A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease

Alexandra Astner-Rohracher; Matthias Mauritz; Markus Leitinger; Fabio Rossini; Gudrun Kalss; Caroline Neuray; Elisabeth Retter; Saskia B Wortmann; Melanie T Achleitner; Johannes A Mayr; Eugen Trinka

doi:10.3389/fneur.2022.1063733

A case report: New-onset refractory status epilepticus in a patient with FASTKD2-related mitochondrial disease

Front Neurol. 2023 Jan 11:13:1063733. doi: 10.3389/fneur.2022.1063733. eCollection 2022.

Authors

Alexandra Astner-Rohracher^{1

2}, Matthias Mauritz^{1

2}, Markus Leitinger^{1

2}, Fabio Rossini^{1

2}, Gudrun Kalss^{1

2}, Caroline Neuray¹, Elisabeth Retter³, Saskia B Wortmann^{4

5}, Melanie T Achleitner⁴, Johannes A Mayr⁴, Eugen Trinka^{1

2

6

7}

Affiliations

¹ Department of Neurology, Neurocritical Care, and Neurorehabilitation, Christian Doppler University Hospital, Centre for Cognitive Neuroscience, Paracelsus Medical University, Salzburg, Austria.
² Neuroscience Institute, Christian Doppler University Hospital, Centre for Cognitive Neuroscience Paracelsus Medical University Hospital, Salzburg, Austria.
³ Neurology Practice, Tamsweg, Austria.
⁴ University Children's Hospital, Paracelsus Medical University, Salzburg, Austria.
⁵ Department of Pediatrics, Radboud Center for Mitochondrial Medicine, Amalia Children's Hospital, Radboudumc, Nijmegen, Netherlands.
⁶ Karl Landsteiner Institute for Neurorehabilitation and Space Neurology, Salzburg, Austria.
⁷ Department of Public Health, Health Services Research and Health Technology Assessment, UMIT-University for Health Sciences, Medical Informatics and Technology, Hall in Tirol, Austria.

Abstract

Objectives: New-onset refractory status epilepticus (NORSE) is associated with high morbidity and mortality. Despite extensive work-up, the underlying etiology remains unknown in 50% of affected individuals. Mitochondrial disorders represent rare causes of NORSE. Biallelic variants in FASTKD2 were reported as a cause of infantile encephalomyopathy with refractory epilepsy.

Case description: In the study, we report a previously healthy 14-year-old with a new, homozygous FASTKD2 variant presenting with NORSE. Following a seizure-free period of 7 years, he experienced another super-refractory SE and subsequently developed drug-resistant focal epilepsy, mild myopathy, optic atrophy, and discrete psychomotor slowing. Structural MRI at the time of NORSE showed right temporo-parieto-occipital FLAIR hyperintensity and diffusion restriction, with extensive right hemispheric atrophy at the age of 22 years. Whole-exome sequencing revealed a novel homozygous loss of function variant [c.(1072C>T);(1072C>T)] [p.(Arg358Ter);(Arg358Ter)] in FASTKD2 (NM_001136193), resulting in a premature termination codon in the protein-coding region and loss of function of FASTKD2. Oxidative phosphorylation (OXPHOS) in muscle and skin fibroblasts was unremarkable.

Conclusion: This is the first case of a normally developed adolescent with a new homozygous loss of function variant in FASTKD2, manifesting with NORSE. The phenotypical spectrum of FASTKD2-related mitochondrial disease is heterogeneous, ranging from recurrent status epilepticus and refractory focal epilepsy in an adolescent with normal cognitive development to severe forms of infantile mitochondrial encephalopathy. Although mitochondrial diseases are rare causes of NORSE, clinical features such as young age at onset and multi-system involvement should trigger genetic testing. Early diagnosis is essential for counseling and treatment considerations.

Keywords: FASTKD2 mutation; drug-resistant epilepsy; genetic epilepsies; mitochondrial disease; new-onset refractory status epilepticus (NORSE).

Publication types

Case Reports