Cortisone Reductase Deficiency 2 (CORTRD2)

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OMIM®: ⁵⁷ Cortisone reductase deficiency is a disorder in which there is a failure to regenerate the active glucocorticoid cortisol from cortisone via the enzyme 11-beta-hydroxysteroid dehydrogenase, encoded by the HSD11B1 gene. Purified 11-beta-HSD acts readily as a dehydrogenase, inactivating cortisol to cortisone; however, in the presence of a high NADPH/NADP+ ratio, generated in vivo through the activity of microsomal hexose-6-phosphate dehydrogenase (H6PD; 138090), 11-beta-HSD switches to ketoreductase activity and generates active glucocorticoid. Lack of cortisol regeneration stimulates ACTH-mediated adrenal hyperandrogenism, with males manifesting in early life with precocious pseudopuberty and females presenting later with hirsutism, oligomenorrhea, and infertility. Biochemically, CORTRD is diagnosed through the assessment of urinary cortisol and cortisone metabolites and consists of measuring the ratio of tetrahydrocortisol (THF) plus 5-alpha-THF to tetrahydrocortisone (THE), which in CORTRD patients is typically less than 0.1 (reference range, 0.7 to 1.2) (summary by Lawson et al., 2011). For a discussion of genetic heterogeneity of cortisone reductase deficiency, see CORTRD1 (604931). (614662) (Updated 08-Dec-2022)

MalaCards based summary: Cortisone Reductase Deficiency 2, also known as cortrd2, is related to intracranial hypertension, idiopathic and intracranial hypertension. An important gene associated with Cortisone Reductase Deficiency 2 is HSD11B1 (Hydroxysteroid 11-Beta Dehydrogenase 1), and among its related pathways/superpathways are Interleukin-4 and Interleukin-13 signaling and Metabolism of steroid hormones. Affiliated tissues include pituitary, liver and bone, and related phenotypes are obesity and acanthosis nigricans

UniProtKB/Swiss-Prot: ⁷³ An autosomal dominant error of cortisone metabolism characterized by a failure to regenerate cortisol from cortisone, resulting in increased cortisol clearance, activation of the hypothalamic- pituitary axis and ACTH-mediated adrenal androgen excess. Clinical features include hyperandrogenism resulting in hirsutism, oligo- amenorrhea, and infertility in females and premature pseudopuberty in males.

Disease Ontology: ¹¹ A cortisone reductase deficiency that is characterized by a failure to regenerate cortisol via the enzyme 11-beta-hydroxysteroid dehydrogenase, resulting in ACTH-mediated adrenal hyperandrogenism, and has material basis in autosomal dominant inheritance of heterozygous mutation in the 11-beta-hydroxysteroid dehydrogenase type I (HSD11B1) gene on chromosome 1q32.

Clinical features from OMIM®:

Search Clinical Trials, NIH Clinical Center for Cortisone Reductase Deficiency 2