Pantothenate Kinase-Associated Neurodegeneration (PKAN) Differential Diagnoses

Updated: Dec 07, 2016
  • Author: Philip A Hanna, MD; Chief Editor: Selim R Benbadis, MD  more...
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Diagnostic ConsiderationsWilson diseaseJuvenile form of Huntington diseaseJuvenile neuronal ceroid lipofuscinosisMachado-Joseph diseaseNeuroacanthocytosisGM gangliosidoses

The differential diagnosis of pantothenate kinase-associated neurodegeneration (PKAN) includes other diseases presenting with extrapyramidal-pyramidal-dementia complex.

Wilson disease usually presents with tremors, rigidity, dementia, and pseudobulbar features and has an autosomal recessive mode of inheritance. Slit-lamp examination of the eyes may reveal a Kayser-Fleischer ring. MRI in Wilson disease exhibits the characteristic changes consisting of high-intensity lesions in the basal ganglia, thalami, and mid brain on T2-weighted images. The normal low intensity of red nuclei and SN surrounded by abnormal high-signal intensity in the tegmentum of the mid brain gives rise to the typical "face-of-the-giant-panda" sign. Results from serum ceruloplasmin and copper studies are usually abnormal and help to confirm the diagnosis. Neurologic symptoms are reversible if treated early with copper chelation therapy; hence, an early diagnosis is important.

The juvenile form of Huntington disease may be confused with PKAN. Patients with this form of Huntington disease present with a predominantly akinetic-rigid syndrome (ie, Westphal variant). The differentiating features include an autosomal dominant mode of inheritance and the presence of caudate atrophy on MRI.

Juvenile neuronal ceroid lipofuscinosis may be difficult to distinguish from PKAN. It is an inherited disorder characterized by storage of ceroid and lipofuscin in neuronal and other tissues. The symptoms start in early childhood with vision loss, retinitis pigmentosa, dementia, rigidity, and dystonia. In contrast to the infantile and late-infantile forms of the disease, generalized tonic-clonic seizures and myoclonic seizures are not very common.

The diagnosis can be made on the basis of clinical presentation, electrophysiologic studies, and skin biopsy findings. The electroretinogram reveals markedly reduced amplitude, and visual and somatosensory evoked responses are increased. The characteristic fingerprint inclusion bodies are identified easily in eccrine sweat glands and in circulating lymphocytes.

Machado-Joseph disease is inherited as an autosomal dominant trait, and the onset of clinical disease is usually later, after age 20 years. Ataxia and other signs of spinocerebellar dysfunction are predominant. Some affected children may have extrapyramidal features, but prominent ataxia and the inheritance pattern help to differentiate Machado-Joseph disease from PKAN.

Neuroacanthocytosis is characterized by onset in the third or fourth decade and prominent orofacial dyskinesia, chorea, dystonia, and cognitive changes. Other features include self-mutilation, peripheral neuropathy, and seizures. Recognition of acanthocytes (red blood cells with irregular spine on the cell surface) in the peripheral smear can lead to the diagnosis.

Rare metabolic disorders such as GM1 and GM2 gangliosidoses in children sometimes can have features similar to PKAN, but they have other clinical features and lab abnormalities and are differentiated readily.

Differential Diagnoses