SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency.

This is a pre-copyedited, author-produced version of an article accepted for publication in Journal of Clinical Endocrinology & Metabolism following peer review. The version of record Settas, N., et al. (2018). "SGPL1 Deficiency: A Rare Cause of Primary Adrenal Insufficiency." The Journal of Clinical Endocrinology & Metabolism: jc.2018-02238-jc.02018-02238. is available online at: https://doi.org/10.1210/jc.2018-02238Context Multiple autosomal recessive genes have been etiologically linked to Primary Adrenal Insufficiency (PAI). Recently, SGPL1 gene mutations were recognized as causes of steroid-resistant nephrotic syndrome type 14 (NPHS14), a sphingolipidosis with multisystemic manifestations including PAI. Interestingly, this is the only monogenetic form of nephrotic syndrome (NS) and the sole sphingolipidosis causing adrenal disease. Objective To understand if SGPL1 mutations are involved in the pathogenesis of PAI in patients who do not exhibit NS. Methods Sequencing of the SGPL1 gene in 21 patients with familial glucocorticoid disease or triple A syndrome. Results We identified two missense SGPL1 variants in four patients, two being first-cousins. We describe in detail the proband, a boy born to Saudi Arabian consanguineous parents with a homozygous c.665G>A, p.R222Q SGPL1 variant. The patient presented with hypoglycemia and seizures at age two years and was ultimately diagnosed with PAI (isolated glucocorticoid deficiency). A brain MRI showed abnormalities in the basal ganglia consistent with a degenerative process albeit the patient had no neurological symptoms. Conclusions New genetic causes of PAI continue to be identified. We suggest that screening for SGPL1 mutations should not be reserved only for patients with nephrotic syndrome but may also include patients with PAI that lack other clinical manifestations of NPHS14 since, in certain cases, kidney disease and accompanying features might develop later on. Timely diagnosis of this specific sphingolipidosis, while the kidneys still function normally, can lead to prompt initiation of therapy and improve outcome especially, if a targeted NPHS14-treatment is available in the future.Eunice Kennedy Shriver National Institute of Child Health & Human Development, National Institutes of Health (project number Z1A HD008920)National Institute of Child Health and Human Development http://dx.doi.org/10.13039/100000071, Z1A HD008920, Constantine A. Strataki

Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting.

syndrome affects 25–50 per 100,000 females and can involve multiple organs through all stages of life, necessitating multidisciplinary approach to care. Previous guidelines have highlighted this, but numerous important advances have been noted recently. These advances cover all specialty fields involved in the care of girls and women with TS. This paper is based on an international effort that started with exploratory meetings in 2014 in both Europe and the USA, and culminated with a Consensus Meeting held in Cincinnati, Ohio, USA in July 2016. Prior to this meeting, five groups each addressed important areas in TS care: 1) diagnostic and genetic issues, 2) growth and development during childhood and adolescence, 3) congenital and acquired cardiovascular disease, 4) transition and adult care, and 5) other comorbidities and neurocognitive issues. These groups produced proposals for the present guidelines. Additionally, four pertinent questions were submitted for formal GRADE (Grading of Recommendations, Assessment, Development and Evaluation) evaluation with a separate systematic review of the literature. These four questions related to the efficacy and most optimal treatment of short stature, infertility, hypertension, and hormonal replacement therapy. The guidelines project was initiated by the European Society of Endocrinology and the Pediatric Endocrine Society, in collaboration with the European Society for Paediatric Endocrinology, the Endocrine Society, the European Society of Human Reproduction and Embryology, the American Heart Association, the Society for Endocrinology, and the European Society of Cardiology. The guideline has been formally endorsed by the European Society of Endocrinology, the Pediatric Endocrine Society, the European Society for Paediatric Endocrinology, the European Society of Human Reproduction and Embryology and the Endocrine Society. Advocacy groups appointed representatives who participated in pre-meeting discussions and in the consensus meeting