Pediatric neurology · 2025
Case Report of Pediatric HPCA-Associated Dystonia: Analysis of Ca2+ and K+ Channel Dynamics and Experience With Pallidal Deep Brain Stimulation.
СтатьяКлинический случайНазвание и аннотация: Перевод в очереди
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Nou-Fontanet Laia, Ousingsawat Jiraporn, Aziz Majid, Maroofian Reza, Karimiani Ehsan Ghayoor, Fernández-López Anna, Candela-Cantó Santiago, Rumià Jordi, Dominguez Ana Maria, Schreiber Rainer, Kunzelmann Karl, Ortigoza-Escobar Juan Dario
Аннотация
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.
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.