Familial Glucocorticoid Deficiency Type 4 due to NNT Gene Mutation: A Case Report
S Priyadarshini, S Bhavani, K. Umamageswari, Peter Prasanth KumarAbstract
Background:
Familial glucocorticoid deficiency (FGD) is a spectrum of autosomal recessive disorder, characterized by adrenal unresponsiveness to adrenocorticotropic hormone (ACTH). It is an uncommon cause of primary adrenal insufficiency.
Clinical Description:
A 16 month-old female child, born of consanguineous marriage, presented with an acute onset of respiratory distress with fever, associated with reduced activity and poor growth over past several months. Mother noticed diffuse hyperpigmentation, which had been progressing since the age of 6 months. There were two sibling deaths earlier. On examination, child was underweight and wasted with stable blood pressure and perfusion.
Management and Outcome:
Evaluation revealed anemia, with normal kidney and liver function tests, serum electrolytes, and blood gas analysis. The patient was negative for tuberculosis and retroviral infection. Endocrine testing revealed significantly low cortisol, normal aldosterone, and markedly elevated ACTH levels, suggestive of primary glucocorticoid deficiency. Genetic analysis identified a homozygous missense variant of unknown significance (VUS) in exon 5 of nicotinamide nucleotide transhydrogenase (
Conclusion:
This case is presented for its rarity and the importance of early diagnosis and prompt treatment, thereby avoiding life-threatening adrenal crisis. This case also highlights the need for keeping a high index of suspicion for considering FGD in families with hyperpigmentation associated with childhood mortality.