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Insights from long term follow-up of a girl with adrenal insufficiency and sphingosine-1-phosphate lyase deficiency

Maharaj, Avinaash; Güran, Tülay; Buonocore, Federica; Achermann, John C; Metherell, Louise; Prasad, Rathi; Çetinkaya, Semra; (2022) Insights from long term follow-up of a girl with adrenal insufficiency and sphingosine-1-phosphate lyase deficiency. Journal of the Endocrine Society 10.1210/jendso/bvac020. (In press). Green open access

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Abstract

Introduction Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multi-systemic disorder which, in the main, incorporates steroid resistant nephrotic syndrome and primary adrenal insufficiency (PAI). Case Presentation We present a young girl with a novel homozygous variant in SGPL1; p.D350G, with PAI in the absence of nephrotic syndrome. In the course of 15 years of follow up she has further developed primary hypothyroidism and whilst she has progressed through puberty appropriately, ovarian calcifications were noted on imaging. The p.D350G variant results in reduced protein expression of SGPL1. We demonstrate that CRISPR engineered knockout of SGPL1 in human adrenocortical (H295R) cells abrogates cortisol production. Furthermore, whilst wild-type SGPL1 is able to rescue cortisol production in this in vitro model of adrenal disease, this is not observed with the p.D350G mutant. Conclusion SGPL1 deficiency should be considered in the differential diagnosis of PAI with close attention paid to evolving disease on follow up.

Type: Article
Title: Insights from long term follow-up of a girl with adrenal insufficiency and sphingosine-1-phosphate lyase deficiency
Open access status: An open access version is available from UCL Discovery
DOI: 10.1210/jendso/bvac020
Publisher version: http://doi.org/10.1210/jendso/bvac020
Language: English
Additional information: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third-party material in this article are included in the Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Genetics and Genomic Medicine Dept
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
URI: https://discovery.ucl.ac.uk/id/eprint/10144114
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