SGPL1 and Primary hypothyroidism: However, the most recent discovered disorder in this category is sphingosine-1-phosphate lyase 1 (SGPL1) deficiency, in which recessive loss-of-function SGPL1 mutations cause syndromic adrenal insufficiency associated with steroid-resistant nephrotic syndrome, variably accompanied by ichthyosis, primary hypothyroidism, cryptorchidism, immunodeficiency and neurological anomalies [147–149].