An atypical case of familial glucocorticoid deficiency without pigmentation caused by coexistent homozygous mutations in MC2R (T152K) and MC1R (R160W).

The Journal of Clinical Endocrinology and Metabolism
Serap TuranLouise A Metherell

Abstract

Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disorder characterized by isolated cortisol deficiency. Mutations in the gene encoding the ACTH receptor (MC2R) account for 25% of cases. One significant feature is generalized skin hyperpigmentation, which is thought to be due to elevated ACTH acting on the melanocortin 1 receptor (MC1R). The aim of the study was to determine the cause of a nonhyperpigmented case of FGD. The patient presented at 4 yr of age with hypoglycemia after prolonged fasting during a respiratory tract infection. She had further hypoglycemic attacks and was diagnosed with isolated glucocorticoid deficiency at 6 yr of age. Her parents were consanguineous, and she had two unaffected sisters. Her physical examination was normal, except that her height and weight were greater than the 97th centile for a sex- and age-matched reference population. Interestingly, she had no hyperpigmentation despite very high ACTH levels. Nucleotide sequence analysis revealed homozygous mutations c.478C>T in MC1R and c.455C>A in MC2R leading to R160W and T152K changes in the amino acid sequences, respectively. The R160W MC1R change has previously been implicated in a red hair/pale skin phenotype, and MC2R -T...Continue Reading

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Citations

Feb 19, 2013·The Journal of Endocrinology·T V NovoselovaL F Chan
Mar 24, 2016·Cancer Letters·Ying LiuTian-Rui Xu
May 9, 2014·Pigment Cell & Melanoma Research·Jose C García-BorrónCelia Jiménez-Cervantes
Jan 3, 2013·Molecular and Cellular Endocrinology·Eirini MeimaridouLouise A Metherell
Aug 30, 2018·Physiological Reviews·Erika HarnoAnne White
Mar 25, 2019·Journal of the Endocrine Society·Yorihiro IwasakiNobuya Inagaki
Feb 22, 2017·Frontiers in Endocrinology·Davids FridmanisJanis Klovins

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Methods Mentioned

BETA
PCR
biopsy

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