PKAN

Pantothenate Kinase-Associated Neurodegeneration

GENE: PANK2;
INHERITANCE: Autosomal recessive;
ONSET: Typically in childhood;
SYMPTOMS: Dystonia, rigidity, dysarthria, and retinal degeneration;
NOTES: The most common form of NBIA, PKAN is characterized by the “eye of the tiger” sign on brain MRI due to iron accumulation in the globus pallidus.

Overview

PKAN is the most common form of NBIA (Neurodegeneration with Brain Iron Accumulation), accounting for approximately 35-50% of all NBIA diagnoses. It is an autosomal recessive disorder caused by mutations in the PANK2 gene, which lead to disruption of normal metabolism in the brain. PKAN exists along a spectrum: there are classic (early onset) and atypical (later onset) forms, with some patients falling in between.

Genetics & Pathophysiology

Gene involved: PANK2 on chromosome 20. Mutations in both copies of this gene are required (autosomal recessive inheritance).
The PANK2 gene encodes the enzyme pantothenate kinase 2, which is essential for the first step in making coenzyme A (CoA) from vitamin B5 (pantothenic acid). Disruption of this pathway leads to metabolic dysfunction.
Iron accumulation: Abnormal iron buildup occurs particularly in the globus pallidus and substantia nigra. One striking MRI sign is called the “eye-of-the-tiger” (a central hyperintensity surrounded by hypointensity in the globus pallidus on T2-weighted MRI).

Clinical Features & Symptoms

Classic PKAN

Onset usually early in childhood (often before age 6, frequently around age 3).
Progressive dystonia, spasticity (stiff muscles), choreoathetosis (twisting, involuntary movements).
Difficulty walking; loss of ambulation often occurs several years after symptom onset. Many classic PKAN patients may become wheelchair dependent during childhood or adolescence.
Speech problems (dysarthria), swallowing difficulties, and oral and facial dystonia (tongue involvement etc.).
Vision involvement: pigmentary retinal degeneration and optic nerve changes.

Atypical PKAN

Symptoms appear later (average onset around early teens or later). More gradual progression.
Speech problems and psychiatric features are more common compared to classic PKAN: mood changes, behavioral issues, emotional lability.
Movement symptoms may progress more slowly; ambulation may be preserved longer, but decline still occurs.

Diagnosis & Imaging

MRI is central: the “eye-of-the-tiger” sign on T2 MRI sequences in the globus pallidus is a hallmark.
Genetic testing confirming PANK2 mutations (biallelic pathogenic variants) is required for definitive diagnosis.
Other diagnostic support: evaluation of movement, speech, swallowing functions; vision exams; monitoring of nutritional status.

Management & Care

There is currently no cure; treatments focus on symptom management and preserving function.
Symptomatic treatments may include medications for dystonia/spasticity, botulinum toxin for focal dystonic muscles, physical and occupational therapies, speech therapy, adaptive equipment.
For severe dystonia or movement issues, deep brain stimulation (DBS) may be considered in some patients.
Supportive care for complications: feeding assistance, respiratory support, nutritional monitoring, management of swallowing difficulties, attention to vision problems.

Research & Emerging Treatments

Clinical guidelines (“Best Practices in PKAN”) have been developed to help clinicians and families with standard care approaches.
Studies continue into disease-modifying approaches, including iron chelation, metabolic pathway correction, and molecular therapies that aim to address PANK2 dysfunction.
Research into systemic biomarkers (oxidative stress, inflammation) is offering insight into disease severity and possible monitoring tools.

Living with PKAN

Living with PKAN can be incredibly challenging, both for affected individuals and their families. Symptoms often steadily worsen, making daily tasks harder over time.

Support involves a multidisciplinary care team, continuous adaptation, and strong community connections. Access to therapies, assistive technology, and genetic counseling can help families navigate the disease.

Aside from medical care, emotional support, peer community, and hope for new treatments are central to many families’ resilience.

Why PKAN Matters

Because PKAN is among the more common NBIA forms, improvements in its care and research often ripple out to benefit the broader NBIA community. Advances in PKAN research may offer insights into other iron accumulation disorders.

Resources

1. GeneReviews: Pantothenate Kinase-Associated Neurodegeneration summary and clinical management.
2. NBIAcure and NBIA Disorders Association: patient support, updated information.
3. Rare diseases databases (GARD, NIH) for up-to-date descriptions and resources.