Screening neonatale della Sindrome Adreno-genitale Congenita (SAG): stato dell’arte

Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder due to enzyme deficiencies in the adrenal steroidogenesis pathway, leading to impaired cortisol biosynthesis and intermediate precursors’ accumulation. More than 90% of cases are due to a 21-hydroxylase deficiency (21-OHD) with 17-hydroxyprogesterone (17-OHP) accumulation; phenotypic spectrum is very broad and depends mainly on the severity of the enzyme deficiency and the sex of the subject. If left unrecognised and untreated, severe forms can cause a life-threatening adrenal crisis with salt loss in the first weeks of life. For this reason, neonatal screening programmes based on 17-OHP determination have been introduced since 1977 and subsequently implemented. Despite its undisputed clinical usefulness, neonatal CAH screening still has many limitations, due to a high number of false positives. In the early 2000s, the introduction of tandem mass spectrometry (HPLC-MS/MS) made it possible to minimise intra- and inter-laboratory variability and inaccuracy in the quantification of steroid hormones. The introduction of this second-tier test has reduced the recall rate of newborns. By avoiding unnecessary sampling and visits, it has thus reduced healthcare costs and additional stress for families.