Maharaj, Avinaash;
Kwong, Ruth;
Williams, Jack;
Smith, Christopher;
Storr, Helen;
Krone, Ruth;
Braslavsky, Debora;
... Prasad, Rathi; + view all
(2022)
A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.
Endocrine Connections
, 11
(8)
, Article e220250. 10.1530/EC-22-0250.
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Abstract
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is an autosomal recessive multi-system disorder, which mainly incorporates steroid-resistant nephrotic syndrome and primary adrenal insufficiency. Other variable endocrine manifestations are described. In this study, we aimed to comprehensively annotate the endocrinopathies associated with pathogenic SGPL1 variants and assess for genotype-phenotype correlations by retrospectively reviewing the reports of endocrine disease within our patient cohort and all published cases in the wider literature up to February 2022. Glucocorticoid insufficiency in early childhood is the most common endocrine manifestation affecting 64% of the 50 patients reported with SPLIS, and a third of these individuals have additional mineralocorticoid deficiency. While most individuals also have nephrotic syndrome, SGPL1 variants also account for isolated adrenal insufficiency at presentation. Primary gonadal insufficiency, manifesting with microphallus and cryptorchidism, is reported in less than one-third of affected boys, all with concomitant adrenal disease. Mild primary hypothyroidism affects approximately a third of patients. There is paucity of data on the impact of SGPL1 deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype-phenotype correlation overall in the syndrome, with variable disease penetrance within individual kindreds. However, with regards to endocrine phenotype, the most prevalent disease variant p.R222Q (affecting 22%) is most consistently associated with isolated glucocorticoid deficiency. To conclude, SPLIS is associated with significant multiple endocrine disorders. While endocrinopathy in the syndrome generally presents in infancy, late-onset disease also occurs. Screening for these is therefore warranted both at diagnosis and through follow-up.
| Type: | Article |
|---|---|
| Title: | A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1530/EC-22-0250 |
| Publisher version: | https://doi.org/10.1530/EC-22-0250 |
| Language: | English |
| Additional information: | © 2022 The authors Published by Bioscientifica Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | SGPL1, primary adrenal insufficiency, primary gonadal insufficiency, primary hypothyroidism, sphingolipids, sphingosine-1-phosphate lyase |
| 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/10153531 |
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