Pantothenate Kinase-Associated Neurodegeneration (PKAN)
Description
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a rare, inherited neurodegenerative disorder characterized by progressive neurological decline. This condition primarily affects the basal ganglia, a critical brain region involved in movement control. This blog delves into the intricacies of PKAN, exploring its symptoms, causes, diagnosis, management strategies, and resources for individuals and families impacted by this disorder.
Genes Involved
PKAN is caused by mutations in the PANK2 gene. This gene provides instructions for making an enzyme called pantothenate kinase 2 (PANK2). This enzyme plays a crucial role in the production of coenzyme A (CoA), an essential molecule involved in numerous metabolic processes. Mutations in the PANK2 gene can lead to a deficiency of PANK2, which disrupts CoA synthesis and ultimately causes the neurological damage associated with PKAN.
Recognizing the Signs and Symptoms
PKAN symptoms can manifest in various ways and often appear in early childhood, although they can develop later. Some common signs and symptoms include:
- Movement Disorders: Difficulty with walking, balance, and coordination; involuntary movements such as tremors, spasms, or rigidity; slow or stiff movements (bradykinesia);
- Speech Impairment: Slurred speech, difficulty finding words, or a change in voice;
- Vision Problems: Eye movements may be affected, leading to strabismus (crossed eyes) or difficulty with visual tracking; nystagmus (involuntary eye movements) may also occur;
- Cognitive Decline: Memory problems, learning difficulties, and behavioral changes may arise;
- Seizures: In some cases, individuals with PKAN may experience seizures, which can vary in frequency and severity.
It‘s important to note that the severity and progression of symptoms can vary significantly among individuals with PKAN.
Causes
PKAN is caused by mutations in the PANK2 gene, which disrupts the production of pantothenate kinase 2 (PANK2), an enzyme critical for the synthesis of coenzyme A (CoA). CoA is essential for many metabolic functions, including the breakdown of fatty acids, the production of energy, and the synthesis of neurotransmitters. The deficiency of PANK2 leads to the accumulation of toxic byproducts in the brain, resulting in the neurological damage characteristic of PKAN.
Inheritance/recurrence risk
PKAN is an autosomal recessive disorder, meaning both parents must carry a copy of the mutated PANK2 gene for their child to inherit the condition. If both parents are carriers, there is a 25% chance with each pregnancy that their child will inherit the disorder.
Carrier testing can help determine if individuals are carriers of the mutated PANK2 gene, which can be important for family planning and genetic counseling.
