Pantothenate kinase-associated neurodegeneration

Pantothenate kinase-associated neurodegeneration (PKAN), formerly called Hallervorden–Spatz syndrome, is a genetic degenerative disease of the brain that can lead to parkinsonism, dystonia, dementia, and ultimately death. Neurodegeneration in PKAN is accompanied by an excess of iron that progressively builds up in the brain.

PKAN is caused by loss of function of the enzyme PANK2, due to bi-allelic genetic mutations. It follows autosomal recessive inheritance. This enzyme is the first step in the pathway converting vitamin B5 into coenzyme A. There are currently no treatments that modify disease progress, though there are a number of medications and therapies that can help improve symptoms and there is active research into treatments.

Signs and symptoms

Symptoms typically begin in childhood and are progressive, often resulting in death by early adulthood. Symptoms of PKAN begin before middle childhood, and most often are noticed before ten years of age. Symptoms include:

dystonia (repetitive uncontrollable muscle contractions that may cause jerking or twisting of certain muscle groups)

dysphagia & dysarthria due to muscle groups involved in speech being involved

rigidity/stiffness of limbs

tremor

writhing movements

dementia

spasticity

weakness

seizures (rare)

toe walking

retinitis pigmentosa, another degenerative disease that affects the individual's retina, often causing alteration of retinal color and progressive deterioration of the retina at first causing night blindness and later resulting in a complete loss of vision.

25% of individuals experience an uncharacteristic form of PKAN that develops post-10 years of age and follows a slower, more gradual pace of deterioration than those pre-10 years of age. These individuals face significant speech deficits as well as psychiatric and behavioral disturbances.