Pantothenate Kinase-Associated Neurodegeneration

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 characterised by progressive difficulty with movement and speech. Affected people may also experience loss of intellectual function (dementia) and problems with vision. A particular change called the eye-of-the-tiger sign is characteristically 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. Both types involve a buildup of iron in certain parts of the brain; however, the pattern of signs and symptoms varies. The classic form appears earlier in childhood and progresses more rapidly than the atypical form.

A condition called HARP syndrome (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration) is now considered part of pantothenate kinase-associated neurodegeneration. HARP syndrome is much rarer than classic pantothenate kinase-associated neurodegeneration, but 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 1 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 a protein called pantothenate kinase 2. This protein 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 result in the production of abnormal pantothenate kinase 2 or prevent any protein from being made. A lack of functional pantothenate kinase 2 disrupts the production of coenzyme A and allows potentially harmful compounds (such as iron) to build up in the brain. Researchers are not certain how this defect leads to the signs and symptoms of pantothenate kinase-associated neurodegeneration. Because pantothenate kinase 2 functions in mitochondria (the energy-producing centers inside cells), the features 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 are carriers of one copy of the altered gene but do not show signs and symptoms of the disorder.

What other names do people use for pantothenate kinase-associated neurodegeneration?

• NBIA1
• Neurodegeneration with Brain Iron Accumulation Type 1
• PKAN