PANK2

Pantothenate kinase-associated neurodegeneration

About 100 mutations in the PANK2 gene have been identified in people with pantothenate kinase-associated neurodegeneration. Typically, people with the more severe, early-onset form of the disorder have PANK2 mutations that prevent cells from producing any functional pantothenate kinase 2. People affected by the atypical, later-onset form usually have mutations that change single amino acids in the enzyme, which makes the enzyme unstable or disrupts its activity. In some cases, single amino acid changes allow the enzyme to retain some function. The most common PANK2 mutation replaces the amino acid glycine with the amino acid arginine at position 411 of the enzyme (written as Gly411Arg or G411R).

When pantothenate kinase 2 is altered or missing, the normal production of coenzyme A is disrupted and potentially harmful compounds can build up in the brain. This buildup leads to swelling, tissue damage, and an abnormal accumulation of iron in certain areas of the brain. Researchers are uncertain how a lack of functional pantothenate kinase 2 causes the specific features of pantothenate kinase-associated neurodegeneration. Because the enzyme functions in mitochondria, the signs and symptoms of this condition may be related to impaired energy production.

Mutations in the PANK2 gene are also found in people with a condition called HARP (hypoprebetalipoproteinemia, acanthocytosis, retinitis pigmentosa, and pallidal degeneration). HARP was historically described as a separate syndrome but 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.