Objective: Recall a case of genetic late-onset cerebellar ataxia with a specific clinical and radiological feature highly suggestive of Pantothenate-kinase-associated neurodegeneration(PKAN).

Background: Cerebellar ataxia is a frequent symptom that can be classified as acquired or genetic. Although an earlier age at onset (AO) is more suggestive, a genetic cause should be suspected with a later AO in some specific cases.

Method: We report a case of a 30-year-old (yo) female who presented with gait disorders. PKAN diagnosis was made after clinical and radiological investigations.

Results: A 30-yo female, from a consanguineous marriage, presented with gait disorders that had progressively worsened. Her family history revealed similar cases of ataxia in her mother, sister, brother and aunt that had appeared at the age of 35yo, 17yo, 27yo and 25yo respectively. Examination revealed a static and kinetic cerebellar syndrome. Cerebral MRI revealed a bilateral and symmetrical hypointensities of the globus pallidus (GP) and substantia nigra (SN) on T2*, T2 FLAIR and T2 weighted images, with a central hyperintensity in GP defining the eye-of-the-tiger sign, characteristic of PKAN. PKAN diagnosis was the most probable even with a late-onset ataxia, given the positive family history and typical radiological features.

Conclusion: PKAN is a rare genetic disorder and the most common form of neurodegeneration with brain iron accumulation with an autosomal recessive inheritance. It is caused by PANK2 gene mutations and begins in the first two decades with progressive extrapyramidal manifestations. Although a later AO has been rarely described, the diagnosis is suspected with a positive family history, defining an atypical PKAN. The latter is characterized by a slower disease progression, more frequent psychiatric symptoms and gait abnormalities. Although definitive diagnosis is a pathogenic mutation, in the appropriate clinical context, neuroimaging clues and serum markers can facilitate targeted gene testing. In fact, a characteristic MRI finding in PKAN is the eye-of-the-tiger sign, which is an abnormal iron accumulation seen as diffuse and bilateral low T2 weighted signal intensity in SN and GP surrounding a central area of high T2 weighted signal intensity in the anteromedial GP corresponding to gliosis. It is correlated with a positive PANK2 mutation due to its high specificity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/late-onset-cerebellar-ataxia-revealing-a-pantothenate-kinase-associated-neurodegeneration/