EIF2AK4 mutation in pulmonary veno-occlusive disease: A case report and review of the literature

• Published in: Medicine (Baltimore) 2016-09, Vol.95 (39), p.e5030-e5030
• Main Authors: Liang, Li, Ma, Guofeng, Chen, Kai, Liu, Yangxiang, Wu, Xiaohong, Ying, Kejing, Zhang, Ruifeng
• Format: Article
• Language: English
• Subjects: Adult; Clinical Case Report; DNA - genetics; DNA Mutational Analysis; Humans; Male; Mutation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Pulmonary Veno-Occlusive Disease - diagnosis; Pulmonary Veno-Occlusive Disease - genetics; Pulmonary Veno-Occlusive Disease - metabolism; Tomography, X-Ray Computed
• ISSN: 0025-7974; 1536-5964
• DOI: 10.1097/MD.0000000000005030

Pulmonary veno-occlusive disease (PVOD) is a rare and devastating cause of pulmonary arterial hypertension with a non-specific clinical presentation and a relatively specific presentation in high-resolution thoracic CT scan images. Definitive diagnosis is made by histological examination in previous. According to the 2015 ESC/ERS Guidelines, detection of a mutation in the eukaryotic translation initiation factor 2 alpha kinase 4 (EIF2AK4) without histological confirmation is recommended to validate the diagnosis of PVOD. We report the case of a 27-year-old man who was admitted for persistent cough and dyspnea that had lasted for 5 months and had developed and experienced progressive dyspnea for the last 2 months. The echocardiogram and right heart catheterization without vasodilator challenge confirmed the diagnosis of pulmonary arterial hypertension. Other tests, such as high-resolution thoracic CT scan, V/Q scan, pulmonary function test with diffusion capacity, and blood tests, excluded other associated diseases which could have caused pulmonary hypertension. The initial diagnosis at admission was idiopathic pulmonary arterial hypertension and an oral vasodilator (sildenafil) was given. However, the dyspnea subsequently worsened, and the patient was transferred to a regional lung transplant center, where he died of heart failure 1 week later. Using exome sequencing, we found an EIF2AK4 mutation, which was sufficient to confirm the diagnosis of PVOD. This is the first reported case of EIF2AK4 mutation in PVOD in a Chinese patient population. We found the frameshift EIF2AK4 mutation c.1392delT (p.Arg465fs) in this case. Up to now, there has been a paucity of data on this rare disease, and the exact role of EIF2AK4 loss-of-function mutations in the pathogenesis of PVOD is still unknown. More investigations should be conducted in the future.