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Paroxysmal nocturnal hemoglobinuria 2(PNH2)

MedGen UID:
815699
Concept ID:
C3809369
Disease or Syndrome
Synonym: PNH2
 
Gene (location): PIGT (20q13.12)
 
Monarch Initiative: MONDO:0014166
OMIM®: 615399

Definition

Any paroxysmal nocturnal hemoglobinuria in which the cause of the disease is a mutation in the PIGT gene. [from MONDO]

Clinical features

From HPO
Abdominal pain
MedGen UID:
7803
Concept ID:
C0000737
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.
Arthralgia
MedGen UID:
13917
Concept ID:
C0003862
Sign or Symptom
Joint pain.
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Paroxysmal nocturnal hemoglobinuria
MedGen UID:
7471
Concept ID:
C0024790
Disease or Syndrome
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired (not inherited) disorder that leads to the premature death and impaired production of blood cells. The disorder affects red blood cells (erythrocytes), which carry oxygen; white blood cells (leukocytes), which protect the body from infections; and platelets (thrombocytes), which are involved in blood clotting. PNH can occur at any age, although it is most often diagnosed in young adulthood.\n\nPeople with PNH have sudden, recurring episodes of symptoms (paroxysmal symptoms), which may be triggered by stresses on the body, such as infections or physical exertion. During these episodes, red blood cells are broken down earlier than they should be (hemolysis). Affected individuals may pass dark-colored urine because of the presence of hemoglobin, the oxygen-carrying protein in blood. The abnormal presence of hemoglobin in the urine is called hemoglobinuria. In many, but not all cases, hemoglobinuria is most noticeable early in the morning, upon passing urine that has accumulated in the bladder during the night (nocturnal).\n\nThe premature breakdown of red blood cells results in a shortage of these cells in the blood (hemolytic anemia), which can cause signs and symptoms such as fatigue, weakness, abnormally pale skin (pallor), shortness of breath, and an increased heart rate (tachycardia). People with PNH may also be prone to infections because of a shortage of white blood cells (leukopenia).\n\nAbnormal platelets associated with PNH can cause problems in the blood clotting process. As a result, people with this disorder may experience abnormal blood clotting (thrombosis), especially in large abdominal veins; or, less often, episodes of severe bleeding (hemorrhage).\n\nIndividuals with PNH are at increased risk of developing cancer in blood-forming cells (leukemia). In some cases, people who have or have been treated for another blood disease called aplastic anemia may develop PNH. In a small number of affected individuals, the signs and symptoms of PNH disappear on their own.\n\nA very rare form of PNH involves abnormal inflammation in addition to the typical features described above. Inflammation is a normal immune system response to injury and foreign invaders (such as bacteria). In people with this rare form of PNH, the immune response is turned on (activated) abnormally and can cause recurrent aseptic meningitis (which is inflammation of the membranes surrounding the brain and spinal cord that is not related to infection); a red, itchy rash (known as hives or urticaria); joint pain (arthralgia); or inflammatory bowel disease. The inflammatory disorders usually begin earlier than the blood cell problems.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Headache
MedGen UID:
9149
Concept ID:
C0018681
Sign or Symptom
Cephalgia, or pain sensed in various parts of the head, not confined to the area of distribution of any nerve.
Hemolytic anemia
MedGen UID:
1916
Concept ID:
C0002878
Disease or Syndrome
A type of anemia caused by premature destruction of red blood cells (hemolysis).
Dyspnea
MedGen UID:
3938
Concept ID:
C0013404
Sign or Symptom
Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale.

Professional guidelines

PubMed

Dingli D, Matos JE, Lehrhaupt K, Krishnan S, Yeh M, Fishman J, Sarda SP, Baver SB
Ann Hematol 2022 Feb;101(2):251-263. Epub 2022 Jan 1 doi: 10.1007/s00277-021-04715-5. PMID: 34973099Free PMC Article
Hill QA, Hill A, Berentsen S
Blood Adv 2019 Jun 25;3(12):1897-1906. doi: 10.1182/bloodadvances.2019000036. PMID: 31235526Free PMC Article
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology
Br J Haematol 2016 Jan;172(2):187-207. Epub 2015 Nov 16 doi: 10.1111/bjh.13853. PMID: 26568159

Recent clinical studies

Etiology

Peffault de Latour R, Röth A, Kulasekararaj AG, Han B, Scheinberg P, Maciejewski JP, Ueda Y, de Castro CM, Di Bona E, Fu R, Zhang L, Griffin M, Langemeijer SMC, Panse J, Schrezenmeier H, Barcellini W, Mauad VAQ, Schafhausen P, Tavitian S, Beggiato E, Chew LP, Gaya A, Huang WH, Jang JH, Kitawaki T, Kutlar A, Notaro R, Pullarkat V, Schubert J, Terriou L, Uchiyama M, Wong Lee Lee L, Yap ES, Sicre de Fontbrune F, Marano L, Alashkar F, Gandhi S, Trikha R, Yang C, Liu H, Kelly RJ, Höchsmann B, Kerloeguen C, Banerjee P, Levitch R, Kumar R, Wang Z, Thorburn C, Maitra S, Li S, Verles A, Dahlke M, Risitano AM
N Engl J Med 2024 Mar 14;390(11):994-1008. doi: 10.1056/NEJMoa2308695. PMID: 38477987
Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES
Blood Adv 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960. PMID: 35561315Free PMC Article
Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, Halkes CJM, Recher C, Barraco F, Forcade E, Vallejo JC, Drexler B, Mear JB, Smith AE, Angelucci E, Raymakers RAP, de Groot MR, Daguindau E, Nur E, Barcellini W, Russell NH, Terriou L, Iori AP, La Rocca U, Sureda A, Sánchez-Ortega I, Xicoy B, Jarque I, Cavenagh J, Sicre de Fontbrune F, Marotta S, Munir T, Tjon JML, Tavitian S, Praire A, Clement L, Rabian F, Marano L, Hill A, Palmisani E, Muus P, Cacace F, Frieri C, van Lint MT, Passweg JR, Marsh JCW, Socié G, Mufti GJ, Dufour C, Risitano AM; Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation
N Engl J Med 2022 Jan 6;386(1):11-23. doi: 10.1056/NEJMoa2109965. PMID: 34986284
Risitano AM, Peffault de Latour R
Br J Haematol 2022 Jan;196(2):288-303. Epub 2021 Aug 5 doi: 10.1111/bjh.17753. PMID: 34355382Free PMC Article
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article

Diagnosis

Risitano AM, Peffault de Latour R
Br J Haematol 2022 Jan;196(2):288-303. Epub 2021 Aug 5 doi: 10.1111/bjh.17753. PMID: 34355382Free PMC Article
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article
Schrezenmeier H, Röth A, Araten DJ, Kanakura Y, Larratt L, Shammo JM, Wilson A, Shayan G, Maciejewski JP
Ann Hematol 2020 Jul;99(7):1505-1514. Epub 2020 May 10 doi: 10.1007/s00277-020-04052-z. PMID: 32390114Free PMC Article
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology
Br J Haematol 2016 Jan;172(2):187-207. Epub 2015 Nov 16 doi: 10.1111/bjh.13853. PMID: 26568159
Brodsky RA
Blood 2014 Oct 30;124(18):2804-11. Epub 2014 Sep 18 doi: 10.1182/blood-2014-02-522128. PMID: 25237200Free PMC Article

Therapy

Jang JH, Wong L, Ko BS, Yoon SS, Li K, Baltcheva I, Nidamarthy PK, Chawla R, Junge G, Yap ES
Blood Adv 2022 Aug 9;6(15):4450-4460. doi: 10.1182/bloodadvances.2022006960. PMID: 35561315Free PMC Article
Peffault de Latour R, Kulasekararaj A, Iacobelli S, Terwel SR, Cook R, Griffin M, Halkes CJM, Recher C, Barraco F, Forcade E, Vallejo JC, Drexler B, Mear JB, Smith AE, Angelucci E, Raymakers RAP, de Groot MR, Daguindau E, Nur E, Barcellini W, Russell NH, Terriou L, Iori AP, La Rocca U, Sureda A, Sánchez-Ortega I, Xicoy B, Jarque I, Cavenagh J, Sicre de Fontbrune F, Marotta S, Munir T, Tjon JML, Tavitian S, Praire A, Clement L, Rabian F, Marano L, Hill A, Palmisani E, Muus P, Cacace F, Frieri C, van Lint MT, Passweg JR, Marsh JCW, Socié G, Mufti GJ, Dufour C, Risitano AM; Severe Aplastic Anemia Working Party of the European Society for Blood and Marrow Transplantation
N Engl J Med 2022 Jan 6;386(1):11-23. doi: 10.1056/NEJMoa2109965. PMID: 34986284
Brodsky RA
Blood 2021 Mar 11;137(10):1304-1309. doi: 10.1182/blood.2019003812. PMID: 33512400Free PMC Article
Singh S, Kumar NK, Dwiwedi P, Charan J, Kaur R, Sidhu P, Chugh VK
Curr Clin Pharmacol 2018;13(2):85-99. doi: 10.2174/1574884712666170809124728. PMID: 28799485
Killick SB, Bown N, Cavenagh J, Dokal I, Foukaneli T, Hill A, Hillmen P, Ireland R, Kulasekararaj A, Mufti G, Snowden JA, Samarasinghe S, Wood A, Marsh JC; British Society for Standards in Haematology
Br J Haematol 2016 Jan;172(2):187-207. Epub 2015 Nov 16 doi: 10.1111/bjh.13853. PMID: 26568159

Prognosis

de Latour RP, Szer J, Weitz IC, Röth A, Höchsmann B, Panse J, Usuki K, Griffin M, Kiladjian JJ, de Castro CM, Nishimori H, Ajayi T, Al-Adhami M, Deschatelets P, Francois C, Grossi F, Risitano AM, Hillmen P
Lancet Haematol 2022 Sep;9(9):e648-e659. doi: 10.1016/S2352-3026(22)00210-1. PMID: 36055332
Risitano AM, Peffault de Latour R
Br J Haematol 2022 Jan;196(2):288-303. Epub 2021 Aug 5 doi: 10.1111/bjh.17753. PMID: 34355382Free PMC Article
Sun L, Babushok DV
Blood 2020 Jul 2;136(1):36-49. doi: 10.1182/blood.2019000940. PMID: 32430502Free PMC Article
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A
Blood 2019 Feb 7;133(6):530-539. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876136. PMID: 30510080Free PMC Article
Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Röth A, Peffault de Latour R
Blood 2019 Feb 7;133(6):540-549. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876805. PMID: 30510079Free PMC Article

Clinical prediction guides

Wong RSM, Navarro-Cabrera JR, Comia NS, Goh YT, Idrobo H, Kongkabpan D, Gómez-Almaguer D, Al-Adhami M, Ajayi T, Alvarenga P, Savage J, Deschatelets P, Francois C, Grossi F, Dumagay T
Blood Adv 2023 Jun 13;7(11):2468-2478. doi: 10.1182/bloodadvances.2022009129. PMID: 36848639Free PMC Article
Schrezenmeier H, Röth A, Araten DJ, Kanakura Y, Larratt L, Shammo JM, Wilson A, Shayan G, Maciejewski JP
Ann Hematol 2020 Jul;99(7):1505-1514. Epub 2020 May 10 doi: 10.1007/s00277-020-04052-z. PMID: 32390114Free PMC Article
Röth A, Nishimura JI, Nagy Z, Gaàl-Weisinger J, Panse J, Yoon SS, Egyed M, Ichikawa S, Ito Y, Kim JS, Ninomiya H, Schrezenmeier H, Sica S, Usuki K, Sicre de Fontbrune F, Soret J, Sostelly A, Higginson J, Dieckmann A, Gentile B, Anzures-Cabrera J, Shinomiya K, Jordan G, Biedzka-Sarek M, Klughammer B, Jahreis A, Bucher C, Peffault de Latour R
Blood 2020 Mar 19;135(12):912-920. doi: 10.1182/blood.2019003399. PMID: 31978221Free PMC Article
Lee JW, Sicre de Fontbrune F, Wong Lee Lee L, Pessoa V, Gualandro S, Füreder W, Ptushkin V, Rottinghaus ST, Volles L, Shafner L, Aguzzi R, Pradhan R, Schrezenmeier H, Hill A
Blood 2019 Feb 7;133(6):530-539. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876136. PMID: 30510080Free PMC Article
Kulasekararaj AG, Hill A, Rottinghaus ST, Langemeijer S, Wells R, Gonzalez-Fernandez FA, Gaya A, Lee JW, Gutierrez EO, Piatek CI, Szer J, Risitano A, Nakao S, Bachman E, Shafner L, Damokosh AI, Ortiz S, Röth A, Peffault de Latour R
Blood 2019 Feb 7;133(6):540-549. Epub 2018 Dec 3 doi: 10.1182/blood-2018-09-876805. PMID: 30510079Free PMC Article

Recent systematic reviews

Garred P, Tenner AJ, Mollnes TE
Pharmacol Rev 2021 Apr;73(2):792-827. doi: 10.1124/pharmrev.120.000072. PMID: 33687995Free PMC Article
Tu J, Pan H, Li R, Wang Z, Lian Y, Li W, Shi J, Fang L
Acta Haematol 2021;144(1):34-43. Epub 2020 Sep 2 doi: 10.1159/000506387. PMID: 32877903
Hill QA, Hill A, Berentsen S
Blood Adv 2019 Jun 25;3(12):1897-1906. doi: 10.1182/bloodadvances.2019000036. PMID: 31235526Free PMC Article
Qi X, Wu F, He C, Fan D, Han G
Eur J Gastroenterol Hepatol 2015 Jan;27(1):77-83. doi: 10.1097/MEG.0000000000000221. PMID: 25426980
Martí-Carvajal AJ, Anand V, Cardona AF, Solà I
Cochrane Database Syst Rev 2014 Oct 30;(10):CD010340. doi: 10.1002/14651858.CD010340.pub2. PMID: 25356860

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