Abstract
Objectives
Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterised by isolated glucocorticoid deficiency. Melanocortin receptor 2 (MC2R) mediates the functions of adrenocorticotropic hormone (ACTH) in the adrenal cortex. MC2R accessory protein (MRAP) is a transmembrane protein involved in the trafficking of MC2R to the cell surface. Mutations in MC2R and MRAP genes cause FGD type 1 and 2. In the present case series, we evaluate the clinical characteristics and long-term follow-up of six cases with FGD due to mutations in MC2R and MRAP.
Case presentation
Data of six cases with FGD (five with mutations in MC2R and one with a mutation in MRAP) who were being followed at our paediatric endocrine centre was evaluated. Diagnosis of FGD was considered in case of elevated ACTH and inappropriately low cortisol level, and exclusion of other aetiologies. The main presenting complaints were hyperpigmentation and hypoglycaemic convulsion in all cases. During a follow-up period of 26–115 months, one patient with homozygous 560delT mutation in MC2R, one female with G226R mutation in MC2R and one female with IVS3ds+1delG mutation in MRAP had a neurodevelopmental delay (NDD), while the other three patients had normal neurodevelopment.
Conclusions
FGD patients due to MC2R and MRAP mutations with early diagnosis and compliance to the hydrocortisone therapy had normal neurodevelopment, while delay in diagnosis and poor compliance was associated with severe hypoglycaemic convulsions and subsequent complications NDD.
Acknowledgments
There is no acknowledgment.
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Research funding: There is no research funding.
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Author contributions: Surgical and Medical Practices: Hüseyin Demirbilek, Mehmet Nuri Özbek, Meliha Demiral; Concept: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek, Edip Unal, Nezahat Doğan Karaşin; Design: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek, Edip Unal, Rıza Taner Baran; Data Collection or Processing: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek, Edip Unal, Nezahat Doğan Karaşin, Rıza Taner Baran; Analysis or Interpretation: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek; Literature Search: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek; Writing: Mehmet Nuri Özbek, Meliha Demiral, Hüseyin Demirbilek. All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: There is no conflict of interest.
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Informed consent: Informed consent was obtained from all individuals included in this study.
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Ethical approval: The local Institutional Review Board deemed the study exempt from review.
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