Basal ganglia calcification in a patient with beta-propeller protein-associated neurodegeneration

Abstract

Background: Beta-propeller protein-associated neurodegeneration is a newly described X-linked dominant condition due to heterozygous mutations in WDR45. The condition is associated with characteristic changes on brain magnetic resonance imaging. Previous literature relating to this disorder has not specifically referred to intracranial calcification.

Methods: A female patient presented with significant developmental delay in early childhood and subsequently demonstrated neurodegeneration with progressive dystonia and dementia in her third decade. Brain magnetic resonance imaging revealed low signal in the substantia nigra and both globus pallidi on T2-weighted imaging, with no eye-of-the-tiger sign. Computed tomography revealed bilateral dense calcification of the globus pallidus. We performed Sanger sequencing of the WDR45 gene in the patient and her parents.

Results: We identified a heterozygous c.488del C p.Pro163Argfs*34 variant in exon 8 of WDR45. Neither parent carried the same mutation, indicating that the molecular change had occurred de novo.

Conclusions: Although the characteristic features of beta-propeller protein-associated neurodegeneration were present in our patient, the observation of basal ganglia calcification was considered atypical. Previous descriptions of basal ganglia calcification in individuals with neuronal brain iron accumulation led us to review the frequency of calcification in these disorders.

Keywords: WDR45; basal ganglia calcification; beta-propeller protein-associated neurodegeneration (BPAN); neurodegeneration with brain iron accumulation (NBIA).