![]() ![]() Echocardiography revealed no structural or functional heart abnormalities. Bone mineral density was in the range for osteopenia in both grown-up siblings. The adolescent patients had slow pubertal progression with low–normal testicular volume, while testicular endocrine function was normal. The urinary steroid metabolome showed normal excretion of cortisol metabolites. The three patients, who were homozygous for c.1575dup in the NNT gene, developed isolated glucocorticoid deficiency. The urinary steroid metabolome was determined by gas chromatography–mass spectrometry in the asymptomatic patient. Whole exome sequencing with a targeted interpretation of variants in genes related to PAI was performed in all the patients. ![]() PAI was diagnosed in the eldest two brothers after an Addisonian crisis and the third was diagnosed at the age of 4.5 months in the asymptomatic stage due to the genetic screening of family members. ![]() The patients were followed until the ages of 21.6, 20.2, and 4.2 years. We present the clinical and genetic characteristics of three family members with a biallelic novel pathogenic variant in the NNT gene. A limited number of these patients were previously described. Nicotinamide nucleotide transhydrogenase (NNT) deficiency causes primary adrenal insufficiency (PAI) and possibly some extra-adrenal manifestations. ![]()
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