Details of Disease

General Information of Disease (ID: DISG873W)

• Disease Name: Congenital adrenal hyperplasia
• Synonyms: congenital lipoid adrenal hyperplasia; lipoid CAH; adrenal hyperplasia; adrenogenital syndrome; adrenogenital disorder; CAH; adrenal hyperplasia, congenital; congenital adrenal gland hyperplasia
• Disease Class: 5A71: Adrenogenital disorder
• Definition: Congenital adrenal hyperplasia (CAH) is an inherited endocrine disorder caused by a steroidogenic enzyme deficiency that is characterized by adrenal insufficiency and variable degrees of hyper or hypo androgeny manifestations, depending of the type and the severity of the disease.
• Disease Hierarchy:
  DIS19L71: Pediatric growth disorder
  DIS2N76U: Adrenogenital syndrome
  DIS7HNOH: Addison disease
  DISHIDRG: Steroid inherited metabolic disorder
  DISG873W: Congenital adrenal hyperplasia
• ICD Code:
  ICD-11: ICD-11: 5A71.01
  ICD-10: ICD-10: E25.0
  Expand ICD-11: '5A71.01
  Expand ICD-10: 'E25.0
• Disease Identifiers:
  MONDO ID: MONDO_0018479
  UMLS CUI: C0001627
  MedGen ID: 7900
  HPO ID: HP:0008258
  Orphanet ID: 418
  SNOMED CT ID: 237751000

Drug-Interaction Atlas (DIA) of This Disease

This Disease is Treated as An Indication in 9 Approved Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
Betamethasone	DMAHJEF	Approved	Small molecular drug	[1]
Cortisone Acetate	DMG8K57	Approved	Small molecular drug	[2]
Dexamethasone	DMMWZET	Approved	Small molecular drug	[3]
Fludrocortisone	DMUDIR8	Approved	Small molecular drug	[4]
Hydrocortisone	DMGEMB7	Approved	Small molecular drug	[5]
Methylprednisolone	DM4BDON	Approved	Small molecular drug	[6]
Prednisolone	DMQ8FR2	Approved	Small molecular drug	[7]
Prednisone	DM2HG4X	Approved	Small molecular drug	[8]
Triamcinolone	DM98IXF	Approved	Small molecular drug	[9]

This Disease is Treated as An Indication in 3 Clinical Trial Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
SSR125543	DMGJEB8	Phase 2	Small molecular drug	[10]
Tildacerfont	DMAB8LH	Phase 2	Small molecule	[11]
BBP-631	DMIAZFP	Phase 1/2	Gene therapy	[12]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 18 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
PRKAR1A	TTNAHEX	Limited	Biomarker	[13]
AVPR1A	TT4TFGN	Strong	Biomarker	[14]
AVPR2	TTK8R02	Strong	Biomarker	[14]
COASY	TT4YO0Z	Strong	Genetic Variation	[15]
CYP11B1	TTIQUX7	Strong	Genetic Variation	[16]
CYP11B2	TT9MNE2	Strong	Biomarker	[17]
CYP17A1	TTRA5BZ	Strong	Genetic Variation	[18]
CYP2B6	TTMH124	Strong	Genetic Variation	[19]
GIP	TT40HS5	Strong	Altered Expression	[20]
GLO1	TTV9A7R	Strong	Genetic Variation	[21]
HSD11B2	TT9H85R	Strong	Genetic Variation	[22]
HTR4	TT07C3Y	Strong	Biomarker	[14]
KCNJ5	TTEO25X	Strong	Genetic Variation	[23]
MC2R	TTPWFDX	Strong	Altered Expression	[24]
NR0B1	TTTK36V	Strong	Genetic Variation	[25]
STAR	TTEI40H	Strong	Genetic Variation	[26]
PDE11A	TTTWC79	Definitive	Genetic Variation	[27]
PRKACA	TT5U49F	Definitive	Genetic Variation	[28]

This Disease Is Related to 6 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
CHST3	DEQIZP2	Strong	Altered Expression	[29]
CYP3A7	DERD86B	Strong	Biomarker	[30]
CYP4F3	DEFCMPI	Strong	Genetic Variation	[31]
HSD3B1	DERDQWN	Strong	Biomarker	[32]
HSD3B2	DEN0GVQ	Strong	Genetic Variation	[33]
TGM5	DEW8QEH	Strong	Genetic Variation	[34]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
TNXB	OTVBWAV5	Limited	Biomarker	[35]
PDE8B	OT4217NK	moderate	Genetic Variation	[27]
ACADVL	OT50L4XB	Strong	Genetic Variation	[34]
ARMC5	OTO7IV74	Strong	Genetic Variation	[36]
EYS	OT0NBPL5	Strong	Genetic Variation	[34]
GRB7	OTF8Y9XY	Strong	Genetic Variation	[37]
HADHA	OTO557N2	Strong	Genetic Variation	[34]
MDH2	OT7364GY	Strong	Biomarker	[38]
OTOA	OTBTEFIE	Strong	Genetic Variation	[34]
PRKACB	OT6RMDCE	Strong	Genetic Variation	[39]
PROP1	OT8GF6N8	Strong	Genetic Variation	[34]

References

• [1] Betamethasone FDA Label
• [2] Cortisone acetate FDA Label
• [3] Dexamethasone FDA Label
• [4] Fludrocortisone FDA Label
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Methylprednisolone FDA Label
• [7] Prednisolone FDA Label
• [8] Prednisone FDA Label
• [9] Triamcinolone FDA Label
• [10] ClinicalTrials.gov (NCT04045145) Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of NBI-74788 in Pediatric Subjects With Congenital Adrenal Hyperplasia. U.S. National Institutes of Health.
• [11] ClinicalTrials.gov (NCT05370521) A Randomized, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety and Efficacy of Tildacerfont in Adult Subjects With Polycystic Ovary Syndrome (PCOS) and Elevated Adrenal Androgens. U.S.National Institutes of Health.
• [12] ClinicalTrials.gov (NCT04783181) A Phase 1/2, First-in-Human, Open-Label, Dose-Escalation Study of the Safety and Efficacy of Gene Therapy for Congenital Adrenal Hyperplasia Through Administration of an Adeno-Associated Virus (AAV) Serotype 5-Based Recombinant Vector Encoding the Human CYP21A2 Gene. U.S.National Institutes of Health.
• [13] Clinical features, diagnosis, treatment and molecular studies in paediatric Cushing's syndrome due to primary nodular adrenocortical hyperplasia.Clin Endocrinol (Oxf). 2004 Nov;61(5):553-9. doi: 10.1111/j.1365-2265.2004.02124.x.
• [14] Familial adrenocorticotropin-independent macronodular adrenal hyperplasia with aberrant serotonin and vasopressin adrenal receptors.Eur J Endocrinol. 2007 Jan;156(1):21-31. doi: 10.1530/eje.1.02324.
• [15] Activating mutation in the stimulatory guanine nucleotide-binding protein in an infant with Cushing's syndrome and nodular adrenal hyperplasia.J Clin Endocrinol Metab. 1994 Sep;79(3):890-3. doi: 10.1210/jcem.79.3.8077378.
• [16] A novel chimeric CYP11B2/CYP11B1 combined with a new p.L340P CYP11B1 mutation in a patient with 11OHD: case report.BMC Endocr Disord. 2018 Apr 27;18(1):23. doi: 10.1186/s12902-018-0249-z.
• [17] Aldosterone synthase deficiency and related disorders.Mol Cell Endocrinol. 2004 Mar 31;217(1-2):81-7. doi: 10.1016/j.mce.2003.10.013.
• [18] Steroid metabolism gene variants and their genotype-phenotype correlations in Chinese early-onset hypertension patients.Hypertens Res. 2019 Oct;42(10):1536-1543. doi: 10.1038/s41440-019-0306-7. Epub 2019 Aug 6.
• [19] Alternative pathway androgen biosynthesis and human fetal female virilization.Proc Natl Acad Sci U S A. 2019 Oct 29;116(44):22294-22299. doi: 10.1073/pnas.1906623116. Epub 2019 Oct 14.
• [20] The aberrant expression of the gastric inhibitory polypeptide (GIP) receptor in adrenal hyperplasia: does chronic adrenocorticotropin exposure stimulate up-regulation of GIP receptors in Cushing's disease?.J Clin Endocrinol Metab. 2005 May;90(5):3009-16. doi: 10.1210/jc.2004-0946. Epub 2005 Feb 10.
• [21] Sharing of MHC haplotypes among apparently unrelated patients with congenital adrenal hyperplasia due to 21-hydroxylase deficiency.Immunogenetics. 1987;25(2):99-103. doi: 10.1007/BF00364274.
• [22] Uniparental Isodisomy of Chromosome 1 Unmasking an Autosomal Recessive 3-Beta Hydroxysteroid Dehydrogenase Type II-Related Congenital Adrenal Hyperplasia.J Clin Res Pediatr Endocrinol. 2017 Mar 1;9(1):70-73. doi: 10.4274/jcrpe.3680. Epub 2016 Oct 31.
• [23] An Update on Familial Hyperaldosteronism.Horm Metab Res. 2015 Dec;47(13):941-6. doi: 10.1055/s-0035-1564166. Epub 2015 Oct 7.
• [24] Increased expression of ACTH (MC2R) and androgen (AR) receptors in giant bilateral myelolipomas from patients with congenital adrenal hyperplasia.BMC Endocr Disord. 2014 May 12;14:42. doi: 10.1186/1472-6823-14-42.
• [25] Primary adrenal insufficiency caused by a novel mutation in DAX1 gene.J Clin Res Pediatr Endocrinol. 2013;5(1):55-7. doi: 10.4274/Jcrpe.895.
• [26] Assisted Reproduction in Congenital Adrenal Hyperplasia.Front Endocrinol (Lausanne). 2019 Oct 23;10:723. doi: 10.3389/fendo.2019.00723. eCollection 2019.
• [27] Carney complex and other conditions associated with micronodular adrenal hyperplasias.Best Pract Res Clin Endocrinol Metab. 2010 Dec;24(6):907-14. doi: 10.1016/j.beem.2010.10.006.
• [28] PRKACA mutations in cortisol-producing adenomas and adrenal hyperplasia: a single-center study of 60 cases.Eur J Endocrinol. 2015 Jun;172(6):677-85. doi: 10.1530/EJE-14-1113. Epub 2015 Mar 6.
• [29] Congenital adrenal hyperplasia due to 3beta-hydroxysteroid dehydrogenase/Delta(5)-Delta(4) isomerase deficiency.Semin Reprod Med. 2002 Aug;20(3):255-76. doi: 10.1055/s-2002-35373.
• [30] Neonatal cytochrome P450 CYP3A7: A comprehensive review of its role in development, disease, and xenobiotic metabolism.Arch Biochem Biophys. 2019 Sep 30;673:108078. doi: 10.1016/j.abb.2019.108078. Epub 2019 Aug 22.
• [31] Deletion of the steroid 21-hydroxylase and complement C4 genes in congenital adrenal hyperplasia.J Med Genet. 1986 Jun;23(3):204-9. doi: 10.1136/jmg.23.3.204.
• [32] Refining hormonal diagnosis of type II 3beta-hydroxysteroid dehydrogenase deficiency in patients with premature pubarche and hirsutism based on HSD3B2 genotyping.J Clin Endocrinol Metab. 2005 Mar;90(3):1287-93. doi: 10.1210/jc.2004-1552. Epub 2004 Dec 7.
• [33] Non-Virilizing Congenital Adrenal Hyperplasia in a Female Patient with a Novel HSD3B2 Mutation.Sex Dev. 2016;10(4):200-204. doi: 10.1159/000448724. Epub 2016 Sep 15.
• [34] Exome-based search for recurrent disease-causing alleles in Russian population.Eur J Med Genet. 2019 Jul;62(7):103656. doi: 10.1016/j.ejmg.2019.04.013. Epub 2019 Apr 24.
• [35] High-Throughput Screening for CYP21A1P-TNXA/TNXB Chimeric Genes Responsible for Ehlers-Danlos Syndrome in Patients with Congenital Adrenal Hyperplasia.J Mol Diagn. 2019 Sep;21(5):924-931. doi: 10.1016/j.jmoldx.2019.06.001. Epub 2019 Jun 21.
• [36] A multicenter experience on the prevalence of ARMC5 mutations in patients with primary bilateral macronodular adrenal hyperplasia: from genetic characterization to clinical phenotype.Endocrine. 2017 Mar;55(3):959-968. doi: 10.1007/s12020-016-0956-z. Epub 2016 Apr 19.
• [37] The HLA-A3, Cw6,B47,DR7 extended haplotypes in salt losing 21-hydroxylase deficiency and in the Old Order Amish: identical class I antigens and class II alleles with at least two crossover sites in the class III region.Tissue Antigens. 1995 Sep;46(3 ( Pt 1)):163-72. doi: 10.1111/j.1399-0039.1995.tb03115.x.
• [38] PRECISION MEDICINE IN ADRENAL DISORDERS: THE NEXT GENERATION.Endocr Pract. 2017 Jun;23(6):672-679. doi: 10.4158/EP161716.RA. Epub 2017 Mar 23.
• [39] Carney complex: an update.Eur J Endocrinol. 2015 Oct;173(4):M85-97. doi: 10.1530/EJE-15-0209. Epub 2015 Jun 30.