ESPE Abstracts (2018) 89 P-P3-021

ESPE2018 Poster Presentations Adrenals and HPA Axis P3 (32 abstracts)

Presenting Features, Clinical Characteristics and Follow up of Familial Isolated Glucocorticoid Deficiency (FGD) due to Mutations in MC2R and MRAP Genes

Mehmet Nuri Ozbek a , Nezehat Doğan Karaşin a , Huseyin Demirbilek b , Meliha Demiral a , Rıza Taner Baran c & Tülay Güran d

aClinics of Paediatric Endocrinology, Diyarbakir Children State Hospital, Diyarbakır, Turkey; bDepartment of Pahediatric Endocrinology, Hacettepe University Faculty of Medicine, Ankara, Turkey; cClinics of Paediatric Endocrinology, Antalya Training and Research Hospital, Antalya, Turkey; dDepartment of Paediatric Endocrinology, Marmara University School of Medicine, İstanbul, Turkey

Objectives: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized with isolated glucocorticoid deficiency. Melanocortin receptor 2 (MC2R) mediates the functions of adrenocorticotropic hormone (ACTH) in the adrenal cortex. MC2R accessory protein (MRAP), a transmembrane protein, involves in the trafficking of MC2R to the cell surface. Mutations in MC2R and MRAP genes cause FGD type 1 and 2. Herein, we evaluate the clinical characteristics and follow-up of 6 cases with FGD due to mutations in MC2R and MRAP.

Patients and method: Data of 6 cases with FGD (5 with MC2R and one with MRAP mutations) followed at our pediatric endocrine center was collected from hospital files. Diagnosis of FGD was considered in case of elevated ACTH, inappropriately low cortisol and exclusion of other etiologies. Hydrocortisone was commenced as standard therapy. The results of molecular genetic analysis of the cases were already reported elsewhere*.

Results: Case characteristics, mutations and follow-up features are summarized in Table 1. During 26 to 115 months follow-up, case 2, 4 and 6 had neurodevelopmental delay (NDD), while the other 3 patients had completely normal neurodevelopment.

Conclusion: In this series evaluating a small number of FGD cases due to MC2R and MRAP mutations, early diagnosis and adherence to the hydrocortisone therapy found related to normal neurodevelopment, while, delay in diagnosis and poor compliance was associated with severe hypoglycemic convulsions and subsequent NDD.

*Guran T, et al., JCEM 2015.

Table 1
At presentationAt latest follow-up visit
Age (month)/sexComplaintsMutationCortisol (mcg/dL)ACTH (pg/mL)Weight (SDS)Height (SDS)Age (month)ACTH (pg/mL)Weight (SDS)Height (SDS)Additional findings
Case14/FHyperpigmentation HypoglycemiaConvulsionMC2R(560delT)0.04>15004.9 (−0.51)6 (−2)6113217.8 (−0.31)103 (−1.33)
Case212/FHyperpigmentation HypoglycemiaConvulsion IUGRMC2R(560delT)0.6200012.7 (2.58)92.2 (5.98)46200016 (0.11)108 (1.53)NDD Spasticity
Case39/MHyperpigmentation HypoglycemiaConvulsionMC2R(A233P)0.3200010.7 (1.45)76.5 (1.78)666.4820.8 (0.41)109.3 (−0.88)
Case418/FHyperpigmentation HypoglycemiaHypothyroidismMC2R(G226R)1.0>125018.3 (4.67)96.6 (4.63)10619.367 (4.07)138.2 (1.19)Primary hypo-thyroidism Obesity NDD
Case55days/FHyperpigmentation Hypoglycemia Convulsion Respiratory distressMC2R(560delT)0.268262.3 (−2.61)48 (−0.93)264.499.5 (−2.09)78.5 (−2.75)
Case634/FHyperpigmentation Hypoglycemia Convulsion HyperbilirubinemiMRAP(IVS3ds+1delG)<1.0>125019.7 (2.99)102.2 (2.03)11538.461.3 (3.18)136.5 (0.15)NDD Obesity Epilepsy

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