Genetic, Clinical, and Radiographic Delineation of Hallervorden–Spatz Syndrome

• Published in: The New England journal of medicine Vol. 348; no. 1; pp. 33 - 40
• Main Authors: Hayflick, Susan J, Westaway, Shawn K, Levinson, Barbara, Zhou, Bing, Johnson, Monique A, Ching, Katherine H.L, Gitschier, Jane
• Format: Journal Article
• Language: English
• Published: Boston, MA Massachusetts Medical Society 02-01-2003
• Subjects: Age of Onset; Biological and medical sciences; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Diagnosis, Differential; Disease; Disease Progression; Enzymes; Founder Effect; Genes; Genetics; Humans; Magnetic Resonance Imaging; Medical sciences; Mutation; Mutation, Missense; Neurology; Pantothenate Kinase-Associated Neurodegeneration - complications; Pantothenate Kinase-Associated Neurodegeneration - diagnosis; Pantothenate Kinase-Associated Neurodegeneration - genetics; Pantothenate Kinase-Associated Neurodegeneration - psychology; Phosphotransferases (Alcohol Group Acceptor) - genetics; Speech Disorders - etiology; Human; Nervous system diseases; Radiodiagnosis; Radiologic sign; Stage classification; Clinical form; Case control study; Genetic determinism; Nuclear magnetic resonance imaging; Cerebral disorder; Genetic disease; Infection; Radiography; Specificity; Viral disease; Autosomal character; Central nervous system disease; Recessive character; Mutation; Hallervorden Spatz disease; Brain (vertebrata); Pantothenic acid
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMoa020817

Hallervorden–Spatz syndrome is an autosomal recessive disorder characterized by dystonia, parkinsonism, and brain iron accumulation. The authors found that all patients with classic disease (characterized by early onset and rapid progression) and one third of patients with atypical disease (later onset and slow progression) had mutations in the gene encoding pantothenate kinase 2 (
PANK2
). All patients with
PANK2
mutations had a characteristic abnormality on magnetic resonance imaging of the brain.
The diagnosis of Hallervorden–Spatz syndrome applies to a spectrum of disorders that share the common features of neurodegeneration and iron accumulation in the brain.
1
,
2
Hallervorden–Spatz syndrome with early onset and rapid progression is the originally reported, classic form of the disease.
3
It presents in childhood with dystonia, dysarthria, and rigidity and has a relentlessly progressive course, culminating in early death. Pigmentary degeneration of the retina may accompany this form of the disease, and iron deposition in the basal ganglia is evident on magnetic resonance imaging (MRI) and postmortem examination.
1
In an atypical form of Hallervorden–Spatz syndrome, the onset of . . .