Abstract
Pulmonary arterial hypertension is characterised by the presence of pulmonary hypertension (mean pulmonary artery pressure > 25 mmHg at rest or >30 mmHg during exercise) and normal pulmonary wedge pressure (<12 mmHg). Several risk factors for pulmonary arterial hypertension have been described. In the absence of any factor or condition suspected to play a causal or facilitating role in the process, pulmonary hypertension is “unexplained” (primary pulmonary hypertension, PPH). PPH is a rare condition, with an estimated incidence of 2 per million people. Recent genetic studies have identified mutations in the bone morphogenetic protein receptor-II (BMPR-II) gene, a receptor member of the transforming growth factor-beta family, in a majority of familial cases of PPH. Interestingly, 25% of patients displaying sporadic PPH may also have mutations in theBMPR-II gene, emphasising the relevance of genetic susceptibility for this severe condition. Other molecular and biochemical processes behind the complex vascular changes associated with pulmonary arterial hypertension are currently investigated. Type 1a glycogen storage disease caused by a deficiency of glucose-6-phosphatase has an estimated incidence of 1 per 100,000 with a few reported cases of unexplained severe pulmonary hypertension. The occurrence of pulmonary arterial hypertension in type 1a glycogen storage disease could be due to vasoconstrictive amines such as serotonin, a pulmonary vasoconstrictor and growth factor for vascular smooth muscle cells stored in platelets.
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Abbreviations
- BMPR-II :
-
bone morphogenetic protein receptor-II
- PPH :
-
primary pulmonary hypertension
References
Abenhaim L, Humbert M (1999) Pulmonary hypertension related to drugs and toxins. Curr Opin Cardiol 14: 437–441
Bolz D, Stocker F, Zimmermann A (1996) Pulmonary vascular disease in a child with atrial septal defect of the secundum type and type I glycogen storage disease. Pediatr Cardiol 17: 265–267
Chen YT, Burchell A (1995) Glycogen storage disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D (eds) The metabolic and molecular bases of inherited disease, 7th edn. McGraw Hill, New York, pp. 935–965
Deng Z, Morse JH, Slager SL, Cuervo N, Moore KJ, Venetos G, Kalachnikov S, Cayanis E, Flischer SG, Barst RJ, Hodge SE, Knowles JA (2000) Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 67: 737–744
Furukawa N, Kinugasa A, Inoue F, Imashuku S., Takamatsu S, Sawasa T (1990) Type I glycogen storage disease with vasoconstrictive pulmonary hypertension. J Inherit Metab Dis 13: 102–107
Hamaoka K, Nakagawa M, Furukawa N, Sawada T (1990) Pulmonary hypertension in type I glycogen storage disease. Pediatr Cardiol 11: 54–56
Hervé P, Lebrec D, Brenot F, Simonneau G, Humbert M, Sitbon O, Duroux P (1998) Pulmonary vascular disorders in liver disease. Eur Respir J 11: 1153–1166
Humbert M, Sanchez O, Fartoukh M, Jagot J-L, Le Gall C, Sitbon O, Parent F, Simonneau G (1999) Short-term and long-term epoprostenol (prostacyclin) therapy in pulmonary hypertension secondary to connective tissue diseases: results of a pilot study. Eur Respir J 13: 1351–1356
Humbert M, Nunes H, Sitbon O, Parent F, Hervé P, Simonneau G (2001) Risk factors for pulmonary arterial hypertension. Clin Chest Med 22: 459–475
Humbert M, Labrune P, Sitbon O, Le Gall C, Callebert J, Hervé P, Samuel D, Machado R, Trembath R, Drouet L, Launay J-M, Simonneau G (2002) Pulmonary arterial hypertension and type I glycogen storage disease: the serotonin hypothesis. Eur Respir J 20: 59–65
Kishnani P, Bengur AR, Chen YT (1996) Pulmonary hypertension in glycogen storage disease type I. J Inherit Metab Dis 19: 213–216
Lane KB, Machado RD, Pauciulo MW, Thomson JR, Philipps III JA, Loyd JE, Nichols WC, Trembath RC (2000) Heterozygous germline mutations in a TGF-β receptor,BMPR2, are the cause of familial primary pulmonary hypertension. Nat Genet 26: 81–84
Lei KJ, Shelly LL, Pan CJ, Sidbury JB, Chou JY (1993) Mutations in the glucose-6-phosphatase gene that cause glycogen storage disease type Ia. Science 262: 580–583.
Lei KJ, Chen YT, Chen H (1995) Genetic basis of glycogen storage disease type Ia: prevalent mutations at the glucose-6-phosphatase locus. Am J Hum Genet 57: 766–771
Ohura T, Inoue CN, Abukawa D, Chiba AT, Tanaka T, Kakizawa H, Miyabayashi S, Igarashi Y, Iinuma K, Narisawa K (1995) Progressive pulmonary hypertension: a fatal complication of type I glycogen storage disease. J Inherit Metab Dis 18: 361–362
Petitpretz P, Brenot F, Azarian R, Parent F, Rain B, Hervé P, Simonneau G (1994) Pulmonary hypertension in patients with human immunodeficiency virus infection: comparison with primary pulmonary hypertension. Circulation 89: 2722–2727
Pizzo CJ (1980) Type I glycogen storage disease with focal nodular hyperplasia of the liver and vasoconstrictive pulmonary hypertension. Pediatrics 65: 341–343
Rubin LJ (1993) Primary pulmonary hypertension. Chest 104: 236–250
Thomson JR, Machado, RD, Pauciulo MW, Morgan NV, Humbert M, Elliott GC, Ward K, Yacoub M, Mikhail G, Rogers P, Newman J, Wheeler L, Higenbottam T, Gibbs JSR, Egan J, Crozier A, Peacock A, Allcock R, Corris P, Loyd JE, Trembath RC, Nichols WC (2000) Sporadic primary pulmonary hypertension is associated with germline mutations of the gene encoding BMPR-II, a receptor member of the TGF-β family. J Med Genet 37: 741–745
Voelkel NF, Tuder RM (1995) Cellular and molecular mechanisms in the pathogenesis of severe pulmonary hypertension. Eur Respir J 8: 2129–2138
Vongpatanasin W, Brickner E, Hillis D, Lange RA (1998) The Eisenmenger syndrome in adults. Ann Int Med 128: 745–755
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Published online: 31 July 2002
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Humbert, M., Labrune, P. & Simonneau, G. Severe pulmonary arterial hypertension in type 1 glycogen storage disease. Eur J Pediatr 161, S93–S96 (2002). https://doi.org/10.1007/BF02680003
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DOI: https://doi.org/10.1007/BF02680003