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Pulmonary hypertension, primary, autosomal recessive(PPH5)

MedGen UID:
1802382
Concept ID:
C5676877
Disease or Syndrome
Synonyms: PPH5; PULMONARY HYPERTENSION, PRIMARY, 5; PULMONARY HYPERTENSION, PRIMARY, 5, AUTOSOMAL RECESSIVE
 
Gene (location): ATP13A3 (3q29)
 
Monarch Initiative: MONDO:0009935
OMIM®: 265400

Definition

Primary pulmonary hypertension-5 (PPH5) is an autosomal recessive disorder characterized by the onset of pulmonary arterial hypertension in infancy, resulting in right heart dysfunction and ultimately right heart failure. Death in early childhood is common (Machado et al., 2022). For a discussion of genetic heterogeneity of primary pulmonary hypertension, see PPH1 (178600). [from OMIM]

Clinical features

From HPO
Fatigue
MedGen UID:
41971
Concept ID:
C0015672
Sign or Symptom
A subjective feeling of tiredness characterized by a lack of energy and motivation.
Angina pectoris
MedGen UID:
1929
Concept ID:
C0002962
Sign or Symptom
Paroxysmal chest pain that occurs with exertion or stress and is related to myocardial ischemia.
Syncope
MedGen UID:
21443
Concept ID:
C0039070
Sign or Symptom
Syncope is a syndrome in which loss of consciousness is of relatively sudden onset, temporary (usually less than 1 to 2 minutes), self-terminating, and of usually rapid recovery. Syncope leads to a generalized weakness of muscles with loss of postural tone, inability to stand upright, and loss of consciousness. Once the patient is in a horizontal position, blood flow to the brain is no longer hindered by gravitation and consciousness is regained. Unconsciousness usually lasts for seconds to minutes. Headache and drowsiness (which usually follow seizures) do not follow a syncopal attack. Syncope results from a sudden impairment of brain metabolism usually due to a reduction in cerebral blood flow.
Right ventricular hypertrophy
MedGen UID:
57981
Concept ID:
C0162770
Disease or Syndrome
In this case the right ventricle is more muscular than normal, causing a characteristic boot-shaped (coeur-en-sabot) appearance as seen on anterior- posterior chest x-rays. Right ventricular hypertrophy is commonly associated with any form of right ventricular outflow obstruction or pulmonary hypertension, which may in turn owe its origin to left-sided disease. The echocardiographic signs are thickening of the anterior right ventricular wall and the septum. Cavity size is usually normal, or slightly enlarged. In many cases there is associated volume overload present due to tricuspid regurgitation, in the absence of this, septal motion is normal.
Right ventricular failure
MedGen UID:
65907
Concept ID:
C0235527
Disease or Syndrome
Reduced ability of the right ventricle to perform its function (to receive blood from the right atrium and to eject blood into the pulmonary artery), often leading to pitting peripheral edema, ascites, and hepatomegaly.
Pulmonary arterial hypertension
MedGen UID:
425404
Concept ID:
C2973725
Disease or Syndrome
Pulmonary hypertension is defined mean pulmonary artery pressure of 25mmHg or more and pulmonary capillary wedge pressure of 15mmHg or less when measured by right heart catheterisation at rest and in a supine position.
Easy fatigability
MedGen UID:
373253
Concept ID:
C1837098
Finding
Increased susceptibility to fatigue.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Exertional dyspnea
MedGen UID:
68549
Concept ID:
C0231807
Sign or Symptom
Perceived difficulty to breathe that occurs with exercise or exertion and improves with rest.

Recent clinical studies

Etiology

Machado RD, Welch CL, Haimel M, Bleda M, Colglazier E, Coulson JD, Debeljak M, Ekstein J, Fineman JR, Golden WC, Griffin EL, Hadinnapola C, Harris MA, Hirsch Y, Hoover-Fong JE, Nogee L, Romer LH, Vesel S; NIHR Bioresource – Rare Diseases, Gräf S, Morrell NW, Southgate L, Chung WK
J Med Genet 2022 Sep;59(9):906-911. Epub 2021 Sep 7 doi: 10.1136/jmedgenet-2021-107831. PMID: 34493544Free PMC Article
Girerd B, Weatherald J, Montani D, Humbert M
Eur Respir Rev 2017 Sep 30;26(145) Epub 2017 Sep 6 doi: 10.1183/16000617.0037-2017. PMID: 28877973Free PMC Article
Girerd B, Lau E, Montani D, Humbert M
Curr Opin Pulm Med 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414. PMID: 28661905
Best DH, Austin ED, Chung WK, Elliott CG
Curr Opin Cardiol 2014 Nov;29(6):520-7. doi: 10.1097/HCO.0000000000000105. PMID: 25159282
Basel-Vanagaite L, Kornreich L, Schiller O, Yacobovich J, Merlob P
Am J Med Genet A 2008 Feb 15;146A(4):532-7. doi: 10.1002/ajmg.a.32135. PMID: 18203163

Diagnosis

Girerd B, Weatherald J, Montani D, Humbert M
Eur Respir Rev 2017 Sep 30;26(145) Epub 2017 Sep 6 doi: 10.1183/16000617.0037-2017. PMID: 28877973Free PMC Article
Girerd B, Lau E, Montani D, Humbert M
Curr Opin Pulm Med 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414. PMID: 28661905
Best DH, Austin ED, Chung WK, Elliott CG
Curr Opin Cardiol 2014 Nov;29(6):520-7. doi: 10.1097/HCO.0000000000000105. PMID: 25159282
Banka S, Newman WG
Orphanet J Rare Dis 2013 Jun 13;8:84. doi: 10.1186/1750-1172-8-84. PMID: 23758768Free PMC Article
Basel-Vanagaite L, Kornreich L, Schiller O, Yacobovich J, Merlob P
Am J Med Genet A 2008 Feb 15;146A(4):532-7. doi: 10.1002/ajmg.a.32135. PMID: 18203163

Therapy

Erol N, Yıldız M, Güven A, Yıldırım A
J Pediatr Endocrinol Metab 2018 Jun 27;31(6):675-679. doi: 10.1515/jpem-2017-0473. PMID: 29750649
Datta G, Dastidar DG, Kundu S, Datta B, Dastidar NG, Bannerjee A
J Assoc Physicians India 2011 Nov;59:738-40. PMID: 22616346
Lotan D, Eisenkraft A, Jacobsson JM, Bar-Yosef O, Kleta R, Gal N, Raviv-Zilka L, Gore H, Anikster Y
Pediatr Nephrol 2006 Mar;21(3):423-6. Epub 2005 Dec 29 doi: 10.1007/s00467-005-2125-0. PMID: 16382316
Yoshikawa S, Ikeda K, Kudo T, Kobayashi T
Auris Nasus Larynx 2004 Dec;31(4):361-8. doi: 10.1016/j.anl.2004.07.007. PMID: 15571908
Langleben D, Heneghan JM, Batten AP, Wang NS, Fitch N, Schlesinger RD, Guerraty A, Rouleau JL
Ann Intern Med 1988 Jul 15;109(2):106-9. doi: 10.7326/0003-4819-109-2-106. PMID: 3382104

Prognosis

Machado RD, Welch CL, Haimel M, Bleda M, Colglazier E, Coulson JD, Debeljak M, Ekstein J, Fineman JR, Golden WC, Griffin EL, Hadinnapola C, Harris MA, Hirsch Y, Hoover-Fong JE, Nogee L, Romer LH, Vesel S; NIHR Bioresource – Rare Diseases, Gräf S, Morrell NW, Southgate L, Chung WK
J Med Genet 2022 Sep;59(9):906-911. Epub 2021 Sep 7 doi: 10.1136/jmedgenet-2021-107831. PMID: 34493544Free PMC Article
Andijani AA, Shajira ES, Abushaheen A, Al-Matary A
Am J Case Rep 2019 Mar 18;20:354-360. doi: 10.12659/AJCR.912873. PMID: 30880327Free PMC Article
Girerd B, Weatherald J, Montani D, Humbert M
Eur Respir Rev 2017 Sep 30;26(145) Epub 2017 Sep 6 doi: 10.1183/16000617.0037-2017. PMID: 28877973Free PMC Article
Girerd B, Lau E, Montani D, Humbert M
Curr Opin Pulm Med 2017 Sep;23(5):386-391. doi: 10.1097/MCP.0000000000000414. PMID: 28661905
Basel-Vanagaite L, Kornreich L, Schiller O, Yacobovich J, Merlob P
Am J Med Genet A 2008 Feb 15;146A(4):532-7. doi: 10.1002/ajmg.a.32135. PMID: 18203163

Clinical prediction guides

Machado RD, Welch CL, Haimel M, Bleda M, Colglazier E, Coulson JD, Debeljak M, Ekstein J, Fineman JR, Golden WC, Griffin EL, Hadinnapola C, Harris MA, Hirsch Y, Hoover-Fong JE, Nogee L, Romer LH, Vesel S; NIHR Bioresource – Rare Diseases, Gräf S, Morrell NW, Southgate L, Chung WK
J Med Genet 2022 Sep;59(9):906-911. Epub 2021 Sep 7 doi: 10.1136/jmedgenet-2021-107831. PMID: 34493544Free PMC Article
Erol N, Yıldız M, Güven A, Yıldırım A
J Pediatr Endocrinol Metab 2018 Jun 27;31(6):675-679. doi: 10.1515/jpem-2017-0473. PMID: 29750649
Girerd B, Weatherald J, Montani D, Humbert M
Eur Respir Rev 2017 Sep 30;26(145) Epub 2017 Sep 6 doi: 10.1183/16000617.0037-2017. PMID: 28877973Free PMC Article
Tenorio J, Navas P, Barrios E, Fernández L, Nevado J, Quezada CA, López-Meseguer M, Arias P, Mena R, Lobo JL, Alvarez C, Heath K, Escribano-Subías P, Lapunzina P
Clin Genet 2015 Dec;88(6):579-83. Epub 2015 Jan 7 doi: 10.1111/cge.12549. PMID: 25512148
Yoshikawa S, Ikeda K, Kudo T, Kobayashi T
Auris Nasus Larynx 2004 Dec;31(4):361-8. doi: 10.1016/j.anl.2004.07.007. PMID: 15571908

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