Congenital Adrenal Hyperplasia in the Mediterranean: A Concise Overview

Background: Congenital Adrenal Hyperplasia (CAH) is a group of autosomal recessive disorders caused by impaired adrenal steroidogenesis, most frequently due to pathogenic variants in the CYP21A2 gene leading to 21-hydroxylase deficiency (21-OHD). Epidemiology and management vary across the Mediterranean Basin as a result of genetic and healthcare differences. Objective: To provide an overview of the epidemiology, diagnostic approaches and treatment patterns of CAH in Mediterranean countries. Methods: A structured review of the literature was performed using PubMed, using combined disease-related, geographic and methodological terms. Eligible studies reporting on epidemiology, diagnosis, or management of CAH were included. Data on study design, population characteristics, incidence, diagnostics, genetics and treatment availability were extracted. Results: Data were collected from 23 Mediterranean and neighboring regions covering over 8.7 million screened newborns. In countries with established newborn screening (e.g., Spain, Italy, France, Greece), the incidence of classic CAH ranged from 1:10,000 to 1:25,000 live births. Higher rates were reported in parts of North Africa and the Eastern Mediterranean. Diagnostic set-up and access to biochemical and genetic confirmation varied widely. Hydrocortisone remains the primary therapy, while access to mineralocorticoids and modified-release glucocorticoids differed across settings. Conclusions: Overall, considerable heterogeneity in CAH epidemiology and care exists across the Mediterranean region. Genetic factors such as founder effects, consanguinity and healthcare organization contribute to these differences. Expanding newborn screening, improving diagnostics and availability to treatments are critical to reducing disparities in CAH care.