Neuropediatrics 2008; 39 - P006
DOI: 10.1055/s-0029-1215775

Clinical characterisation of NBIA patients with and without mutation in PANK2 gene

MB Hartig 1, M Hempel 1, T Meitinger 1, T Kmiec 2, H Prokisch 3
  • 1Institut für Humangenetik, München, Germany
  • 2Memorial Children's Health Institute, Warsaw, Poland
  • 3Helmholtz-Zentrum München, München, Germany

Objective: Neurodegeneration with brain iron accumulation (NBIA) is a heterogeneous group of disorders characterized by iron deposits in the basal ganglia. About half of these patients have mutations in the PANK2 gene causing pantothenate kinase-assocciated neurodegeneration (PKAN). Recently, mutations in the PLA2G6 gene have been identified in few NBIA patients. PKAN patients, PLA2G6 patients and patients without PANK2 gene mutations (idiopathic NBIA) share common clinical symptoms. The aim of our study was to reveal clinical patterns to distinguish these NBIA subgroups.

Method: We present a structured clinical evaluation of a large collection of NBIA patients assessed by one clinician (n=49). In all patients a mutation analysis of the PANK2 gene was completed. PANK2 negative patients underwent PLA2G6 analysis.

Results: In 27 patients homozygous or compound heterozygous mutations were identified in PANK2. No PLA2G6 mutations were found. The „eye of the tiger“ sign was present in the majority of patients (24 out of 27) with PANK2 mutations but rarely in idiopathic NBIA patients (2 out of 22). PKAN patients and idiopathic NBIA patients can be further distinguished by age of onset, loss of gait, the occurrence of generalized dystonia, parkinsonism, cognitive deficits, oromandibular dystonia and dysarthria. Using a statistical analysis based on evaluation of these five clinical parameters it was possible to predict the presence of PANK2 mutations with an accuracy of 85%. This is comparable to the detection of the „eye of the tiger“ sign. Generalized dystonia occurred in 96% of cases with PANK2 mutation as the presenting symptom, but in only 36% of the idiopathic NBIA patients.

Conclusions: Despite shared common clinical symptoms PKAN and idiopathic NBIA patients can be distinguished by „eye of the tiger“ sign, age of onset, generalized dystonia as presenting symptom and occurrence of generalized dystonia, parkinsonism, cognitive deficits, oromandibular dystonia and dysarthria.