ESPE Abstracts

Introduction: Familial glucocorticoid deficiency (FGD), also known as hereditary resistance to ACTH, is a rare autosomal recessive disease characterized by an isolated deficiency of glucocorticoids. We report the case of a child who presented with type 1 FGD due to mutation of the ACTH receptor, melanocortin-2 receptor (MC2R), associated with monosomy 9p.

Case presentation: A 1-day-old female patient was born to consanguineous parents (second degree). Her birth weight and length were 2.7 kg and 49 cm, respectively. She was admitted to the neonatal unit for suspicion of metabolic disease because there was a family history of 2 previous deaths. One sister and one brother died 3 and 04 days respectively after birth due to dyspnea and hypoglycemia. Another 4-years-old brother was healthy. On examination, hyperpigmentation of the skin was noted with mild facial dysmorphism, she had a normal genitalia. Endocrine investigations revealed hypoglycemia, low cortisol levels (7,55 nmol/L, normal range: 138 - 500) with extremely elevated ACTH levels (1537 pg/mL, normal range: 6.4–40). Oral hydrocortisone treatment dose of 20 mg/m² per day was started. Caryotyping revealed a partial monosomy 9 and molecular analysis of the patient revealed a novel homozygous mutation c.112G˃Ap.(Gly38Arg) in MC2R which is compatible with the clinical diagnosis of familial glucocorticoid deficiency type1.

Discussion: The common presentation of FGD occurs during the neonatal period, typically with hypoglycemia and hyperpigmentation, as shown in our patient. Sequence analysis revealed a homozygous deletion of 1 nucleotide at position c.112 of the MC2R gene. This mutation has not been described in the literature so far. Screening of family members for gene mutation revealed both parents are heterozygous. The dilemma in our case was that our patient also had a deletion 9p syndrome. Mutation of the court arm of chromosome 9 has been associated with other disorders, with or without additional features of monosomy 9, but never with adrenal deficiency, especially with a MC2R mutation.

Conclusion: This rare disease (MC2R mutation) needs to be considered when dealing with any case of hypoglycemia and hyperpigmentation. However, further research is required to understand the mechanism that explains the association between deletion 9p syndrome and the MC2R mutation.