Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration

Madhavi Thomas, Susan J. Hayflick, Joseph Jankovic

Research output: Contribution to journalReview article

115 Scopus citations

Abstract

Hallervorden Spatz syndrome (HSS), also referred to as neurodegeneration with brain iron accumulation (NBIA), is a rare inherited neurodegenerative disorder with childhood, adolescent, or adult onset. Patients with HSS/NBIA have a combination of motor symptoms in the form of dystonia, parkinsonism, choreoathetosis, corticospinal tract involvement, optic atrophy, pigmentary retinopathy, and cognitive impairment. After the recent identification of mutations in the PANK2 gene on chromosome 20p12.3-p13 in some patients with the HSS/NBIA phenotype, the term pantothenate kinase-associated neurodegeneration (PKAN) has been proposed for this group of disorders. To characterize clinically and genetically HSS/NBIA, we reviewed 34 affected individuals from 10 different families, who satisfied the inclusion criteria for NBIA. Relatives of patients who had clinical, magnetic resonance imaging (MRI), or pathological findings of NBIA were included in the study. Four patients were found to have mutations in the pantothenate kinase 2 (PANK2) gene. We compared the clinical features and MRI findings of those with and without PANK2 mutations. The presence of mutation in the PANK2 gene is associated with younger age at onset and a higher frequency of dystonia, dysarthria, intellectual impairment, and gait disturbance. Parkinsonism is seen predominantly in adult-onset patients whereas dystonia seems more frequent in the earlier-onset cases. The phenotypic heterogeneity observed in our patients supports the notion of genetic heterogeneity in the HSS/NBIA syndrome.

Original languageEnglish (US)
Pages (from-to)36-42
Number of pages7
JournalMovement Disorders
Volume19
Issue number1
DOIs
StatePublished - Jan 1 2004

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Keywords

  • Brain iron accumulation
  • Hallervorden Spatz syndrome
  • NBIA
  • Neurodegeneration
  • PKAN
  • Pantothenate kinase-associated neurodegeneration

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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