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SummaryAutoimmune polyendocrinopathy type 1 (APS1) is an autosomal recessive disorder characterized by autoimmune hypoparathyroidism, autoimmune adrenocortical failure, and mucocutaneous candidiasis. Recently, an autoimmune regulator gene (AIRE-1), which is located on chromosome 21q22.3, has been identified, and mutations in European kindreds with APS1 have been described. We used SSCP analysis and direct DNA sequencing to screen the entire 1,635-bp coding region of AIRE-1 in 12 British families with APS1. A 13-bp deletion (964del13) was found to account for 17 of the 24 possible mutant AIRE-1 alleles, in our kindreds. This mutation was found to occur de novo in one affected subject. A common haplotype spanning the AIRE-1 locus was found in chromosomes that carried the 964del13 mutation, suggesting a founder effect in our population. One of 576 normal subjects was also a heterozygous carrier of the 964del13 mutation. Six other point mutations were found in AIRE-1, including two 1-bp deletions, three missense mutations (R15L, L28P, and Y90C), and a nonsense mutation (R257*). The high frequency of the 964del13 allele and the clustering of the other AIRE-1 mutations may allow rapid molecular screening for APS1 in British kindreds. Furthermore, the prevalence of the 964del13 AIRE-1 mutation may have implications in the pathogenesis of the more common autoimmune endocrinopathies in our population.

At 1 month of age, dizygotic twins presented with failure to thrive, hyponatremic dehydration, and hyperkalemia. Renal function and glucocorticoid production were normal. Routine fluid and electrolyte replacement failed to correct the dehydration, and the administration of desoxycorticosterone gave no response. Urinary aldosterone levels were consistently elevated, and urinary excretion of sodium was disproportionately high. The patients responded to a daily supplementary intake of 3 g of sodium chloride, with correction of the hyponatremia and dehydration and return of serum potassium concentrations to normal. Salt supplementation was discontinued after 15 months. The twins continued to thrive on regular diet and maintained normal levels of serum sodium and potassium, yet their urinary and plasma aldosterone levels remained high. The observations suggest that the defect (1) may be familial and genetic, (2) may be caused by failure of the renal tubules to respond to aldosterone, and (3) is correctable by increased intake of sodium chloride.