Antenatal diagnosis and early postnatal management of a neonate with type 1 familial glucocorticoid deficiency

Familial glucocorticoid deficiency (FGD) is a rare inherited cause of primary adrenal insufficiency, characterised by cortisol deficiency, without mineralocorticoid involvement. Affected patients commonly present in infancy or early childhood with hypoglycaemia, seizures, generalised hyperpigmentation and failure to thrive. Late diagnosis may lead to adverse neurological outcomes, usually resulting from repeated hypoglycaemic episodes. A family history of sibling deaths or affected relatives is often observed. Mutations in the gene encoding adrenocorticotropin receptor (melanocortin 2 receptor, <i>MC2R</i>), comprise about 25% of FGD cases (type 1 FGD). Here, we describe an infant born to parents with third-degree consanguinity and a history of unexplained neonatal deaths in two previous siblings, who had hyperpigmentation and hypoglycaemia. Genetic testing revealed both parents to be heterozygous for the <i>MC2R</i> gene variant c.701C>C/T (p.Pro234Leu). In the current pregnancy, amniocentesis performed for prenatal diagnosis confirmed the fetus to be homozygous for the same mutation as the parents, indicating the fetus would be affected with type I FGD. After birth, the infant was managed in the neonatal intensive care unit, and despite markedly low cortisol levels, prompt initiation of glucocorticoid replacement therapy resulted in the prevention of hypoglycaemia and adrenal crisis, with a favourable outcome. Our case is unique due to the antenatal diagnosis of FGD, allowing for proactive postnatal management and prevention of complications.