Le insidie della iperplasia surrenalica congenita tra eterogeneità genetica e variabilità fenotipica

Abstract

Congenital adrenal hyperplasia (CAH) is a heterogeneous group of autosomal recessive disorders affecting adrenal steroidogenesis. The most common form is 21-hydroxylase deficiency (CYP21A2), while mutations in other genes, such as STAR, may cause rare and severe forms with subtle onset. The paper describes two clinical cases: a male newborn who, at two weeks of life, developed a salt-wasting adrenal crisis with mild signs of hyperandrogenism (penile hypertrophy and scrotal hyperpigmentation), and a female infant with congenital lipoid adrenal hyperplasia (CLAH) due to a STAR mutation, who presented with progressive lethargy, poor feeding and diffuse hyperpigmentation preceding a severe hyponatremic adrenal crisis at six months of age. In both patients diagnosis was based on hormonal findings (elevated ACTH, low or absent cortisol) and confirmed by genetic testing, while treatment included steroid replacement therapy, correction of electrolyte imbalance and specialist follow-up. These cases underline the need for careful clinical and biochemical assessment, even in the absence of genital anomalies, and highlight the importance of molecular studies to define the genetic profile and plan personalised therapy.