Familial Hypoadrenocorticism

Hereditary forms of Addison disease that may exhibit autosomal recessive or X-linked inheritance. They are characterized by severe neurological symptoms, APNEA; and death in infancy. OMIM: 240200

Also Known As:

Hypoadrenocorticism, Familial; AHC with Isolated Gonadotropin Deficiency; Addison Disease, X-Linked; Adrenal Hypoplasia, Congenital; Adrenal Hypoplasia, Congenital, with Hypogonadotropic Hypogonadism; Complex Glycerol Kinase Deficiency; Cytomegalic Adrenocortical Hypoplasia; Familial X-linked Addison Disease; X-linked Adrenal Hypoplasia; X-linked Congenital Adrenal Hypoplasia; Xp21 Contiguous Gene Deletion Syndrome; Addison Disease, X Linked; Adrenal Hypoplasia, X-linked; Congenital Adrenal Hypoplasia; Congenital Adrenal Hypoplasias; Cytomegalic Adrenocortical Hypoplasias; Familial Hypoadrenocorticisms; Familial X linked Addison Disease; Hypoadrenocorticisms, Familial; Hypoplasia, Congenital Adrenal; X linked Adrenal Hypoplasia; X linked Congenital Adrenal Hypoplasia; X-Linked Addison Disease

Networked: 154 relevant articles (1 outcomes, 4 trials/studies)

Relationship Network

Disease Context: Research Results

Endocrine System Diseases: 968
- Adrenal Gland Diseases: 24
  - Adrenal Insufficiency: 3937
    - Addison Disease: 1725
      - Familial Hypoadrenocorticism: 154

Related Diseases

1.	Dosage-sensitive sex reversal
2.	Intellectual Disability (Idiocy)
3.	Hypogonadism (Hypergonadotropic Hypogonadism)
4.	Duchenne Muscular Dystrophy (Muscular Dystrophy, Becker)
5.	Familial Hypoadrenocorticism

Experts

1.	Achermann, John C: 4 articles (01/2011 - 01/2002)
2.	Choi, Hueng-Sik: 4 articles (03/2010 - 05/2004)
3.	Beck-Peccoz, Paolo: 4 articles (05/2006 - 01/2002)
4.	Mantovani, Giovanna: 4 articles (05/2006 - 01/2002)
5.	Persani, Luca: 4 articles (05/2006 - 01/2002)
6.	Spada, Anna: 4 articles (05/2006 - 01/2002)
7.	Jameson, J L: 3 articles (03/2007 - 01/2001)
8.	Jameson, J Larry: 3 articles (01/2003 - 01/2002)
9.	Chen, Qiuli: 2 articles (07/2021 - 06/2019)
10.	Du, Minlian: 2 articles (07/2021 - 06/2019)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Familial Hypoadrenocorticism:

1.	Steroidogenic Factor 1IBA 06/26/2019 - "The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). " 12/01/2005 - "We analyzed mRNA by slot-blot hybridization and also quantified mRNA for transcription factors necessary for adrenocortical development by quantitative real-time PCR: steroidogenic factor 1 and dosage-sensitive sex reversal, adrenal hypoplasia congenital, critical region on the X chromosome (DAX-1). " 08/01/2004 - "Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. " 08/01/2004 - "We measured mRNA expression of Sertoli cell, Sry-like HMG box protein 9 (Sox9); three upstream transcription factors, liver receptor homolog-1 (Lrh-1), steroidogenic factor 1, and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1; and one downstream factor, Müllerian-inhibiting substance. " 01/01/2001 - "Here, we consider mutations in KAL in X-linked Kallmann syndrome; DAX1 in X-linked adrenal hypoplasia congenita; the related orphan nuclear receptor, steroidogenic factor-1; leptin and prohormone convertase-1, which may influence GnRH release and processing; the GnRH receptor; the pituitary transcription factors, HESX-1, LHX3 and PROP-1; and the gonadotropins, follicle stimulating hormone (FSH) and luteinizing hormone (LH). "
2.	EnzymesIBA 07/01/2003 - "Two had the glycerol kinase deficiency as part of an Xp21 contiguous gene deletion syndrome-complex form-and three had an isolated form of the enzyme deficiency. " 01/01/1994 - "Glycerol kinase deficiency occurs either as a relatively benign isolated enzyme deficiency, or as part of a syndrome resulting from a microdeletion in the p21 region of the X chromosome associated with congenital adrenal hypoplasia and/or Duchenne muscular dystrophy. " 10/01/1991 - "The subjects were divided into 3 groups: those with androgen excess (A+) comprised a group of 13 patients with classical 21-hydroxylase deficiency and one with 11-beta-hydroxylase deficiency; a normal or reduced androgen (a+) group was represented by one patient with late-onset 21-hydroxylase deficiency and one with congenital adrenal hypoplasia; and a group with absent androgen (A-) consisted of 5 patients with a cholesterol side-chain cleaving-enzyme deficiency. " 08/01/2004 - "Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. "
3.	Dihydrotachysterol (AT 10)IBA 08/01/2004 - "Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. "
4.	3 (or 17)-beta-hydroxysteroid dehydrogenaseIBA 08/01/2004 - "Placebo-treated ArKO ovaries have increased Sox9 (15-fold; P < 0.001), Müllerian-inhibiting substance (2.9-fold), Lrh-1 (7.7-fold), and dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on the X chromosome gene 1 (12-fold) expression compared with Wt at 10 wk. Steroidogenic factor 1 was similar to Wt. Consistent with increased serum T levels and Leydig cells in their ovaries, placebo-treated ArKO ovaries had increased 17alpha-hydroxylase, 17beta-hydroxysteroid dehydrogenase type-3, and 17beta-hydroxysteroid dehydrogenase type-1 expression compared with Wt at 10 wk. E2 treatment for 3 wk improved the ovarian phenotype, decreased development of Sertoli cells, decreased the expression of Sox9, Lrh-1, and the steroidogenic enzymes in ArKO ovaries, and induced ovulation in some cases. "
5.	HyperglycerolemiaIBA 11/01/1994 - "Molecular mapping revealed that the deletion extended from the 3' end of the DMD gene to a site telomeric to the loci for X-linked congenital adrenal hypoplasia and glycerol kinase deficiency. " 11/01/1989 - "The cause was a small X-chromosomal deletion within Xp21 resulting in the syndrome of congenital adrenal hypoplasia with glycerol kinase deficiency. " 11/01/1989 - "Congenital adrenal hypoplasia and glycerol kinase deficiency." 06/01/1989 - "We report a case of X-linked adrenal hypoplasia associated with glycerol kinase deficiency in a boy. " 06/01/1989 - "[Prenatal diagnosis of X-linked adrenal hypoplasia associated with glycerol kinase deficiency]."
6.	Cytoplasmic and Nuclear Receptors (Nuclear Receptors)IBA 11/01/2006 - "Mutations in the human nuclear receptor, DAX1, cause X-linked adrenal hypoplasia congenita (AHC). " 07/01/2000 - "X-linked adrenal hypoplasia congenita (AHC) is a rare developmental disorder of the human adrenal cortex that is caused by a mutation of the DAX-1 gene, a member of the nuclear hormone receptor superfamily. " 08/01/1998 - "X-linked congenital adrenal hypoplasia (AHC) is a rare developmental disorder of the human adrenal cortex and is caused by deletion or mutation of the DAX-1 gene, a recently discovered member of the nuclear hormone receptor superfamily. " 07/01/1996 - "The gene responsible for X-linked adrenal hypoplasia congenita, DAX1, encodes a member of the nuclear hormone receptor superfamily. " 04/01/1996 - "An unusual member of the nuclear hormone receptor superfamily, DAX1, maps to the DSS critical region and is responsible for X-linked adrenal hypoplasia congenita. "
7.	Proteins (Proteins, Gene)FDA Link 06/11/2002 - "X-linked adrenal hypoplasia congenita is caused by abnormal nuclear localization of the DAX-1 protein." 10/01/1996 - "Truncation at the C-terminus of the DAX-1 protein impairs its biological actions in patients with X-linked adrenal hypoplasia congenita." 05/01/2021 - "A novel stop-loss DAX1 variant affecting its protein-interaction with SF1 precedes the adrenal hypoplasia congenital with rare spontaneous precocious puberty and elevated hypothalamic-pituitary-gonadal/adrenal axis responses." 10/01/2022 - "Biallelic variants resulting in markedly reduced amounts of normal protein have been reported in two separate recessive pediatric syndromes: facial dysmorphism, immunodeficiency, livedo, and short stature as well as intrauterine growth restriction, metaphyseal dysplasia, adrenal hypoplasia congenital, and genital anomalies. " 04/01/2010 - "X-linked adrenal hypoplasia congenita (AHC) is a rare disorder caused by mutations or complete deletion of the NR0B1 gene that encodes the DAX-1 protein, an orphan member of the nuclear receptor superfamily. "
8.	DNA (Deoxyribonucleic Acid)IBA 07/17/1995 - "In this report, we describe rapid molecular cytogenetic identification of deleted DNA in affected males with the Xp21 contiguous gene syndrome (complex glycerol kinase deficiency, CGKD) and female carriers for this disorder. " 02/01/1996 - "We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism by using PCR amplification of genomic DNA and its complete exonic sequencing. " 01/01/1996 - "We analyzed the DAX-1 genes of two unrelated Japanese patients with congenital adrenal hypoplasia and hypogonadotropic hypogonadism using PCR amplification of genomic DNA and complete exonic sequencing, and established that congenital adrenal hypoplasia and hypogonadotropic hypogonadism result from not only inherited but also de novo mutation in the DAX-1 gene. " 04/01/1988 - "This detailed map is part of a less detailed map spanning 10 Mbp, also spanning the genes for glycerol kinase and congenital adrenal hypoplasia, constructed under electrophoresis conditions which separated DNA fragments in the range 200 to 4000 kbp. " 01/01/2014 - "DAX1 (dosage-sensitive sex reversal adrenal hypoplasia congenital critical region on X chromosome, gene 1), an atypical member of the nuclear receptor family due to lack of classical DNA-binding domains, has been known for its fundamental roles in the development, especially in the sex determination and steroidogenesis. "
9.	GonadotropinsIBA 10/01/1988 - "Gonadotropin deficiency as a significant association of complex glycerol kinase deficiency: a case report with cytogenetic and molecular-genetic studies." 10/01/1984 - "Congenital adrenal hypoplasia in a male with gonadotropin deficiency." 02/01/1982 - "In parallel with those previously reported, these two new cases show that the association between gonadotropin deficiency and congenital adrenal hypoplasia is not accidental, even if the relationship between the two components of the syndrome is still unclear." 02/01/2011 - "Gonadotropin-dependent precocious puberty in a patient with X-linked adrenal hypoplasia congenita caused by a novel DAX-1 mutation." 03/01/2007 - "Mutations in DAX1 (dosage-sensitive sex reversal-adrenal hypoplasia congenita critical region on the X chromosome gene 1; NR0B1) cause X-linked adrenal hypoplasia congenita, a disease characterized by primary adrenal failure, testicular dysgenesis, and gonadotropin deficiency. "
10.	3-Oxo-5-alpha-Steroid 4-Dehydrogenase (Testosterone 5 alpha Reductase)IBA 02/01/2020 - "DNA studies excluded gene alterations in sex-determining region Y (SRY), dosage-sensitive sex reversal-congenital adrenal hypoplasia critical region on the X chromosome protein 1 (DAX1), SRY-related high mobility group-box gene 9 (SOX9), nuclear receptor subfamily 5, group a, member 1 (NR5A1), nuclear receptor subfamily 3, group c, member 4 (NR3C4) and steroid 5-alpha-reductase 2 (SRD5A2). "

Therapies and Procedures

1.	Therapeutics 11/01/1995 - "We report on the diagnostics, the therapeutics and the follow-up (to 3 years and 5 months) of a newborn affected by X-linked congenital adrenal hypoplasia. " 12/01/1983 - "Prolonged survival without therapy in congenital adrenal hypoplasia." 12/01/1984 - "A patient with congenital adrenal hypoplasia (AH) and hypogonadotrophic hypogonadism was treated with pulsatile subcutaneous GnRH therapy for 16 weeks in an attempt to induce puberty. " 12/01/1984 - "Contrasting effects of subcutaneous pulsatile GnRH therapy in congenital adrenal hypoplasia and Kallmann's syndrome." 06/01/2021 - "He was diagnosed with X-linked adrenal hypoplasia congenita and then treated with human choriogonadotropin for the induction of spermatogenesis as well as with steroid replacement therapy."
2.	Ligation 01/01/2012 - "Multiplex ligation-dependent probe amplification analysis of the NR0B1(DAX1) locus enables explanation of phenotypic differences in patients with X-linked congenital adrenal hypoplasia."
3.	Anesthesia 10/01/2011 - "Anesthesia for a child suffering from a deletion in the Xp21 loci resulting in Duchenne disease, glycerol kinase deficiency, and congenital adrenal hypoplasia."
4.	Adrenalectomy 06/26/2019 - "The etiologies of the 49 cases were adrenoleukodystrophy (ALD; n = 22), X-linked adrenal hypoplasia congenital (X-AHC; n = 20), autoimmune polyglandular syndrome (APS; n = 3), triple A syndrome (n = 2), steroidogenic factor 1 (SF-1) gene mutation (n = 1) and adrenalectomy (n = 1). "