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Neuropediatrics 2020; 51(01): 022-029
DOI: 10.1055/s-0039-1696688
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Childhood Dystonia-Parkinsonism Following Infantile Spasms—Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration

Frauke Hornemann
1   Department of Pediatric Neurology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany
,
Diana Le Duc
2   Department of Human Genetics, University of Leipzig Faculty of Medicine, Leipzig, Sachsen, Germany
,
Christian Roth
3   Division of Pediatric Radiology, University Hospital Leipzig, Leipzig, Sachsen, Germany
,
Roland Pfäffle
4   Department of Pediatric Endocrinology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany
,
Dagmar Huhle
5   Department of Human Genetics, Praxis für Humangenetik Leipzig, Leipzig, Sachsen, Germany
,
Andreas Merkenschlager
1   Department of Pediatric Neurology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany
› Author Affiliations
Further Information

Publication History

28 April 2019

01 August 2019

Publication Date:
10 September 2019 (online)

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Abstract

Introduction Beta-propeller protein-associated neurodegeneration (BPAN) is a very rare, X-linked dominant (XLD) inherited member of the neurodegeneration with brain iron accumulation (NBIA) disease family.

Case report We present a female case of BPAN with infantile spasms in the first year, Rett-like symptomatology, focal epilepsy, and loss of motor skills in childhood. Menarche occurred at the age of 9, after precocious pubarche and puberty.

Dystonia-parkinsonism as extrapyramidal sign at the age of 10 years resulted in radiological and genetic work-up.

Results Burke–Fahn–Marsden Dystonia Rating Scale (BFMDRS) measured 66/120 points in body part-related dystonia symptoms. Cerebrospinal fluid examination showed dopamine depletion.

T2 and B0 sequences of the diffusion-weighted magnetic resonance imaging showed susceptibility artifacts with NBIA-typical hypointense globus pallidus (GP) and substantia nigra (SN). Next-generation sequencing revealed a BPAN-causing pathogenic variant in WDR45 (WD repeat-containing protein 45) gene (c.830 + 1G > A, XLD, heterozygous, de novo). Skewed X-inactivation was measured (2:98).

Conclusions Autophagy-related X-linked BPAN disease might still be underdiagnosed in female cases of infantile spasms.

Skewed X-inactivation will have mainly influenced the uncommon, very early childhood neurodegenerative symptomatology in the present BPAN case. Oral levodopa substitution led to improvement in sleep disorder, hypersalivation, and swallowing.

Reduced white matter and hypointense signals in SN and GP on susceptibility sequences in magnetic resonance imaging are characteristic radiological findings of advanced disease in NBIA. No BPAN-typical halo sign in T1-weighted scan at midbrain level was seen at the age of 11 years. NBIA panel is recommended for early diagnosis.

Keywords

BPAN - parkinsonism - WDR45 - neurodegeneration - dopamine - infantile spasms
 

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