Insights From Long-term Follow-up of a Girl With Adrenal Insufficiency and Sphingosine-1-Phosphate Lyase Deficiency.
J Endocr Soc
; 6(5): bvac020, 2022 May 01.
Article
em En
| MEDLINE
| ID: mdl-35308304
ABSTRACT
Introduction:
Sphingosine-1-phosphate lyase (SGPL1) insufficiency syndrome (SPLIS) is a multisystemic 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 while 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, while 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.
Texto completo:
1
Bases de dados:
MEDLINE
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
J Endocr Soc
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Reino Unido