A novel variant of familial glucocorticoid deficiency prevalent among the Irish Traveler population.

CONTEXT Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by distinct clinical, biochemical, and genetic abnormalities. The prevalence of FGD is unknown, with the likelihood that cases remain undiagnosed. We noted a significant proportion of our FGD cases are Irish Travelers. Irish Travelers are an endogamous nomadic group ethnically and genetically distinct from Roma gypsies. AIMS The objective of the study was to describe the clinical features and assess the prevalence of FGD amongst Irish Travelers in the Republic of Ireland and describe their phenotype. METHODS Diagnosis of FGD was based on clinical features, high ACTH, and low cortisol concentrations with normal renin and aldosterone concentrations and exclusion of other causes of adrenal failure. Data from the Republic of Ireland Census 2006 were used. RESULTS We identified 21 cases of FGD, generating an overall prevalence of one in 201,898. We report nine Irish Travelers (five females) with FGD related to a new gene negative for melanocortin-2 receptor and melanocortin-2 receptor accessory protein mutations. Of a total population of 22,557 Travelers, this yields a disease prevalence of one in 2506 with a carrier frequency of one in 25 in this group and represents a prevalence of one in 665 and a carrier frequency of one in 13 in the 4- to 15-yr Traveler age group. All nine children had a later onset of FGD due to the fact that their initial investigations revealed normal cortisol (422-575 nmol/liter) and ACTH (<34 ng/liter) concentrations. CONCLUSION We report a high prevalence of FGD among Irish Travelers. Their subtle phenotype and initial normal biochemistry may delay the early diagnosis of FGD.