Details of Disease

General Information of Disease (ID: DIS80J7E)

• Disease Name: Acute intermittent hepatic porphyria
• Synonyms: porphyria, acute intermittent; porphyria, Chester type; PBGD deficiency; HMBS deficiency; porphobilinogen deaminase deficiency; hydroxymethylbilane synthase deficiency; uroporphyrinogen synthase deficiency; porphyria, Swedish type; AIP; porphyria, acute intermittent, Nonerythroid variant; UPS deficiency; pyrroloporphyria; porphyria intermittent acute; AIP - acute intermittent porphyria; acute intermittent porphyria
• Disease Class: 5C58: Inborn porphyrin/heme metabolism error
• Definition: Acute intermittent porphyria is the most frequent and the most severe form of the acute hepatic porphyrias. It is characterized by the occurrence of neuro-visceral attacks without cutaneous manifestations.
• Disease Hierarchy:
  DISMI8EV: Hepatic porphyria
  DISBV50J: Acute disease
  DISEPFG2: Inherited porphyria
  DIS80J7E: Acute intermittent hepatic porphyria
• ICD Code:
  ICD-11: ICD-11: 5C58.11
  ICD-10: ICD-10: E80.21
• Disease Identifiers:
  MONDO ID: MONDO_0008294
  MESH ID: D017118
  UMLS CUI: C0162565
  OMIM ID: 176000
  MedGen ID: 56452
  Orphanet ID: 79276
  SNOMED CT ID: 234422006

Drug-Interaction Atlas (DIA) of This Disease

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

Drug Name	Drug ID	Highest Status	Drug Type	REF
Chlorpromazine	DMBGZI3	Approved	Small molecular drug	[1]
Givosiran	DM5PFIJ	Approved	Small interfering RNA	[2]
Promazine	DMZAL7W	Approved	Small molecular drug	[3]

This Disease is Treated as An Indication in 1 Investigative Drug(s)

Drug Name	Drug ID	Highest Status	Drug Type	REF
AMT-021	DMNKQZI	Investigative	NA	[4]

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 15 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
AMY2A	TTCGSZ4	Limited	Biomarker	[5]
HSPE1	TTWYMFE	Limited	Biomarker	[6]
LTBR	TTFO0PM	Limited	Altered Expression	[7]
ALAD	TTJHKYD	Strong	Biomarker	[8]
ALAS1	TTG1FXO	Strong	Biomarker	[9]
APOA2	TTGQA9W	Strong	Biomarker	[10]
CALCB	TTUZ9GV	Strong	Genetic Variation	[11]
CELA1	TT3NKIB	Strong	Biomarker	[12]
CXCR5	TTIW59R	Strong	Biomarker	[13]
FECH	TTQ6VF4	Strong	Genetic Variation	[14]
KCNA3	TTY3UE6	Strong	Genetic Variation	[15]
PRSS1	TT2WR1T	Strong	Genetic Variation	[11]
SLC15A2	TT27Q3A	Strong	Biomarker	[16]
HMBS	TTT0HW3	Definitive	Semidominant	[17]
PPOX	TTNFMS9	Definitive	Altered Expression	[18]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
ALAS2	DE437BY	Strong	Altered Expression	[19]

This Disease Is Related to 11 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
SKI	OT4KJ8F6	Limited	Altered Expression	[20]
ABCF1	OT6Q079J	Strong	Biomarker	[21]
AIP	OTDJ3OSV	Strong	Biomarker	[22]
ATP8	OTYQQR53	Strong	Genetic Variation	[23]
DEGS1	OT4WXPKW	Strong	Biomarker	[24]
DOCK3	OTF3YS2W	Strong	Biomarker	[25]
FCRL3	OTIFXFWL	Strong	Genetic Variation	[26]
KNTC1	OTI2OOFN	Strong	Biomarker	[27]
MED1	OTOO24C4	Strong	Biomarker	[25]
SPINK1	OTSUVAL2	Strong	Genetic Variation	[28]
HMBS	OT3P47DC	Definitive	Semidominant	[17]

References

• [1] Chlorpromazine FDA Label
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [3] Promazine FDA Label
• [4] The ChEMBL database in 2017. Nucleic Acids Res. 2017 Jan 4;45(D1):D945-D954.
• [5] Amylase alpha-2A autoantibodies: novel marker of autoimmune pancreatitis and fulminant type 1 diabetes.Diabetes. 2009 Mar;58(3):732-7. doi: 10.2337/db08-0493. Epub 2008 Nov 10.
• [6] HSP 10 is a new autoantigen in both autoimmune pancreatitis and fulminant type 1 diabetes.Biochem Biophys Res Commun. 2009 Aug 14;386(1):192-6. doi: 10.1016/j.bbrc.2009.06.009. Epub 2009 Jun 9.
• [7] The role of lymphotoxin signaling in the development of autoimmune pancreatitis and associated secondary extra-pancreatic pathologies.Cytokine Growth Factor Rev. 2014 Apr;25(2):125-37. doi: 10.1016/j.cytogfr.2014.01.003. Epub 2014 Jan 10.
• [8] The cutaneous porphyrias.Semin Cutan Med Surg. 1999 Dec;18(4):285-92. doi: 10.1016/s1085-5629(99)80027-3.
• [9] Leading RNA Interference Therapeutics Part 2: Silencing Delta-Aminolevulinic Acid Synthase 1, with a Focus on Givosiran.Mol Diagn Ther. 2020 Feb;24(1):61-68. doi: 10.1007/s40291-019-00438-6.
• [10] Serum apolipoprotein A2 isoforms in autoimmune pancreatitis.Biochem Biophys Res Commun. 2018 Mar 11;497(3):903-907. doi: 10.1016/j.bbrc.2018.02.170. Epub 2018 Feb 23.
• [11] CALCB splice region pathogenic variants leading to plasma cell neurotropic enrichment in type 1 autoimmune pancreatitis.Cell Death Dis. 2017 Feb 2;8(2):e2591. doi: 10.1038/cddis.2017.32.
• [12] Development of autoimmune pancreatitis is independent of CDKN1A/p21-mediated pancreatic inflammation.Gut. 2018 Sep;67(9):1663-1673. doi: 10.1136/gutjnl-2016-313458. Epub 2017 Aug 3.
• [13] Activated T-Follicular Helper 2 Cells Are Associated With Disease Activity in IgG4-Related Sclerosing Cholangitis and Pancreatitis.Clin Transl Gastroenterol. 2019 Apr;10(4):e00020. doi: 10.14309/ctg.0000000000000020.
• [14] Molecular characterization of porphyrias in Italy: a diagnostic flow-chart.Cell Mol Biol (Noisy-le-grand). 2002 Dec;48(8):867-76.
• [15] Polymorphism in the KCNA3 gene is associated with susceptibility to autoimmune pancreatitis in the Japanese population.Dis Markers. 2011;31(4):223-9. doi: 10.3233/DMA-2011-0820.
• [16] A Variant of Peptide Transporter 2 Predicts the Severity of Porphyria-Associated Kidney Disease.J Am Soc Nephrol. 2017 Jun;28(6):1924-1932. doi: 10.1681/ASN.2016080918. Epub 2016 Dec 28.
• [17] 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.
• [18] Biallelic inactivation of protoporphyrinogen oxidase and hydroxymethylbilane synthase is associated with liver cancer in acute porphyrias.J Hepatol. 2015 Mar;62(3):734-8. doi: 10.1016/j.jhep.2014.11.029. Epub 2014 Nov 28.
• [19] Circadian rhythms in acute intermittent porphyria--a pilot study.Eur J Clin Invest. 2013 Jul;43(7):727-39. doi: 10.1111/eci.12102. Epub 2013 May 8.
• [20] Promoter hypomethylation of SKI in autoimmune pancreatitis.Pathol Res Pract. 2018 Apr;214(4):492-497. doi: 10.1016/j.prp.2018.03.005. Epub 2018 Mar 6.
• [21] Two critical genes (HLA-DRB1 and ABCF1)in the HLA region are associated with the susceptibility to autoimmune pancreatitis.Immunogenetics. 2007 Jan;59(1):45-52. doi: 10.1007/s00251-006-0178-2. Epub 2006 Nov 21.
• [22] AIP and MEN1 mutations and AIP immunohistochemistry in pituitary adenomas in a tertiary referral center.Endocr Connect. 2019 Apr;8(4):338-348. doi: 10.1530/EC-19-0027.
• [23] The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.PLoS One. 2014 Jul 10;9(7):e102266. doi: 10.1371/journal.pone.0102266. eCollection 2014.
• [24] Qualitative and quantitative evaluation for morphological changes of the splenic artery in autoimmune pancreatitis: novel imaging findings for differentiation from pancreatic adenocarcinoma.Abdom Radiol (NY). 2018 Dec;43(12):3357-3366. doi: 10.1007/s00261-018-1634-9.
• [25] No evidence to support a role for Helicobacter pylori infection and plasminogen binding protein in autoimmune pancreatitis and IgG4-related disease in a UK cohort.Pancreatology. 2017 May-Jun;17(3):395-402. doi: 10.1016/j.pan.2017.04.002. Epub 2017 Apr 5.
• [26] Association of autoimmune pancreatitis with cytotoxic T-lymphocyte antigen 4 gene polymorphisms in Japanese patients.Am J Gastroenterol. 2008 Mar;103(3):588-94. doi: 10.1111/j.1572-0241.2007.01750.x.
• [27] Frequency and distribution of CD4+CXCR5+ follicular B helper Tcells within involved tissues in IgG4related ophthalmic disease.Mol Med Rep. 2017 Dec;16(6):9512-9520. doi: 10.3892/mmr.2017.7780. Epub 2017 Oct 12.
• [28] Human cationic trypsinogen but not serine peptidase inhibitor, Kazal type 1 variants increase the risk of type 1 autoimmune pancreatitis.J Gastroenterol Hepatol. 2014 Dec;29(12):2038-42. doi: 10.1111/jgh.12649.