Rare Forms of Congenital Adrenal Hyperplasia Affecting Electrolyte Homeostasis

Congenital adrenal hyperplasia (CAH) encompasses a group of monogenic and autosomal recessive diseases, with the most common form being 21-hydroxylase deficiency. However, rare forms of CAH, representing around 5% of cases, are attributed to five other enzymatic defects that disrupt steroidogenesis and impact electrolyte homeostasis. Enzymatic defects can occur at various stages of the steroidogenesis pathway, leading to impaired conversion of cholesterol into steroids. Defects in the steroidogenic acute regulatory protein, StAR, impede the free cholesterol from entering the mitochondria. If the cholesterol side-chain cleavage enzyme, P450scc, is not functional, cholesterol does not turn into pregnenolone, the first precursor of steroidogenesis. The 17-a-hydroxylase and 3B-hydroxysteroid dehydrogenase function are fundamental to reaching all the end hormones of adrenal steroidogenesis. Furthermore, the loss of function of 11-B-hydroxylase leads to no production of glucocorticoids and an excess of mineralocorticoids and androgens. The severity of these defects varies depending on the specific mutation carried by each individual, resulting in a wide range of manifestations that can present at different stages of life, necessitating lifelong management and care. This chapter reviews these rare CAH forms, focusing on their impact on electrolyte balance. It explores the epidemiology, genetic defects, pathophysiology, clinical presentation, diagnostic modalities, and approaches for these conditions.