Congenital aldosterone deficiency and its resistance

Aldosterone synthase deficiency (ASD), which is caused by a genetic defect in CYP11B2, involves a deficiency in aldosterone alone. Newborn and early childhood ASD patients can present with salt-wasting symptoms. In severe cases, this can lead to shock and be life-threatening. ASD must also be differentiated from another disease, pseudohypoaldosteronism type 1 (PHA1), which involves resistance to aldosterone. PHA1 can be classified into PHA1a, PHA1b, and secondary PHA1. PHA1a is caused by a heterozygous defect in NR3C2, which encodes the mineralocorticoid receptor. PHA1b is an autosomal recessive disorder caused by defects in the 3 epithelial sodium channel subunits α, β, and γ, encoded by SCNN1A, SCNN1B, and SCNN1G. Since ASD is a very rare disorder, the "The Intractable Adrenal Disorders Research by the Ministry of Health, Labour, and Welfare" developed the "Diagnostic criteria and severity classification for aldosterone synthase deficiency" to better understand the disorder. The criteria are as follows: Clinical symptoms: patient meets criteria 1 and 2. 1) Presents with salt-wasting symptoms (poor feeding, vomiting, dehydration, poor weight gain). 2) No skin pigmentation. Laboratory findings: patient meets criteria 1 through 3. 1) Low serum sodium and high serum potassium. 2) Low to normal plasma aldosterone and high plasma renin activity or high plasma active renin concentration. 3) No low blood cortisol level. Diagnoses of exclusion include PHA1, 21-hydroxylase deficiency, congenital lipoid adrenal hyperplasia, and congenital adrenal hypoplasia. We believe that the diagnostic criteria of ASD will enable clinicians and researchers to better understand congenital aldosterone deficiency.