PKAN is a progressive disorder. Lost skills are usually not regained. The rate of progression correlates with age at onset: those with early symptoms decline more rapidly. As the disease advances, dystonia and spasticity compromise the child’s ability to ambulate; most of those with early-onset disease are wheelchair bound by the mid-teens, and some much earlier. PKAN progresses at a non-uniform rate. Affected individuals experience episodes of rapid deterioration, often lasting one to two months, interspersed with longer periods of stability. Common causes of stress and catabolism do not seem to correlate with periods of decline, a phenomenon for which no cause has been found.
Premature death does occur. However, life span is variable; with improvements in medical care, a greater number of affected individuals are living into adulthood. Orofacial dystonia can result in the secondary effects of swallowing difficulty and poor nutrition. Premature death is more likely related to these secondary effects (e.g., nutrition-related immunodeficiency, aspiration pneumonia) than to the primary neurodegenerative process.
Classic PKAN. The neurologic signs and symptoms of early-onset, rapidly progressive (classic) pantothenate kinase-associated neurodegeneration (PKAN) are primarily extrapyramidal and include dystonia, dysarthria, and rigidity.
Dystonia is always present and usually an early manifestation. Cranial and limb dystonia are frequent and may lead, respectively, to recurrent trauma to the tongue, in some cases requiring full-mouth dental extraction, or to atraumatic long bone fracture from the combination of extreme bone stress and osteopenia.
Corticospinal tract involvement is common and includes spasticity, hyperreflexia, and extensor toe signs.
Seizures are rare.
Intellectual impairment may be a major feature of PKAN. A study of 16 children and adults with PKAN showed varied cognitive expression as measured by standardized evaluation tools, with skills ranging from high average to markedly below average. Age of onset had a strong inverse correlation with intellectual impairment (i.e., earlier onset was associated with greater impairment) [Freeman et al 2007]. However, a more recent study of cognitive function in a population of individuals with PKAN undergoing deep brain stimulation suggests that cognitive decline may be overestimated in those with PKAN. The authors proposed that this is due to difficulty accessing cognition in those with PKAN because of the severity of their motor impairments.
Pigmentary retinal degeneration occurs in two thirds of affected individuals with classic PKAN. The retinal degeneration follows a typical clinical course, with nyctalopia (night blindness) followed by progressive loss of peripheral visual fields and sometimes eventual blindness. Evaluation by electroretinogram often detects retinal changes that are asymptomatic.
Optic atrophy is rarely seen in PKAN. Abnormal eye movements, including vertical saccades and saccadic pursuits, are common. In one study, eight of ten individuals with PKAN had sectoral iris paralysis and partial loss of the pupillary ruff consistent with bilateral Adie’s pupil
The clinical features of classic PKAN are remarkably homogeneous. It presents in early childhood, usually before age six years (mean age: 3.4 years). The most common presenting symptom is impaired gait resulting from a combination of lower-extremity rigidity, dystonia, and spasticity, as well as restricted visual fields in those children with retinopathy. Some children have developmental delay, which is primarily motor but occasionally global. Visual symptoms may bring children with PKAN to medical attention. Toe-walking and upper-extremity dystonia are less common presenting signs.