With interest we read the article by Lonardi et al. about a 2 years old child with sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) who developed complete, unilateral oculomotor palsy three weeks after resolution of a mild SARS-CoV-2 infection [1]. Oculomotor palsy was interpreted as a  complication of COVID-19 [1]. The study is appealing but raises comments and concerns.

SPLIS is phenotypically not only characterised by steroid-resistant nephrotic syndrome, primary adrenal insufficiency (with or without mineralocorticoid deficiency), testicular insufficiency, hypothyroidism, ichthyosis, lymphopenia/immunodeficiency, developmental delay, and peripheral motor and sensory neuropathy], but also by cranial nerve deficits [2]. Since oculomotor palsy is a rare complication of COVID-19, it is more likely that oculomotor palsy was in fact a manifestation of the underlying genetic defect, which became apparent  during the viral infection. Arguments in favour of the metabolic cause of oculomotor palsy are that steroids were hardly effective and that CSF investigations were normal. 

Another pathophysiological explanation for oculomotor palsy could be hypothyroidism. From hypothyroidism it is known that it can be occasionally complicated by oculomotor palsy [3]. Thus, we should be informed if the index patient manifested with hypothyroidism and if oculomotor palsy resolved with appropriate treatment of hypothyroidism.   

The patient was diagnosed with SARS-CoV-2 associated transverse myelitis but CSF investigations were normal. How to explain this discrepancy? We should know how transverse myelitis was treated and if steroids were beneficial for transverse myelitis.   

SPLIS is due to mutations in SGPL1. Thus, we should be informed which SGPL1 variant was responsible for the phenotype of the index patient. We also should be informed if the variant occurred sporadically or was inherited from either parent.

Overall, the report has some limitations which challenge the results and their interpretation.  Addressing our concerns could strengthen the conclusions.