Pantathenate kinase deficiency Associated Neurodegeneration

Synonysms:

Pantathenate kinase associated neurodegeneration PKAN a.k.a. Pantathenate kinase PANK deficiency a.k.a. Pantathenate kinase PANK deficiency a.k.a. Neurodegeneration with brain iron accumulation type 1 NBIA1, formerly Hallervorden-Spatz disease, rare:

Diagnosis:

Genetics:

  • Sporadic or autosomal recessive
  • PANK2 gene Chr. 20p13. Protein= pantothenate kinase (involved in coenzyme A biosythesis, panthothenate= vitamin B5)

Clinical features:

  • Childhood onset usually but may present in adulthood
  • Ridigity, difficulty walking, dysarthria, dementia,
  • Psychiatic symptoms: depression, behavioural problems

Findings on investigations:

MRI:

  • T2: external globus pallidus bilateral hyperintensities with surrounding hypointensity a.k.a. “eye of the tiger sign”
  • Generalised atrophy
  • Other tests:
    • Blood smear: increased acanthocytes

Pathology:

Gross: discolouration of the medial globus pallidus & substantia nigra. Atrophy of cerebral cortex, brain stem & cerebellum
Microscopically: axonal spheroids, neuronal loss & astrocytosis in the medial globus pallidus & substatia nigra. Spheroids also occur in the cerebral cortex, thalamus, subthalamus, striatum, brainstem & spinal cord,
Iron deposition in spheroids, neurons, microglia & vessels.
Immunohistochemistry: spheroids are positive for ferritin, ubiquitin, amyloid precursor protein, neurofilament and alpha synuclein.

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