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

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.

Authors+Show Affiliations

Department of Pediatric Neurology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany.Department of Human Genetics, University of Leipzig Faculty of Medicine, Leipzig, Sachsen, Germany.Division of Pediatric Radiology, University Hospital Leipzig, Leipzig, Sachsen, Germany.Department of Pediatric Endocrinology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany.Department of Human Genetics, Praxis für Humangenetik Leipzig, Leipzig, Sachsen, Germany.Department of Pediatric Neurology, Leipzig University Hospital for Children and Adolescents, Leipzig, Sachsen, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31505688

Citation

Hornemann, Frauke, et al. "Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration." Neuropediatrics, 2019.
Hornemann F, Le Duc D, Roth C, et al. Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration. Neuropediatrics. 2019.
Hornemann, F., Le Duc, D., Roth, C., Pfäffle, R., Huhle, D., & Merkenschlager, A. (2019). Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration. Neuropediatrics, doi:10.1055/s-0039-1696688.
Hornemann F, et al. Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration. Neuropediatrics. 2019 Sep 10; PubMed PMID: 31505688.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Childhood Dystonia-Parkinsonism Following Infantile Spasms-Clinical Clue to Diagnosis in Early Beta-Propeller Protein-Associated Neurodegeneration. AU - Hornemann,Frauke, AU - Le Duc,Diana, AU - Roth,Christian, AU - Pfäffle,Roland, AU - Huhle,Dagmar, AU - Merkenschlager,Andreas, Y1 - 2019/09/10/ PY - 2019/9/11/entrez PY - 2019/9/11/pubmed PY - 2019/9/11/medline JF - Neuropediatrics JO - Neuropediatrics N2 - 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. SN - 1439-1899 UR - https://www.unboundmedicine.com/medline/citation/31505688/Childhood_Dystonia-Parkinsonism_Following_Infantile_Spasms-Clinical_Clue_to_Diagnosis_in_Early_Beta-Propeller_Protein-Associated_Neurodegeneration L2 - http://www.thieme-connect.com/DOI/DOI?10.1055/s-0039-1696688 DB - PRIME DP - Unbound Medicine ER -