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Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1.

ABSTRACT: Little is known about the molecular pathogenesis of congenital nephrotic syndrome in association with primary adrenal insufficiency. Most recently, three groups found concurrently the underlying genetic defect in the gene sphingosine-1-phosphate lyase 1 (SGPL1) and called the disease nephrotic syndrome type 14 (NPHS14). In this report we have performed whole-exome sequencing and identified a new homozygous variant in SGPL1, p.Arg340Trp, in a girl with nephrotic syndrome and Addison's disease. Her brother died previously with the same phenotype and hyperpigmentation of the skin. We reviewed the reported cases and concluded that NPHS14 is a clinically recognizable syndrome. The discovery of this syndrome may contribute to the diagnosis and description of additional patients who could benefit from treatment, genetic counseling and screening for related comorbidities. Until now, patients with congenital nephrotic syndrome associated with primary adrenal insufficiency have been treated as having two different diseases; however, the treatment for patients with NPHS14 should be unique, possibly targeting the sphingolipid metabolism.

SUBMITTER: Linhares ND

PROVIDER: S-EPMC6070023 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1.

Linhares Natália Duarte ND Arantes Rodrigo Rezende RR Araujo Stanley Almeida SA Pena Sergio D J SDJ

Clinical kidney journal 20171113 4

Little is known about the molecular pathogenesis of congenital nephrotic syndrome in association with primary adrenal insufficiency. Most recently, three groups found concurrently the underlying genetic defect in the gene sphingosine-1-phosphate lyase 1 (SGPL1) and called the disease nephrotic syndrome type 14 (NPHS14). In this report we have performed whole-exome sequencing and identified a new homozygous variant in SGPL1, p.Arg340Trp, in a girl with nephrotic syndrome and Addison ...[more]

PMID: 30090628

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Project description:ImportancePediatric pseudotumor cerebri syndrome pathophysiology is complex and not well delineated. Therefore, it is important to identify potential contributors or targets underlying the primary pathogenesis for its development.ObjectiveTo report cases highlighting the association of pediatric pseudotumor cerebri syndrome with adrenal insufficiency.Design, setting, and participantsThis noncontrolled, observational case series included pediatric patients diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency at an urban academic children's hospital in Houston, Texas, from June 2015 to October 2019.Main outcomes and measuresMonitoring optic nerve edema by clinical examination, fundus photography, and optical coherence topography images of the optic nerve.ResultsData were collected from 5 pediatric patients (age range, 5-10 years) diagnosed with pseudotumor cerebri syndrome and adrenal insufficiency. One was a girl; all were White and prepubertal. Three patients had unrecognized glucocorticoid exposure. All patients had bilateral optic nerve edema that was initially treated with acetazolamide or topiramate, but cortisol functional testing by either 8 am cortisol or cosyntropin stimulation tests revealed a diagnosis of central adrenal insufficiency. Treatment with physiological doses of hydrocortisone resulted in resolution of optic nerve edema and clinical symptoms of pseudotumor cerebri syndrome, as well as a shorter time receiving medical therapy.Conclusions and relevanceIn this case series, adrenal insufficiency was associated with both primary and secondary prepubertal pediatric pseudotumor cerebri syndrome. As a potential target specific to causative mechanism, physiologic hydrocortisone therapy resolved the condition. To date, there remains a global unawareness among clinicians about the suppressive outcome that glucocorticoids may have on the developing hypothalamic-pituitary-adrenal axis, resulting in adrenal insufficiency and so-called episodic pseudotumor cerebri syndrome in young children. Ophthalmologists and pediatric subspecialists should implement cortisol testing via either 8 am cortisol or cosyntropin stimulation tests at initial evaluation of all children with pseudotumor cerebri syndrome and risk factors for adrenal insufficiency, no predisposing causes, or nonresponse to conventional treatment. Further management and treatment should be in combination with ophthalmology and endocrine services.

Dataset Information

Nephrotic syndrome and adrenal insufficiency caused by a variant in SGPL1.

Publications

Nephrotic syndrome and adrenal insufficiency caused by a variant in <i>SGPL1</i>.

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