Elsevier

Pediatric Neurology

Volume 49, Issue 5, November 2013, Pages 351-354
Pediatric Neurology

Clinical Observations
Idiopathic Basal Ganglia Calcifications: An Atypical Presentation of PKAN

https://doi.org/10.1016/j.pediatrneurol.2013.06.021Get rights and content

Abstract

Background

We report a patient with pantothenate kinase–associated neurodegeneration presenting as idiopathic basal ganglia calcifications, previously known as Fahr's disease.

Methods

A teenage girl presented with slowly progressive dystonia. Her brain magnetic resonance imaging scan revealed T1 and T2 hypointensities in both globus pallidi, and no eye-of-the-tiger sign. Computed tomography showed dense globus pallidi calcifications. Metabolic evaluation was negative. The patient was diagnosed with idiopathic basal ganglia calcifications, a poorly understood syndrome of unknown cause. Whole exome sequencing was performed.

Results

The patient was found to have two mutations in the pantothenate kinase 2 (PANK2) gene that have been previously associated with pantothenate kinase–associated neurodegeneration: a paternally inherited p.G521R and maternally inherited p.T528M. No deleterious changes were identified in genes associated with idiopathic basal ganglia calcifications or dystonia.

Conclusions

Pantothenate kinase–associated neurodegeneration should be considered in patients with idiopathic basal ganglia calcifications, especially when findings are confined to the globus pallidus.

Introduction

Pantothenate kinase–associated neurodegeneration (PKAN) (OMIM #234200), a rare autosomal recessive disorder resulting from mutations in the pantothenate kinase 2 gene (PANK2), is characterized by progressive extrapyramidal dysfunction and iron accumulation in the basal ganglia. The classic eye-of-the-tiger sign seen on T2-weighted magnetic resonance imaging (MRI) scan refers to symmetrical rings of hypointensity representing iron deposition in the globus pallidi, with a central spot of high signal that may be due to gliosis or edema. This characteristic neuroimaging finding has been considered pathognomonic for PKAN.1, 2

Patients with idiopathic basal ganglia calcification (IBGC), previously known as Fahr's disease, experience similar clinical symptoms as those with PKAN, but neuroimaging studies reveal basal ganglia calcifications as opposed to iron deposits. The underlying cause of IBGC remains unknown. We describe a teenage girl with clinical features of IBGC, but who was found to have a compound heterozygote for two disease-causing mutations in exon 6 of the PANK2 gene, confirming a diagnosis of PKAN.

Section snippets

Patient and Methods

A 14-year-old black girl presented with involuntary hand movements and slowly progressive hand, neck, and oromandibular dystonia. She developed subtle behavioral changes including emotional lability and impulsivity. By age 18 she suffered severe dystonia of the jaw, tongue, neck, and arms; significant dysarthria and bradykinesia; and a mildly abnormal gait. Her cognition remained normal, and she was an excellent student. Family history was noncontributory, including two unaffected half maternal

Results

Exome analysis for the family trio did not uncover homozygous recessive or predicted pathogenic de novo changes in disease-associated genes. Examinations of exonic changes present in a compound heterozygote state uncovered two missense mutations in PANK2 (exon6: g.1561G>A + g.1583C>T, p.G521R + p.T528M, transcript uc002wkc.3) of maternal and paternal origin, respectively, leading to changes to highly conserved amino acids that are known to be disease associated with PKAN (Fig 2).4 We also found

Discussion

We report a patient with genetically confirmed PKAN presenting as IBGC, previously known as Fahr's disease. This case illustrates how whole exome sequencing can expand our understanding of rare neurodegenerative syndromes and establishes PANK2 mutations as a newly recognized cause of IBGC. This case also expands the phenotypic spectrum of PKAN to include patients who exhibit globus pallidi calcifications and no eye-of-the-tiger sign.

PKAN accounts for about half of all patients with NBIA.1 In

References (15)

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