title: Phenotypic spectrum of neurodegeneration associated with mutations in the PLA2G6 gene (PLAN).
abstract: BACKGROUND
  Neurodegeneration associated with brain iron accumulation (NBIA) comprises a heterogeneous group of disorders in which disruption of cellular mechanisms leads to accumulation of iron in the basal ganglia. This group includes patients with recently discovered mutations in the PLA2G6 gene encoding a calcium-independent phospholipase A2 enzyme that catalyzes the hydrolysis of glycerophospholipids. Previously, children with PLA2G6 mutations have been diagnosed with several different disorders and we wished to better define the phenotype of PLA2G6- associated neurodegeneration.
  
  
  METHODS
  Detailed review of the clinical and genetic features of 14 and radiologic features of 13 of these patients with PLA2G6 mutations was undertaken.
  
  
  RESULTS
  Median age of symptom presentation was 14 months. One third of the cohort presented following an intercurrent illness. The children had progressive cognitive and motor skill regression, with evidence of axial hypotonia, four limb spasticity, bulbar dysfunction, and strabismus. All patients developed cerebellar ataxia and dystonia. Most patients had optic atrophy. Brain imaging demonstrated cerebellar cortical atrophy and gliosis in all patients. Changes consistent with increased iron deposition were identified in the globus pallidus and substantia nigra. Novel corpus callosum changes are also reported.
  
  
  CONCLUSIONS
  We describe a cohort of patients with PLA2G6-associated neurodegeneration (PLAN). Although patients with PLAN have previously been diagnosed with infantile neuroaxonal dystrophy, neurodegeneration associated with brain iron accumulation, and Karak syndrome, they display a characteristic clinical and radiologic phenotype. PLA2G6 mutational analysis will negate the need for more invasive diagnostic procedures such as tissue biopsy.
authors.affiliation: Department of Pediatric Neurology, Birmingham Children's Hospital, Birmingham, UK.
authors.forename: M A
authors.initials: MA
authors.lastname: Kurian
authors.forename: N V
authors.initials: NV
authors.lastname: Morgan
authors.forename: L
authors.initials: L
authors.lastname: MacPherson
authors.forename: K
authors.initials: K
authors.lastname: Foster
authors.forename: D
authors.initials: D
authors.lastname: Peake
authors.forename: R
authors.initials: R
authors.lastname: Gupta
authors.forename: S G
authors.initials: SG
authors.lastname: Philip
authors.forename: C
authors.initials: C
authors.lastname: Hendriksz
authors.forename: J E V
authors.initials: JE
authors.lastname: Morton
authors.forename: H M
authors.initials: HM
authors.lastname: Kingston
authors.forename: E M
authors.initials: EM
authors.lastname: Rosser
authors.forename: E
authors.initials: E
authors.lastname: Wassmer
authors.forename: P
authors.initials: P
authors.lastname: Gissen
authors.forename: E R
authors.initials: ER
authors.lastname: Maher
mesh_terms: D017668:Age of Onset; D018912:Arabs / Q000235:genetics; D001284:Atrophy; D001479:Basal Ganglia / Q000737:chemistry*; D001921:Brain / Q000473:pathology; D015331:Cohort Studies; D003241:Consanguinity; D003337:Corpus Callosum / Q000473:pathology; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004739:England / Q000453:epidemiology; D005260:Female; D054522:Group VI Phospholipases A2 / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D007223:Infant; D007501:Iron / Q000032:analysis*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D019150:Neuroaxonal Dystrophies / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D010154:Pakistan / Q000208:ethnology; D010641:Phenotype; D011859:Radiography; D013577:Syndrome; D044465:White People / Q000235:genetics
chemical_list: D007501:Iron; D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human