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Glucocorticoid deficiency 1(GCCD1)

MedGen UID:
885551
Concept ID:
C4049650
Disease or Syndrome
Synonyms: ACTH resistance; Adrenal unresponsiveness to acth; FAMILIAL GLUCOCORTICOID DEFICIENCY 1; GCCD1; Glucocorticoid deficiency, due to ACTH unresponsiveness
 
Gene (location): MC2R (18p11.21)
 
Monarch Initiative: MONDO:0024536
OMIM®: 202200

Definition

Familial glucocorticoid deficiency is an autosomal recessive disorder resulting from defects in the action of adrenocorticotropic hormone (ACTH) to stimulate glucocorticoid synthesis in the adrenal. Production of mineralocorticoids by the adrenal is normal. Patients present in early life with low or undetectable cortisol and, because of the failure of the negative feedback loop to the pituitary and hypothalamus, grossly elevated ACTH levels (summary by Clark et al., 2009). Genetic Heterogeneity of Familial Glucocorticoid Deficiency Familial glucocorticoid deficiency-2 (GCCD2; 607398) is caused by mutation in the MRAP gene (609196) on chromosome 21q22. GCCD3 (609197) has been mapped to chromosome 8q11.2-q13.2. GCCD4 with or without mineralocorticoid deficiency (614736) is caused by mutation in the NNT gene (607878) on chromosome 5p12. GCCD5 (617825) is caused by mutation in the TXNRD2 gene (606448) on chromosome 22q11. [from OMIM]

Additional description

From MedlinePlus Genetics
Familial glucocorticoid deficiency is a condition that occurs when the adrenal glands, which are hormone-producing glands located on top of each kidney, do not produce certain hormones called glucocorticoids. These hormones, which include cortisol and corticosterone, aid in immune system function, play a role in maintaining normal blood sugar (glucose) levels, help trigger nerve cell signaling in the brain, and serve many other purposes in the body.

A shortage of adrenal hormones (adrenal insufficiency) causes the signs and symptoms of familial glucocorticoid deficiency. These signs and symptoms often begin in infancy or early childhood. Most affected children first develop low blood glucose (hypoglycemia). These hypoglycemic children can fail to grow and gain weight at the expected rate (failure to thrive). If left untreated, hypoglycemia can lead to seizures, learning difficulties, and other neurological problems. Hypoglycemia that is left untreated for prolonged periods can lead to neurological damage and death. Other features of familial glucocorticoid deficiency can include recurrent infections and skin coloring darker than that of other family members (hyperpigmentation).

There are multiple types of familial glucocorticoid deficiency, which are distinguished by their genetic cause.  https://medlineplus.gov/genetics/condition/familial-glucocorticoid-deficiency

Clinical features

From HPO
Tall stature
MedGen UID:
69137
Concept ID:
C0241240
Finding
A height above that which is expected according to age and gender norms.
Failure to thrive
MedGen UID:
746019
Concept ID:
C2315100
Disease or Syndrome
Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Accelerated skeletal maturation
MedGen UID:
154262
Concept ID:
C0545053
Finding
An abnormally increased rate of skeletal maturation. Accelerated skeletal maturation can be diagnosed on the basis of an estimation of the bone age from radiographs of specific bones in the human body.
Recurrent infections
MedGen UID:
65998
Concept ID:
C0239998
Finding
Increased susceptibility to infections.
Recurrent hypoglycemia
MedGen UID:
335382
Concept ID:
C1846288
Finding
Recurrent episodes of decreased concentration of glucose in the blood.
Hyperpigmentation of the skin
MedGen UID:
57992
Concept ID:
C0162834
Pathologic Function
A darkening of the skin related to an increase in melanin production and deposition.
Generalized hyperpigmentation
MedGen UID:
870432
Concept ID:
C4024878
Finding
Abnormal circulating aldosterone
MedGen UID:
808216
Concept ID:
C0857898
Finding
Decreased circulating cortisol level
MedGen UID:
322961
Concept ID:
C1836623
Finding
Abnormally reduced concentration of cortisol in the blood.
Abnormal circulating renin
MedGen UID:
866691
Concept ID:
C4021038
Finding
A deviation from the normal concentration of renin in the blood, a central hormone in the control of blood pressure and various other physiological functions.
Increased circulating ACTH level
MedGen UID:
867375
Concept ID:
C4021740
Finding
An abnormal increased in the concentration of corticotropin, also known as adrenocorticotropic hormone (ACTH), in the blood.
Abnormal response to ACTH stimulation test
MedGen UID:
1392823
Concept ID:
C4476953
Finding
An anomalous response to stimulation by administration of the adrenocorticotropic hormone (ACTH). ACTH stimulation normally stimulates the adrenal glands to release cortisol and adrenaline.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVGlucocorticoid deficiency 1

Recent clinical studies

Diagnosis

Tunkara H, Topor LS
J Pediatr 2022 May;244:e5. doi: 10.1016/j.jpeds.2022.01.022. PMID: 35534171
Özbek MN, Demiral M, Unal E, Karaşin ND, Baran RT, Demirbilek H
J Pediatr Endocrinol Metab 2021 Nov 25;34(11):1463-1468. Epub 2021 Jul 19 doi: 10.1515/jpem-2021-0150. PMID: 34271604
Maharaj A, Maudhoo A, Chan LF, Novoselova T, Prasad R, Metherell LA, Guasti L
J Steroid Biochem Mol Biol 2019 May;189:73-80. Epub 2019 Feb 25 doi: 10.1016/j.jsbmb.2019.02.012. PMID: 30817990
Habeb AM, Hughes CR, Al-Arabi R, Al-Muhamadi A, Clark AJ, Metherell LA
Eur J Pediatr 2013 Oct;172(10):1407-10. Epub 2013 May 26 doi: 10.1007/s00431-013-2044-1. PMID: 23708259
Meimaridou E, Hughes CR, Kowalczyk J, Chan LF, Clark AJ, Metherell LA
Endocr Dev 2013;24:57-66. Epub 2013 Feb 1 doi: 10.1159/000342504. PMID: 23392095

Therapy

Tunkara H, Topor LS
J Pediatr 2022 May;244:e5. doi: 10.1016/j.jpeds.2022.01.022. PMID: 35534171

Prognosis

Habeb AM, Hughes CR, Al-Arabi R, Al-Muhamadi A, Clark AJ, Metherell LA
Eur J Pediatr 2013 Oct;172(10):1407-10. Epub 2013 May 26 doi: 10.1007/s00431-013-2044-1. PMID: 23708259

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