Clinical features and blood iron metabolism markers in children with beta-propeller protein associated neurodegeneration

• Published in: European journal of paediatric neurology Vol. 28; pp. 81 - 88
• Main Authors: Belohlavkova, Anezka, Sterbova, Katalin, Betzler, Cornelia, Burkhard, Stuve, Panzer, Axel, Wolff, Markus, Lassuthova, Petra, Vlckova, Marketa, Kyncl, Martin, Benova, Barbora, Jahodova, Alena, Kudr, Martin, Goerg, Maria, Dusek, Petr, Seeman, Pavel, Kluger, Gerhard, Krsek, Pavel
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2020
• Subjects: Beta-propeller protein-associated neurodegeneration; Biomarkers - blood; Carrier Proteins - genetics; Child; Epilepsy - blood; Epilepsy - genetics; Epilepsy - metabolism; Female; Humans; Intellectual Disability - blood; Intellectual Disability - genetics; Intellectual Disability - metabolism; Iron - blood; Iron Metabolism Disorders - blood; Iron Metabolism Disorders - genetics; Iron Metabolism Disorders - metabolism; Male; Movement Disorders - blood; Movement Disorders - genetics; Movement Disorders - metabolism; Neurodegeneration with brain iron accumulation WDR45, BPAN; Neurodegenerative Diseases - blood; Neurodegenerative Diseases - genetics; Neurodegenerative Diseases - metabolism; Phenotype; Targeted gene panel sequencing; Targeted gene panel sequencing; BPAN; WDR45; Beta-propeller protein-associated neurodegeneration; Neurodegeneration with brain iron accumulation WDR45, BPAN; sTfr/log ferrit
• ISSN: 1090-3798; 1532-2130; 1532-2130
• DOI: 10.1016/j.ejpn.2020.07.010

Neurodegeneration with brain iron accumulation constitutes a group of rare progressive movement disorders sharing intellectual disability and neuroimaging findings as common denominators. Beta-propeller protein-associated neurodegeneration (BPAN) represents approximately 7% of the cases, and its first signs are typically epilepsy and developmental delay. We aimed to describe in detail the phenotype of BPAN with a special focus on iron metabolism. We present a cohort of paediatric patients with pathogenic variants of WD-Repeat Domain 45 gene (WDR45). The diagnosis was established by targeted panel sequencing of genes associated with epileptic encephalopathies (n = 9) or by Sanger sequencing of WDR45 (n = 1). Data on clinical characteristics, molecular-genetic findings and other performed investigations were gathered from all participating centres. Markers of iron metabolism were analysed in 6 patients. Ten children (3 males, 7 females, median age 8.4 years) from five centres (Prague, Berlin, Vogtareuth, Tubingen and Cologne) were enrolled in the study. All patients manifested first symptoms (e.g. epilepsy, developmental delay) between 2 and 31 months (median 16 months). Seven patients were seizure-free (6 on antiepileptic medication, one drug-free) at the time of data collection. Neurological findings were non-specific with deep tendon hyperreflexia (n = 4) and orofacial dystonia (n = 3) being the most common. Soluble transferrin receptor/log ferritin ratio was elevated in 5/6 examined subjects; other parameters of iron metabolism were normal. Severity of epilepsy often gradually decreases in BPAN patients. Elevation of soluble transferrin receptor/log ferritin ratio could be another biochemical marker of the disease and should be explored by further studies. •First study focusing on potential alterations in blood iron metabolism in BPAN.•Elevation of sTfr/log ferrit – possible new biochemical marker of BPAN.•Gradually decreasing severity of epilepsy in some BPAN patients.