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MCID: FML063
MIFTS: 58
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Familial Glucocorticoid Deficiency
Categories:
Endocrine diseases, Genetic diseases, Neuronal diseases, Rare diseases, Skin diseases
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MalaCards integrated aliases for Familial Glucocorticoid Deficiency:
Characteristics:Orphanet epidemiological data:58
familial glucocorticoid deficiency
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Childhood; Classifications:
MalaCards categories:
Global: Rare diseases Genetic diseases Anatomical: Endocrine diseases Neuronal diseases Skin diseases
ICD10:
33
Orphanet: 58
Rare endocrine diseases |
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GARD :
20
The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 361 Definition Familial glucocorticoid deficiency (FGD) is a group of primary adrenal insufficiencies characterized clinically by neonatal hyperpigmentation, hypoglycemia, failure to thrive, and recurrent infections, and biochemically by glucocorticoid deficiency without mineralocorticoid deficiency. Epidemiology The prevalence is unknown. In Ireland there is a prevalence of around 1/200,000, but this is likely to be skewed by a high prevalence in the Irish Traveler sub-population. Clinical description FGD usually presents in infancy or early childhood with hyperpigmentation of the skin and gums (present at birth or that develops over time), hypoglycemic seizures and failure to thrive. Recurrent infections are also a common finding (and may be the presenting sign in older children). Weakness, fatigue, weight loss, anorexia, vomiting, flank or abdominal pain, constipation and diarrhea are additional symptoms seen in some patients due to hypocortisolemia. Hypoglycemic crises resulting in convulsions can lead to coma or death if untreated and recurrent hypolglycemia may lead to neurological sequelae (i.e. learning disabilities, intellectual deficit, and sometimes severe, neuronal damage leading to major sensory and motor defects such as quadriplegia). Tall stature has been reported in some patients with FGD, typically those with MC2R gene defects. MRAP defects have been associated with a more severe disease and an earlier age of onset while a milder phenotype is seen in those with defects in the MCM4 gene (Irish Traveler FGD). Etiology FGD is due, in most cases, to defects in the adrenocorticotropin (ACTH) receptor, or its signaling pathway, resulting in a failure of the cells of zona fasciculata in the adrenal cortex to respond appropriately to adrenocorticotrophic hormone (ACTH), leading to a glucocorticoid deficiency. These defects are most commonly caused by mutations in MC2R (18p11.2), accounting for 25% of cases, and MRAP (21q22.1), accounting for 20% of cases. Other mutations reported in patients with FGD include MCM4 (8q12-q13), probably uniquely in the Irish Traveler population; NNT (5p12), accounting for around 15% of cases; and TXNRD2 (22q11.21). Certain partially inactivating mutations of STAR (8p11.2) or CYP11A1 (15q23-q24) can cause a phenotype that masquerades as FGD. Diagnostic methods Diagnosis is based on clinical and laboratory findings. Patients have high plasma ACTH and low serum morning cortisol levels that do not respond to exogenous ACTH stimulation. Mineralocorticoid function is normal. Molecular genetic testing revealing a mutation in one of the disease causing genes confirms diagnosis of FGD. Differential diagnosis The main differential diagnosis of FGD is Addison's disease (usually of autoimmune origin), in which case a mineralocorticoid deficiency is present. Other differential diagnoses include triple A syndrome, congenital adrenal hyperplasia and other acquired causes of primary adrenal insufficiency (see these terms). Antenatal diagnosis Prenatal diagnosis is possible in families with a known disease causing mutation but is rarely performed. Genetic counseling FDG is inherited in an autosomal recessive manner. Genetic counseling is possible. Management and treatment Treatment consists of a replacement therapy with oral hydrocortisone. A dosage of 10-12 mg/m2/day (usually divided into three doses) normalizes cortisol and reduces, but rarely normalizes, ACTH. Dose modification is necessary during stresses such as surgery or intercurrent illness, and patients should have injectable hydrocortisone available for emergencies and carry a medical alert type bracelet or card. Prompt and adequate treatment of a hypoglycemic crisis is essential. Treatment is life-long. Prognosis The prognosis is good for patients who are diagnosed and treated early. Only when left untreated is FGD a disease with high morbidity (neurological sequelae) and mortality.
MalaCards based summary : Familial Glucocorticoid Deficiency, also known as glucocorticoid deficiency, is related to glucocorticoid deficiency 1 and glucocorticoid deficiency 2. An important gene associated with Familial Glucocorticoid Deficiency is MC2R (Melanocortin 2 Receptor), and among its related pathways/superpathways are Aldosterone synthesis and secretion and Corticotropin-releasing hormone signaling pathway. The drugs Dexamethasone acetate and Dexamethasone have been mentioned in the context of this disorder. Affiliated tissues include adrenal gland, cortex and adrenal cortex, and related phenotypes are decreased circulating cortisol level and failure to thrive Disease Ontology : 12 An adrenal cortex disease that is characterized by insufficent production of glucocorticoids. MedlinePlus Genetics : 43 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 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 sugar (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. KEGG : 36 Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease characterized by glucocorticoid deficiency despite high levels of plasma ACTH. Affected individuals typically present within the first few months of life with symptoms related to cortisol deficiency, including recurrent illnesses or infections, hypoglycemia, convulsions, failure to thrive and shock. The disease is life threatening if untreated. Glucocorticoid replacement is the recommended treatment. It has been reported that FGD is caused by mutation of the ACTH receptor (MC2R) and the accessory protein (MRAP). Wikipedia : 73 Glucocorticoid deficiency 1 is an adrenocortical failure characterized by low levels of plasma cortisol... more... |
Human phenotypes related to Familial Glucocorticoid Deficiency:58 31 (show all 36)
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Drugs for Familial Glucocorticoid Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):(show all 21)
Interventional clinical trials:
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MalaCards organs/tissues related to Familial Glucocorticoid Deficiency:40
Adrenal Gland,
Cortex,
Adrenal Cortex,
Pituitary,
Thyroid,
Hypothalamus,
Thymus
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Articles related to Familial Glucocorticoid Deficiency:(show top 50) (show all 476)
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Genes related to Familial Glucocorticoid Deficiency (7 elite genes):(show all 38) - Elite gene
- Cancer Census gene in COSMIC
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ClinVar genetic disease variations for Familial Glucocorticoid Deficiency:6 (show top 50) (show all 206)
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Search
GEO
for disease gene expression data for Familial Glucocorticoid Deficiency.
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Pathways related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:
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Biological processes related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:(show all 17)
Molecular functions related to Familial Glucocorticoid Deficiency according to GeneCards Suite gene sharing:
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