LETTERS TO THE EDITOR
Year : 2022 | Volume
: 25 | Issue : 2 | Page : 304-
Only pathogenic SURF-1 variants cause leigh syndrome
Klinik Landstrasse, Messerli Institute, Postfach 20, 1180 Vienna, Austria
Postfach 20, 1180 Vienna
|How to cite this article:|
Finsterer J. Only pathogenic SURF-1 variants cause leigh syndrome.Ann Indian Acad Neurol 2022;25:304-304
|How to cite this URL:|
Finsterer J. Only pathogenic SURF-1 variants cause leigh syndrome. Ann Indian Acad Neurol [serial online] 2022 [cited 2022 Oct 3 ];25:304-304
Available from: https://www.annalsofian.org/text.asp?2022/25/2/304/328998
To the Editor,
With interest, we read the article by Panda et al. dated 3/2021 about a 3-month-old male with Leigh syndrome due to the intronic variants (intron-8 [c.833+1G>A] and intron-4 [c.324-11T>G]) in SURF1. The patient manifested phenotypically with febrile seizures, generalized hypotonia, lactic acidosis, and bilateral basal ganglia lesions. The study is appealing but raises comments and concerns.
The pathogenicity of the variant is unproven. In-silico prediction is insufficient to predict pathogenicity. We should be informed if the variant occurred sporadically or was inherited. Thus, investigations of first-degree relatives are required. It should be clarified if the variant segregated with the phenotype within the family. Thus, it is crucial to know if other first-degree relatives were clinically or subclinically affected as well and if other family members, phenotypically affected or not, carried the variant as well.
The pathogenicity should be confirmed on functional tests to assess if the variant truly resulted in a reduced expression of SURF1 and reduced or absent activity of SURF1. SURF1 is a component of the mitochondrial translation regulation assembly intermediate of cytochrome-c oxidase complex (MITRAC complex), which is involved in the regulation of the cytochrome-c oxidase assembly. If SURF1 is deficient or reduced in activity, complex-IV deficiency ensues. Accordingly, biochemical studies should be carried out to demonstrate that the SURF1 variant truly caused complex-IV deficiency. We should know if the biochemical investigations of a clinically affected tissue truly demonstrated reduced activity of this assembly factor.
The patient was treated not only with levetiracetam but also with cofactors and vitamins. We should be told which particular compounds were given and if they exhibited a beneficial effect or not. We should also be informed if epileptiform discharges on electroencephalography (EEG) disappeared upon the administration of levetiracetam.
Since SURF1 variants manifest with a homogeneous clinical and biochemical phenotype, we should be told if the index patient or any of his affected first-degree relatives expressed typical features of the phenotype other than epilepsy, hypotonia, lactic acidosis, and symmetric basal ganglia or brainstem lesions. These other phenotypic features include developmental delay, optic atrophy, failure to thrive, dysphagia, respiratory dysfunction, impaired thermoregulation, facial dysmorphism, hirsutism, thiamine deficiency, hypopigmentation, and extrapyramidal features, such as ataxia, dyskinesia, akinesia, and dystonia.,
Overall, the interesting report has several limitations, which challenge the results and their interpretation. There is a need to prove the pathogenicity of the SURF1 variants, to investigate clinically and genetically the first-degree relatives, and to provide follow-up data.
JF: design, literature search, discussion, first draft, critical comments, final approval
Statement of ethics
Was in accordance of ethical guidelines.
The study was approved by the institutional review board.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
|1||Panda PK, Sharawat IK, Sharma V, Sherwani P. Leigh syndrome and SURF1 gene presenting with febrile seizure. Ann Indian Acad Neurol 2021;24:251-2.|
|2||Kose M, Canda E, Kagnici M, Aykut A, Adebali O, Durmaz A, et al. SURF1 related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkey. Mol Genet Metab Rep 2020;25:100657.|
|3||Lee IC, El-Hattab AW, Wang J, Li FY, Weng SW, Craigen WJ, et al. SURF1-associated Leigh syndrome: A case series and novel mutations. Hum Mutat 2012;33:1192-200.|
|4||Baskaran D, Hussain N. Facial dysmorphism, hirsutism, and failure to thrive as manifestation of leigh syndrome in a child with SURF1 mutation. J Pediatr Neurosci 2020;15:108-10.|