Identifying the First Val281L Mutation Causing Nonclassic Congenital Adrenal Hyperplasia in the Central-East Region of Tunisia

TL;DR

This paper reports a case of nonclassic congenital adrenal hyperplasia in Tunisia, highlighting the importance of genetic testing for diagnosis and family screening.

Contribution

The study identifies the Val281Leu mutation in the CYP21A2 gene in a Tunisian patient, marking its first report in the Central-East region.

Findings

A 26-year-old female with NCAH was found to have the V281L mutation in the CYP21A2 gene.

Family testing revealed the patient's mother was homozygous and the father heterozygous for the mutation.

Genetic testing confirmed the diagnosis and highlighted the role of carrier screening in managing NCAH.

Abstract

Nonclassic congenital adrenal hyperplasia (NCAH) is a genetic disorder characterized by mutations in the genes encoding enzymes involved in cortisol production, most commonly the 21-hydroxylase enzyme. Unlike classic congenital adrenal hyperplasia (CAH), NCAH typically presents later in life with milder symptoms. The diagnosis of NCAH can be challenging due to its nonspecific symptoms and variable presentation. Early detection is crucial for timely intervention and management, particularly in families with a history of the condition. We report a case of NCAH in a patient from the Central-East Region of Tunisia, in whom the subsequent genetic testing revealed a Val281Leu (V281L) mutation in the CYP21A2 gene.

A 26-year-old female presented with facial hirsutism and irregular menstrual cycles. Physical examination revealed mild hirsutism and laboratory tests showed elevated levels of testosterone and 17-hydroxyprogesterone (17-OHP). A provisional diagnosis of NCAH was made, subsequently confirmed by an adrenocorticotropic hormone (ACTH) stimulation test demonstrating an exaggerated 17-OHP response. Genetic testing revealed heterozygosity for the V281L mutation. Family testing showed the patient's mother to be homozygous and the father heterozygous for the mutation.

This report highlights the importance of recognizing subtle symptoms of NCAH for early diagnosis and management. Genetic testing aids in confirming the diagnosis and identifying carriers within families. Treatment with glucocorticoids aims to suppress adrenal androgen production and manage symptoms. Regular follow-up is essential to monitor treatment response and adjust medication as needed. NCAH can present with subtle symptoms, necessitating a high index of suspicion for a proper diagnosis. Genetic testing plays a crucial role in confirming the diagnosis and identifying carriers within families. Early intervention and regular follow-up improve outcomes in affected individuals. This report also underscores the significance of genetic testing in the management of NCAH and highlights the need for increased awareness about this condition among healthcare providers.

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