Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome
- PMID: 12510040
- DOI: 10.1056/NEJMoa020817
Genetic, clinical, and radiographic delineation of Hallervorden-Spatz syndrome
Abstract
Background: Hallervorden-Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and iron accumulation in the brain. Many patients with this disease have mutations in the gene encoding pantothenate kinase 2 (PANK2); these patients are said to have pantothenate kinase-associated neurodegeneration. In this study, we compared the clinical and radiographic features of patients with Hallervorden-Spatz syndrome with and without mutations in PANK2.
Methods: One hundred twenty-three patients from 98 families with a diagnosis of Hallervorden-Spatz syndrome were classified on the basis of clinical assessment as having classic disease (characterized by early onset with rapid progression) or atypical disease (later onset with slow progression). Their genomic DNA was sequenced for PANK2 mutations.
Results: All patients with classic Hallervorden-Spatz syndrome and one third of those with atypical disease had PANK2 mutations. Whereas almost all mutations in patients with atypical disease led to amino acid changes, those in patients with classic disease more often resulted in predicted protein truncation. Patients with atypical disease who had PANK2 mutations were more likely to have prominent speech-related and psychiatric symptoms than patients with classic disease or mutation-negative patients with atypical disease. In all patients with pantothenate kinase-associated neurodegeneration, whether classic or atypical, T2-weighted magnetic resonance imaging (MRI) of the brain showed a specific pattern of hyperintensity within the hypointense medial globus pallidus. This pattern was not seen in any patients without mutations.
Conclusions: PANK2 mutations are associated with all cases of classic Hallervorden-Spatz syndrome and one third of cases of atypical disease. A specific MRI pattern distinguishes patients with PANK2 mutations. Predicted levels of pantothenate kinase 2 protein correlate with the severity of disease.
Copyright 2003 Massachusetts Medical Society
Comment in
-
Hallervorden and history.N Engl J Med. 2003 Jan 2;348(1):3-4. doi: 10.1056/NEJMp020158. N Engl J Med. 2003. PMID: 12510036 No abstract available.
Similar articles
-
Unraveling the Hallervorden-Spatz syndrome: pantothenate kinase-associated neurodegeneration is the name.Curr Opin Pediatr. 2003 Dec;15(6):572-7. doi: 10.1097/00008480-200312000-00005. Curr Opin Pediatr. 2003. PMID: 14631201 Review.
-
Brain MRI in neurodegeneration with brain iron accumulation with and without PANK2 mutations.AJNR Am J Neuroradiol. 2006 Jun-Jul;27(6):1230-3. AJNR Am J Neuroradiol. 2006. PMID: 16775270 Free PMC article.
-
Clinical heterogeneity of neurodegeneration with brain iron accumulation (Hallervorden-Spatz syndrome) and pantothenate kinase-associated neurodegeneration.Mov Disord. 2004 Jan;19(1):36-42. doi: 10.1002/mds.10650. Mov Disord. 2004. PMID: 14743358
-
Siblings with the adult-onset slowly progressive type of pantothenate kinase-associated neurodegeneration and a novel mutation, Ile346Ser, in PANK2: clinical features and (99m)Tc-ECD brain perfusion SPECT findings.J Neurol Sci. 2010 Mar 15;290(1-2):172-6. doi: 10.1016/j.jns.2009.11.008. Epub 2009 Dec 14. J Neurol Sci. 2010. PMID: 20006850
-
Novel PANK2 mutation in a Chinese boy with PANK2-associated neurodegeneration: A case report and review of Chinese cases.Medicine (Baltimore). 2019 Jan;98(4):e14122. doi: 10.1097/MD.0000000000014122. Medicine (Baltimore). 2019. PMID: 30681573 Free PMC article. Review.
Cited by
-
Pseudo eye of the tiger sign in atypical parkinsonism.Neurol Sci. 2013 May;34(5):777-8. doi: 10.1007/s10072-012-1113-y. Epub 2012 May 20. Neurol Sci. 2013. PMID: 22610524 No abstract available.
-
Cerebral blood flow in dystonia due to pantothenate kinase-associated neurodegeneration.Neuroradiol J. 2020 Dec;33(6):479-485. doi: 10.1177/1971400920943967. Epub 2020 Aug 27. Neuroradiol J. 2020. PMID: 32851917 Free PMC article.
-
The Case of a Patient with Pantothenate Kinase-Associated Neurodegeneration Presenting with a Prolonged History of Stuttering Speech and a Misdiagnosis of Parkinson's Disease.J Mov Disord. 2021 Jan;14(1):86-88. doi: 10.14802/jmd.20062. Epub 2020 Sep 21. J Mov Disord. 2021. PMID: 32942839 Free PMC article. No abstract available.
-
Novel PANK2 gene mutations in two Chinese siblings with atypical pantothenate kinase-associated neurodegeneration.Neurol Sci. 2013 Apr;34(4):561-3. doi: 10.1007/s10072-012-1177-8. Epub 2012 Aug 29. Neurol Sci. 2013. PMID: 22930366
-
Diagnostic and clinical experience of patients with pantothenate kinase-associated neurodegeneration.Orphanet J Rare Dis. 2019 Jul 12;14(1):174. doi: 10.1186/s13023-019-1142-1. Orphanet J Rare Dis. 2019. PMID: 31300018 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases