Clinical features of pulmonary arterial hypertension in young people with an ALK1 mutation and hereditary haemorrhagic telangiectasia

Abstract

This report highlights ALK1 mutations associated with a variable PAH phenotype, including pulmonary arteriovenous malformations and severe PAH presenting early in life. Echocardiographic screening for elevated right ventricular pressure may be indicated in patients with HHT, particularly those with an identified ALK1 mutation. Clinical features or a family history of HHT should be elicited in children and adolescents with idiopathic PAH; ALK1 screening may be appropriate when such features are present.

Cardiopulmonary Exercise Testing Demonstrates Maintenance of Exercise Capacity in Patients With Hypoxemia and Pulmonary Arteriovenous Malformations

“…These findings have not been followed-up, due to a recent focus on pulmonary hypertension in the field, 12,[19][20][21][22][23][24][25][26][27] and in terms of prophylaxis.…”

“…3,6,7 The majority of PAVM patients have underlying hereditary hemorrhagic telangiectasia(HHT), 11,17,18 but overall, pulmonary hypertension is uncommon in PAVM/HHT patients. 12 When pulmonary hypertension does occur, 19,20 this results not from hypoxia, but from other pathophysiological processes, particularly pulmonary arterial hypertension, 12,[21][22][23][24] and pulmonary venous hypertension associated with hepatic AVMs and high outputs states. 12,[25][26][27] Our hypothesis was that in the presence of hypoxemia but absence of pulmonary hypertension, exercise capacity can be maintained by cardiovascular andhematological 28 adaptations.…”

Pulmonary Hypertension in a Large Cohort with Hereditary Hemorrhagic Telangiectasia

“…In 2001, it was demonstrated that different mutations in ACVRL1 predispose patients for the development of HPAH [14] . This association was confirmed in a few case series describing the presence of HPAH in patients with an ACVRL1 mutation and clinical features of HHT [8,14,15,[17][18][19] . Trembath et al [14] described that mutations in ACVRL1 may lead to occlusion of the pulmonary arteries, resulting in HPAH, together with vascular dilation, manifesting as AVMs in HHT.…”

Bilateral lung transplant for hereditary hemorrhagic telangiectasia in a pediatric patient

“…These patients may have severe cyanosis, desaturation with exercise, and embolic risk that may warrant surgical resection of the affected segment or lobe. Additional reports have noted progression in pulmonary hypertension in patients after embolization (7).…”

“…A thorough evaluation for any additional manifestations of HHT revealed only a history of rare epistaxis, but no evidence of CNS, hepatic, or other systemic manifestations. Several yr later, with the availability of clinical mutation analysis, the patient was consented for genetic screening through a protocol approved by the Children’s Hospital Committee on Clinical Investigation and found to have an ALK1 mutation (7).…”