What is the definition of 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) syndrome, which was historically described as a separate syndrome, is now considered part of pantothenate kinase-associated neurodegeneration.

What are the causes for 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 prevalent 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.

Is Pantothenate Kinase-Associated Neurodegeneration an inherited disorder?

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

  • Journal: Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova
  • Published —
Case-report of neuroacanthocytosis associated with a compound mutation in the VPS13A gene.
  • Journal: International journal of molecular sciences
  • Published —
Copper, Iron, and Manganese Toxicity in Neuropsychiatric Conditions.
Clinical Trial
  • Status: Active, not recruiting
  • Phase: Phase 2
  • Intervention Type: Drug
  • Participants: 20
  • Start Date: November 2008
Ferrochelating Treatment in Patients Affected by Neurodegeneration With Brain Iron Accumulation (NBIA)
Clinical Trial
  • Status: Recruiting
  • Participants: 300
  • Start Date: April 2015
NBIAready: Online Collection of Natural History Patient-reported Outcome Measures