Details of Disease

General Information of Disease (ID: DISNMXY8)

• Disease Name: X-linked adrenal hypoplasia congenita
• Synonyms: X-linked AHC; Addison disease, X-linked; adrenal insufficiency, progressive, and hypogonadotropic hypogonadism; AHC with HHG; adrenal hypoplasia, congenital, with precocious puberty; AHC with isolated gonadotropin deficiency; adrenal hypoplasia, congenital, with hypogonadotropic hypogonadism; adrenal hypoplasia, congenital; cytomegalic adrenocortical hypoplasia; cytomegalic congenital adrenal hypoplasia; mineralocorticoid deficiency, isolated; adrenal hypoplasia congenita; AHC; congenital adrenal hypoplasia; adrenal hypoplasia, congenital, X-linked recessive; X-linked congenital adrenal hypoplasia; X-linked adrenal hypoplasia congenita
• Definition: A X-linked condition characterized by underdevelopment of the adrenal gland and adrenal insufficiency caused by mutation(s) in the NR0B1 gene, resulting in decreased activity of the nuclear receptor protein DAX1, which may be associated with hypogonadotropic hypogonadism.
• Disease Hierarchy:
  DISB31JE: Alternating hemiplegia of childhood
  DIS2BIP8: Congenital nervous system disorder
  DISEV092: Congenital hypogonadotropic hypogonadism
  DIS3PN9X: X-linked disease
  DIS7HNOH: Addison disease
  DISNMXY8: X-linked adrenal hypoplasia congenita
• Disease Identifiers:
  MONDO ID: MONDO_0010264
  MESH ID: D000075262
  UMLS CUI: C0342482
  OMIM ID: 300200
  MedGen ID: 87442
  Orphanet ID: 95702
  SNOMED CT ID: 237764004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 16 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
ALDH3A2	TTB6UM0	Limited	Genetic Variation	[1]
CHAT	TTKYFSB	Limited	Biomarker	[2]
CYP11B1	TTIQUX7	Limited	Altered Expression	[3]
IL1RAP	TTWS50K	Limited	Biomarker	[4]
PCSK1	TTED9LZ	Limited	Genetic Variation	[5]
DMD	TTWLFXU	moderate	Genetic Variation	[6]
ATP1A2	TT5B6HJ	Strong	Genetic Variation	[7]
CACNA1A	TTX4QDJ	Strong	Genetic Variation	[8]
ESRRB	TTKF0XS	Strong	Genetic Variation	[9]
GNRHR	TT8R70G	Strong	Biomarker	[10]
MC2R	TTPWFDX	Strong	Genetic Variation	[11]
NNT	TTKIH76	Strong	Biomarker	[12]
NR0B1	TTTK36V	Strong	Genetic Variation	[13]
OTC	TT5KIO9	Strong	Biomarker	[14]
STAR	TTEI40H	Strong	Biomarker	[15]
NR0B1	TTTK36V	Definitive	X-linked	[16]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
GPT	DER5HFI	moderate	Altered Expression	[17]

This Disease Is Related to 15 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
ACD	OTC54EPO	Limited	Genetic Variation	[18]
HESX1	OT5E2Z4G	Limited	Altered Expression	[10]
IL1RAPL1	OTW3T4B2	Limited	Genetic Variation	[4]
MAGEB1	OTN7G8V1	Limited	Genetic Variation	[19]
NR2F2	OTJFS67N	Limited	Biomarker	[20]
ATP1A3	OTM8EG6H	moderate	Genetic Variation	[21]
GK	OTK2YRA0	moderate	Genetic Variation	[22]
MCM4	OT19PNNG	moderate	Biomarker	[23]
SERPINA4	OTBK0GG7	moderate	Genetic Variation	[24]
ANOS1	OTZJT4KN	Strong	Altered Expression	[25]
MPZ	OTAR2YXH	Strong	Biomarker	[26]
NR5A1	OTOULYR4	Strong	Biomarker	[15]
PMP22	OTXWYWCZ	Strong	Biomarker	[26]
PROP1	OT8GF6N8	Strong	Biomarker	[25]
NR0B1	OTC8P9GN	Definitive	X-linked	[16]

References

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• [4] Mental retardation in a boy with congenital adrenal hypoplasia: a clue to contiguous gene syndrome involving DAX1 and IL1RAPL.Endocr J. 2003 Jun;50(3):303-7. doi: 10.1507/endocrj.50.303.
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• [9] DAX1 and X-linked adrenal hypoplasia congenita: clinical and molecular analysis in five patients.Eur J Endocrinol. 2006 May;154(5):685-9. doi: 10.1530/eje.1.02132.
• [10] Advances in the molecular genetics of hypogonadotropic hypogonadism.J Pediatr Endocrinol Metab. 2001 Jan;14(1):3-15. doi: 10.1515/jpem.2001.14.1.3.
• [11] Familial glucocorticoid deficiency type 2: a case report.J Clin Res Pediatr Endocrinol. 2010;2(3):122-5. doi: 10.4274/jcrpe.v2i3.122. Epub 2010 Aug 6.
• [12] A novel homozygous mutation of the nicotinamide nucleotide transhydrogenase gene in a Japanese patient with familial glucocorticoid deficiency.Endocr J. 2013;60(7):855-9. doi: 10.1507/endocrj.ej13-0024. Epub 2013 Mar 9.
• [13] Gonadotropin- and Adrenocorticotropic Hormone-Independent Precocious Puberty of Gonadal Origin in a Patient with Adrenal Hypoplasia Congenita Due to DAX1 Gene Mutation - A Case Report and Review of the Literature: Implications for the Pathomechanism.Horm Res Paediatr. 2019;91(5):336-345. doi: 10.1159/000495189. Epub 2018 Dec 11.
• [14] Complex glycerol kinase deficiency: molecular-genetic, cytogenetic, and clinical studies of five Japanese patients.Am J Med Genet. 1988 Nov;31(3):603-16. doi: 10.1002/ajmg.1320310315.
• [15] Seven novel DAX1 mutations with loss of function identified in Chinese patients with congenital adrenal hypoplasia.J Clin Endocrinol Metab. 2010 Sep;95(9):E104-11. doi: 10.1210/jc.2009-2408. Epub 2010 Jun 23.
• [16] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [17] Role of IL28B gene polymorphism and cell-mediated immunity in spontaneous resolution of acute hepatitis C.Clin Infect Dis. 2013 Sep;57(6):803-11. doi: 10.1093/cid/cit402. Epub 2013 Jun 19.
• [18] IMAGe association and congenital adrenal hypoplasia: no disease-causing mutations found in the ACD gene.Mol Genet Metab. 2006 May;88(1):66-70. doi: 10.1016/j.ymgme.2006.01.006. Epub 2006 Feb 28.
• [19] Isolation and characterization of a MAGE gene family in the Xp21.3 region.Proc Natl Acad Sci U S A. 1995 May 23;92(11):4987-91. doi: 10.1073/pnas.92.11.4987.
• [20] Minireview: role of orphan nuclear receptors in cancer and potential as drug targets.Mol Endocrinol. 2014 Feb;28(2):157-72. doi: 10.1210/me.2013-1291. Epub 2013 Dec 2.
• [21] ATP1A3 mosaicism in families with alternating hemiplegia of childhood.Clin Genet. 2019 Jul;96(1):43-52. doi: 10.1111/cge.13539. Epub 2019 Apr 3.
• [22] A case of X-linked adrenal hypoplasia congenita, central precocious puberty and absence of the DAX-1 gene: implications for pubertal regulation.Horm Res. 2009;71(5):298-304. doi: 10.1159/000208804. Epub 2009 Apr 1.
• [23] MCM4 mutation causes adrenal failure, short stature, and natural killer cell deficiency in humans.J Clin Invest. 2012 Mar;122(3):814-20. doi: 10.1172/JCI60224. Epub 2012 Feb 22.
• [24] Genetics of hypogonadotropic hypogonadism.J Endocrinol Invest. 2000 Oct;23(9):560-5. doi: 10.1007/BF03343776.
• [25] Hypogonadotropic hypogonadism.Semin Reprod Med. 2002 Nov;20(4):327-38. doi: 10.1055/s-2002-36707.
• [26] Three novel mutations and a de novo deletion mutation of the DAX-1 gene in patients with X-linked adrenal hypoplasia congenita.J Clin Endocrinol Metab. 1997 Nov;82(11):3835-41. doi: 10.1210/jcem.82.11.4342.