{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T15:28:23Z","timestamp":1790609303436,"version":"4.1.0"},"reference-count":51,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["ec.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p>\n                    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\n                    <jats:italic>SGPL1<\/jats:italic>\n                    variants and assess for genotype\u2013phenotype 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,\n                    <jats:italic>SGPL1<\/jats:italic>\n                    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\n                    <jats:italic>SGPL1<\/jats:italic>\n                    deficiency on growth, and pubertal development, limited by the early and high mortality rate (approximately 50%). There is no clear genotype\u2013phenotype 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.\n                    <jats:bold\/>\n                    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.\n                  <\/jats:p>","DOI":"10.1530\/ec-22-0250","type":"journal-article","created":{"date-parts":[[2022,6,28]],"date-time":"2022-06-28T09:24:44Z","timestamp":1656408284000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-10","source":"Crossref","is-referenced-by-count":11,"title":["A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review"],"prefix":"10.1530","volume":"11","author":[{"given":"Avinaash","family":"Maharaj","sequence":"first","affiliation":[{"name":"Centre for Endocrinology, John Vane Science Centre, Queen Mary University of London, London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth","family":"Kwong","sequence":"additional","affiliation":[{"name":"Centre for Endocrinology, John Vane Science Centre, Queen Mary University of London, London, 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(https:\/\/doi.org\/10.1210\/clinem\/dgac016)10.1210\/clinem\/dgac016"},{"key":"bib21","series-title":"Journal of the Endocrine Society","article-title":"Insights from long term follow-up of a girl with adrenal insufficiency and sphingosine-1-phosphate lyase deficiency","volume":"6","author":"Maharaj","year":"2022","unstructured":"Maharaj AG\u00fcran TBuonocore FAchermann JCMetherell LPrasad R\u00c7etinkaya S. Insights from long term follow-up of a girl with adrenal insufficiency and sphingosine-1-phosphate lyase deficiency. Journal of the Endocrine Society20226 bvac020. (https:\/\/doi.org\/10.1210\/jendso\/bvac020)34258490"},{"key":"bib22","series-title":"Radiology","article-title":"Radiographic findings in Wolman\u2019s disease","volume":"124","author":"Harrison","year":"1977","unstructured":"Harrison RBFrancke P. Radiographic findings in Wolman\u2019s disease. Radiology1977124 188. (https:\/\/doi.org\/10.1148\/124.1.188)"},{"key":"bib23","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1210\/jcem-50-1-52","article-title":"Significance of thyrotropin excess in untreated primary adrenal insufficiency","volume":"50","author":"Topliss","year":"1980","unstructured":"Topliss DJWhite ELStockigt JR. Significance of thyrotropin excess in untreated primary adrenal insufficiency. Journal of Clinical Endocrinology and Metabolism19805052\u201356. (https:\/\/doi.org\/10.1210\/jcem-50-1-52)10.1210\/jcem-50-1-52"},{"key":"bib24","series-title":"American Journal of Nephrology","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1159\/000166587","article-title":"Thyroid function in patients with nephrotic syndrome and normal renal function","volume":"2","author":"Feinstein","year":"1982","unstructured":"Feinstein EIKaptein EMNicoloff JTMassry SG. Thyroid function in patients with nephrotic syndrome and normal renal function. American Journal of Nephrology1982270\u201376. (https:\/\/doi.org\/10.1159\/000166587)10.1159\/00016658717196738"},{"key":"bib25","series-title":"GeneReviews","article-title":"Sphingosine phosphate lyase insufficiency syndrome","author":"Weaver","year":"1993","unstructured":"Weaver KNSullivan BHildebrandt FStrober JCooper MPrasad RSaba J. Sphingosine phosphate lyase insufficiency syndrome. In GeneReviews. Eds AdamMPArdingerHHPagonRAWallaceSEBeanLJMirzaaGAmemiyaA. Seattle, WA, USA: University of Washington, 1993. (available at: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK562988\/)16183668"},{"key":"bib26","series-title":"Journal of the Endocrine Society","article-title":"Genetic analysis of pediatric primary adrenal insufficiency of unknown etiology: 25 years\u2019 experience in the UK","volume":"5","author":"Buonocore","year":"2021","unstructured":"Buonocore FMaharaj AQamar YKoehler KSuntharalingham JPChan LFFerraz-de-Souza BHughes CRLin LPrasad RGenetic analysis of pediatric primary adrenal insufficiency of unknown etiology: 25 years\u2019 experience in the UK. Journal of the Endocrine Society20215 bvab086. (https:\/\/doi.org\/10.1210\/jendso\/bvab086)8145764"},{"key":"bib27","series-title":"Journal of Clinical Endocrinology and Metabolism","first-page":"1511","article-title":"Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein","volume":"82","author":"Bose","year":"1997","unstructured":"Bose HSPescovitz OHMiller WL. Spontaneous feminization in a 46,XX female patient with congenital lipoid adrenal hyperplasia due to a homozygous frameshift mutation in the steroidogenic acute regulatory protein. Journal of Clinical Endocrinology and Metabolism1997821511\u20131515. (https:\/\/doi.org\/10.1210\/jcem.82.5.3962)1922026"},{"key":"bib28","series-title":"Journal of Clinical Investigation","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1172\/JCI119284","article-title":"Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene","volume":"99","author":"Fujieda","year":"1997","unstructured":"Fujieda KTajima TNakae JSageshima STachibana KSuwa SSugawara TStrauss JF. Spontaneous puberty in 46,XX subjects with congenital lipoid adrenal hyperplasia. Ovarian steroidogenesis is spared to some extent despite inactivating mutations in the steroidogenic acute regulatory protein (StAR) gene. Journal of Clinical Investigation1997991265\u20131271. (https:\/\/doi.org\/10.1172\/JCI119284)10.1172\/JCI11928427716753"},{"key":"bib29","series-title":"JCI Insight","article-title":"Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome","volume":"6","author":"Zhao","year":"2021","unstructured":"Zhao PTassew GBLee JYOskouian BMu\u00f1oz DPHodgin JBWatson GLTang FWang JYLuo JEfficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome. JCI Insight20216 e145936. (https:\/\/doi.org\/10.1172\/jci.insight.145936)32682944"},{"key":"bib30","series-title":"Nature Genetics","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1038\/ng1922","article-title":"PDGF signaling specificity is mediated through multiple immediate early genes","volume":"39","author":"Schmahl","year":"2007","unstructured":"Schmahl JRaymond CSSoriano P. PDGF signaling specificity is mediated through multiple immediate early genes. Nature Genetics20073952\u201360. 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(https:\/\/doi.org\/10.1016\/j.mce.2006.12.016)"},{"key":"bib34","series-title":"Cellular Signalling","doi-asserted-by":"publisher","first-page":"827","DOI":"10.1016\/j.cellsig.2004.11.022","article-title":"Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells: endogenous sphingosine-1-phosphate as a modulator of the calcium response","volume":"17","author":"Blom","year":"2005","unstructured":"Blom TSlotte JPPitson SMT\u00f6rnquist K. Enhancement of intracellular sphingosine-1-phosphate production by inositol 1,4,5-trisphosphate-evoked calcium mobilisation in HEK-293 cells: endogenous sphingosine-1-phosphate as a modulator of the calcium response. Cellular Signalling200517827\u2013836. (https:\/\/doi.org\/10.1016\/j.cellsig.2004.11.022)10.1016\/j.cellsig.2004.11.022"},{"key":"bib35","series-title":"FASEB Journal","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1096\/fj.01-0809com","article-title":"N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization","volume":"16","author":"Kohno","year":"2002","unstructured":"Kohno TWada AIgarashi Y. N-glycans of sphingosine 1-phosphate receptor Edg-1 regulate ligand-induced receptor internalization. FASEB Journal200216983\u2013992. (https:\/\/doi.org\/10.1096\/fj.01-0809com)10.1096\/fj.01-0809com"},{"key":"bib36","series-title":"Molecular Biology of the Cell","doi-asserted-by":"publisher","first-page":"1179","DOI":"10.1091\/mbc.10.4.1179","article-title":"Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1","volume":"10","author":"Liu","year":"1999","unstructured":"Liu CHThangada SLee MJVan Brocklyn JRSpiegel SHla T. Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1. Molecular Biology of the Cell1999101179\u20131190. (https:\/\/doi.org\/10.1091\/mbc.10.4.1179)10.1091\/mbc.10.4.1179"},{"key":"bib37","series-title":"Journal of Experimental Medicine","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1084\/jem.20041509","article-title":"Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit","volume":"201","author":"Lo","year":"2005","unstructured":"Lo CGXu YProia RLCyster JG. Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit. Journal of Experimental Medicine2005201291\u2013301. (https:\/\/doi.org\/10.1084\/jem.20041509)10.1084\/jem.20041509"},{"key":"bib38","series-title":"Endocrinology","doi-asserted-by":"publisher","first-page":"1464","DOI":"10.1210\/en.2003-1432","article-title":"Sphingolipid-cholesterol domains (lipid rafts) in normal human and dog thyroid follicular cells are not involved in thyrotropin receptor signaling","volume":"145","author":"Costa","year":"2004","unstructured":"Costa MJSong YMacours PMassart CMany MCCostagliola SDumont JEVan Sande JVanvooren V. Sphingolipid-cholesterol domains (lipid rafts) in normal human and dog thyroid follicular cells are not involved in thyrotropin receptor signaling. Endocrinology20041451464\u20131472. (https:\/\/doi.org\/10.1210\/en.2003-1432)10.1210\/en.2003-1432"},{"key":"bib39","series-title":"American Journal of Physiology: Lung Cellular and Molecular Physiology","first-page":"L351","article-title":"Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity","volume":"290","author":"Sparkman","year":"2006","unstructured":"Sparkman LChandru HBoggaram V. Ceramide decreases surfactant protein B gene expression via downregulation of TTF-1 DNA binding activity. American Journal of Physiology: Lung Cellular and Molecular Physiology2006290L351\u2013L358. (https:\/\/doi.org\/10.1152\/ajplung.00275.2005)"},{"key":"bib40","series-title":"Molecular Endocrinology","first-page":"1589","article-title":"Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene","volume":"7","author":"Civitareale","year":"1993","unstructured":"Civitareale DCastelli MPFalasca PSaiardi A. Thyroid transcription factor 1 activates the promoter of the thyrotropin receptor gene. Molecular Endocrinology199371589\u20131595. (https:\/\/doi.org\/10.1210\/mend.7.12.8145764)"},{"key":"bib41","series-title":"EMBO Journal","doi-asserted-by":"publisher","first-page":"2537","DOI":"10.1002\/j.1460-2075.1989.tb08391.x","article-title":"A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter","volume":"8","author":"Civitareale","year":"1989","unstructured":"Civitareale DLonigro RSinclair AJDi Lauro R. A thyroid-specific nuclear protein essential for tissue-specific expression of the thyroglobulin promoter. EMBO Journal198982537\u20132542. (https:\/\/doi.org\/10.1002\/j.1460-2075.1989.tb08391.x)10.1002\/j.1460-2075.1989.tb08391.x"},{"key":"bib42","series-title":"Molecular and Cellular Biology","doi-asserted-by":"publisher","first-page":"10171","DOI":"10.1128\/MCB.25.22.10171-10182.2005","article-title":"Pendrin is a novel in vivo downstream target gene of the TTF-1\/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells","volume":"25","author":"Dentice","year":"2005","unstructured":"Dentice MLuongo CElefante AAmbrosio RSalzano SZannini MNitsch RDi Lauro RRossi GFenzi GPendrin is a novel in vivo downstream target gene of the TTF-1\/Nkx-2.1 homeodomain transcription factor in differentiated thyroid cells. Molecular and Cellular Biology20052510171\u201310182. (https:\/\/doi.org\/10.1128\/MCB.25.22.10171-10182.2005)10.1128\/MCB.25.22.10171-10182.2005"},{"key":"bib43","series-title":"Molecular and Cellular Biology","first-page":"4927","article-title":"Thyroid-specific enhancer-binding protein (T\/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF-1","volume":"11","author":"Mizuno","year":"1991","unstructured":"Mizuno KGonzalez FJKimura S. Thyroid-specific enhancer-binding protein (T\/EBP): cDNA cloning, functional characterization, and structural identity with thyroid transcription factor TTF-1. Molecular and Cellular Biology1991114927\u20134933. 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Mitochondrial disease and endocrine dysfunction. Nature Reviews: Endocrinology20171392\u2013104. (https:\/\/doi.org\/10.1038\/nrendo.2016.151)"},{"key":"bib47","series-title":"Journal of Steroid Biochemistry and Molecular Biology","article-title":"Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction","volume":"202","author":"Maharaj","year":"2020","unstructured":"Maharaj AWilliams JBradshaw TG\u00fcran TBraslavsky DCasas JChan LFMetherell LAPrasad R. Sphingosine-1-phosphate lyase (SGPL1) deficiency is associated with mitochondrial dysfunction. Journal of Steroid Biochemistry and Molecular Biology2020202 105730. (https:\/\/doi.org\/10.1016\/j.jsbmb.2020.105730)"},{"key":"bib48","series-title":"Orphanet Journal of Rare Diseases","article-title":"Endocrine manifestations related to inherited metabolic diseases in adults","volume":"7","author":"Vantyghem","year":"2012","unstructured":"Vantyghem MCDobbelaere DMention KWemeau JLSaudubray JMDouillard C. Endocrine manifestations related to inherited metabolic diseases in adults. Orphanet Journal of Rare Diseases20127 11. (https:\/\/doi.org\/10.1186\/1750-1172-7-11)"},{"key":"bib49","series-title":"Journal of Inherited Metabolic Disease","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1007\/s10545-005-0003-3","article-title":"High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease","volume":"28","author":"Hauser","year":"2005","unstructured":"Hauser ACGessl ALorenz MVoigtl\u00e4nder TF\u00f6dinger MSunder-Plassmann G. High prevalence of subclinical hypothyroidism in patients with Anderson-Fabry disease. Journal of Inherited Metabolic Disease200528715\u2013722. (https:\/\/doi.org\/10.1007\/s10545-005-0003-3)10.1007\/s10545-005-0003-3"},{"key":"bib50","series-title":"Journal of Clinical Endocrinology and Metabolism","doi-asserted-by":"publisher","first-page":"4319","DOI":"10.1210\/jc.2006-0858","article-title":"Endocrine dysfunction in patients with Fabry disease","volume":"91","author":"Faggiano","year":"2006","unstructured":"Faggiano APisani AMilone FGaccione MFilippella MSantoro AVallone GTortora FSabbatini MSpinelli LEndocrine dysfunction in patients with Fabry disease. Journal of Clinical Endocrinology and Metabolism2006914319\u20134325. (https:\/\/doi.org\/10.1210\/jc.2006-0858)10.1210\/jc.2006-0858"},{"key":"bib51","series-title":"European Heart Journal","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1093\/eurheartj\/ehp387","article-title":"Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease","volume":"31","author":"Brakch","year":"2010","unstructured":"Brakch NDormond OBekri SGolshayan DCorrevon MMazzolai LSteinmann BBarbey F. Evidence for a role of sphingosine-1 phosphate in cardiovascular remodelling in Fabry disease. European Heart Journal20103167\u201376. 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