Nou-Fontanet, Laia and Ousingsawat, Jiraporn and Aziz, Majid and Maroofian, Reza and Karimiani, Ehsan Ghayoor and Fernandez-Lopez, Anna and Candela-Canto, Santiago and Rumia, Jordi and Dominguez, Ana Maria and Schreiber, Rainer and Kunzelmann, Karl and Ortigoza-Escobar, Juan Dario (2025) Case Report of Pediatric HPCA-Associated Dystonia: Analysis of Ca2+and K+ Channel Dynamics and Experience With Pallidal Deep Brain Stimulation. PEDIATRIC NEUROLOGY, 172. pp. 46-52. ISSN 0887-8994, 1873-5150
Full text not available from this repository. (Request a copy)Abstract
Background: Biallelic pathogenic variants in the HPCA gene cause HPCA-associated dystonia (DYT-HPCA), a rare autosomal recessive disorder characterized by generalized dystonia and complex motor symptoms. HPCA encodes hippocalcin, a Ca2+ sensor that modulates neuronal activity through K+ channel activation. Here, we describe the clinical and molecular features of two children with novel HPCA variants and assess the impact of deep brain stimulation (DBS) (globus pallidus internus [Gpi]-DBS) on their movement disorders. Methods: Two sisters with HPCA variants (c.91_98del/p.Tyr31Leufs14) were evaluated. Functional studies in fibroblasts from one sister and a previously reported case (HPCA c.49C > T/p.Arg17) analyzed Ca2+ signaling and K+ channel activity. One sister underwent GPi-DBS, with therapeutic response monitored using the Burke-Fahn-Marsden Dystonia Rating Scale and the Abnormal Involuntary Movement Scale. Results: GPi-DBS improved dystonia and chorea in one patient, reducing Burke-Fahn-Marsden scores by 51%. Fibroblast analyses showed no differences in Ca2+ signaling or K+ channel activation between cells expressing mutated HPCA and wild-type HPCA. Conclusions: Preliminary evidence from a single pediatric patient suggests that GPi-DBS may be effective for DYT-HPCA in children, but the molecular mechanisms remain unclear, highlighting the need for further research. (c) 2025 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIPPOCALCIN; ACTIVATION; Dystonia; HPCA; Deep brain stimulation; Hippocalcin; Ca2+ signaling; K+ channels |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Physiologie Biology, Preclinical Medicine > Institut für Physiologie > Prof. Dr. Karl Kunzelmann |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Apr 2026 09:24 |
| Last Modified: | 17 Apr 2026 09:24 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67708 |
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