is a disorder of the nervous system. This condition is characterized by progressive difficulty with movement, typically beginning in childhood. Movement abnormalities include involuntary muscle spasms, rigidity, and trouble with walking that worsens over time. Many people with this condition also develop problems with speech (dysarthria), and some develop vision loss. Additionally, affected individuals may experience a loss of intellectual function (dementia) and psychiatric symptoms such as behavioral problems, personality changes, and depression.

Pantothenate kinase-associated neurodegeneration is characterized by an abnormal buildup of iron in certain areas of the brain. A particular change called the eye-of-the-tiger sign, which indicates an accumulation of iron, is typically seen on magnetic resonance imaging (MRI) scans of the brain in people with this disorder.

Researchers have described classic and atypical forms of pantothenate kinase-associated neurodegeneration. The classic form usually appears in early childhood, causing severe problems with movement that worsen rapidly. Features of the atypical form appear later in childhood or adolescence and progress more slowly. Signs and symptoms vary, but the atypical form is more likely than the classic form to involve speech defects and psychiatric problems.

A condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration), which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration. Although HARP is much rarer than classic pantothenate kinase-associated neurodegeneration, both conditions involve problems with movement, dementia, and vision abnormalities.

How common is pantothenate kinase-associated neurodegeneration?

The precise incidence of this condition is unknown. It is estimated to affect 1 to 3 per million people worldwide.

What genes are related to pantothenate kinase-associated neurodegeneration?

Mutations in the PANK2 gene cause pantothenate kinase-associated neurodegeneration.

The PANK2 gene provides instructions for making an enzyme called pantothenate kinase 2. This enzyme is active in mitochondria, the energy-producing centers within cells, where it plays a critical role in the formation of a molecule called coenzyme A. Found in all living cells, coenzyme A is essential for the body's production of energy from carbohydrates, fats, and some protein building blocks (amino acids).

Mutations in the PANK2 gene likely result in the production of an abnormal version of pantothenate kinase 2 or prevent cells from making any of this enzyme. A lack of functional pantothenate kinase 2 disrupts the production of coenzyme A and allows potentially harmful compounds to build up in the brain. This buildup leads to swelling and tissue damage, and allows iron to accumulate abnormally in certain parts of the brain. Researchers have not determined how these changes result in the specific features of pantothenate kinase-associated neurodegeneration. Because pantothenate kinase 2 functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.

How do people inherit pantothenate kinase-associated neurodegeneration?

This condition is inherited in an autosomal recessive pattern, which means two copies of the gene in each cell are altered. Most often, the parents of an individual with an autosomal recessive disorder each carry one copy of the altered gene but do not show signs and symptoms of the disorder.

Source: National Institutes of Health

Research from K. Freeman and co-authors provides new data about neurodegenerative disease

"Investigations of cognitive functioning have utilized specific neuropsychological tests, without attention to general intellectual skills or adaptive behaviour. Sixteen individuals with PKAN completed measures of global intellectual functioning, and participants or care providers completed measures of adaptive behaviour skills and day-to-day functional limitations. Clinicians provided global ratings of condition severity. Results Testing with standardized measures documented varied phenotypic expression, with general cognitive skills and adaptive behaviour ranging from high average to well below average. Age of disease onset correlated with measures of intellectual functioning, adaptive functioning and disease severity. Findings support previously described clinical impressions of varied cognitive impairment and the association between age of onset and impairment," wrote K. Freeman and colleagues.

The researchers concluded: "Further, they add important information regarding the natural history of the disease and suggest assessment strategies for use in treatment trials."

Freeman and colleagues published the results of their research in the Journal of Intellectual Disability Research (Research from K. Freeman and co-authors provides new data about neurodegenerative disease. Journal of Intellectual Disability Research, 2007;51(Part 6):417-426).

For additional information, contact K. Freeman, 707 SW Gaines, Portland, OR 97239, USA.

The publisher of the Journal of Intellectual Disability Research can be contacted at: Blackwell Publishing, 9600 Garsington Rd., Oxford OX4 2DQ, Oxon, England.

Keywords: United States, Portland, Neurodegenerative Disease, Brain Iron Accumulation, Cognitive Functioning, Functional Skills, Mental Health, Neurodegenerative, Pantothenate Kinase-associated Neurodegeneration.

This article was prepared by Pain & Central Nervous System Week editors from staff and other reports. Copyright 2007, Pain & Central Nervous System Week via NewsRx.com.