ESPE Abstracts

Background: In humans, loss-of-function mutations in Nicotinamide nucleotide transhydrogenase (NNT) cause familial glucocorticoid deficiency, a potentially fatal, adrenal-specific disorder characterized by increased ACTH and reduced cortisol levels. NNT is a highly conserved inner mitochondrial membrane protein, which supplies high concentrations of NADPH for detoxification of reactive oxygen species (ROS) by glutathione and thioredoxin pathways.<p class="abstext"...

Background: SGPL1 deficiency is associated with a pathological accumulation of sphingolipid intermediates and a multi-systemic condition incorporating primary adrenal insufficiency. Sphingolipid intermediates such as ceramide, sphingosine and sphingosine 1-phosphate are postulated to act as modulators of the steroidogenic pathway, often acting as second messengers altering downstream expression of steroid responsive transcriptional elements. Ceramide and sphin...

Background: Primary adrenal insufficiency (PAI) is most commonly congenital in children. PAI is genetically heterogeneous with some gene defects causing syndromic disease. A third of patients have no genetic diagnosis meaning their prognosis is uncertain. We recently investigated families with a novel combination of PAI and steroid resistant nephrotic syndrome.Objective and hypotheses: To discover the genetic defect underlying this syndrome.<p class=...