# Unique Case Report: A Rare Association of 21-Hydroxylase Deficiency with Triple X Karyotype

## TL;DR

A 38-year-old woman was found to have a rare combination of 21-hydroxylase deficiency and Triple X syndrome, highlighting the need for detailed clinical evaluations.

## Contribution

This paper reports the first documented case of partial 21-hydroxylase deficiency co-occurring with a Triple X karyotype.

## Key findings

- The patient exhibited premature ovarian failure and hyperandrogenism linked to partial 21-hydroxylase deficiency.
- Genetic testing confirmed the presence of a Triple X karyotype, a rare condition not previously associated with 21-hydroxylase deficiency.
- The case emphasizes the importance of comprehensive evaluations for rare genetic co-occurrences.

## Abstract

Background: Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders characterized by impaired cortisol synthesis in the adrenal glands. Over 90% of CAH cases result from a deficiency of the enzyme 21-hydroxylase (21OHD). The clinical spectrum of 21OHD ranges from the severe, life-threatening salt-wasting classic form, often presenting with prenatal virilization in females, to the non-classic (milder) form, which lacks glucocorticoid deficiency. Females with the non-classic form may experience symptoms of hyperandrogenism or infertility later in life, while males with non-classic CAH are often undiagnosed due to the subtler presentation. The coexistence of genetic anomalies and CAH is rarely reported in the literature, particularly in cases involving Triple X syndrome—a condition typically associated with a mild and frequently underdiagnosed clinical course. Case presentation: Here, we present a unique case of a 38-year-old woman with a history of premature ovarian failure and subsequent clinical features of hyperandrogenism. Further investigation revealed a novel association between partial 21OHD and a Triple X karyotype—an association not previously documented in the literature. Conclusions: This case highlights the potential for coexisting rare genetic conditions and underscores the critical importance of thorough and meticulous clinical evaluation.