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Original Research: Diffuse Lung Disease |

Hepatopulmonary Syndrome Is a Frequent Cause of Dyspnea in the Short Telomere DisordersHepatopulmonary Syndrome in Telomere Disorders

Amany I. Gorgy, MD; Naudia L. Jonassaint, MD; Susan E. Stanley, BS; Ayman Koteish, MD; Amy E. DeZern, MD; Jolan E. Walter, MD, PhD; Sabrina C. Sopha, MD; James P. Hamilton, MD; Julie Hoover-Fong, MD, PhD; Allen R. Chen, MD; Robert A. Anders, MD, PhD; Ihab R. Kamel, MD; Mary Armanios, MD
Author and Funding Information

From the Departments of Oncology (Drs Gorgy, DeZern, Chen, and Armanios and Ms Stanley), Medicine (Drs Jonassaint, Koteish, DeZern, and Hamilton), Pathology (Drs Sopha, Anders, and Armanios), Pediatrics (Dr Hoover-Fong), and Radiology (Dr Kamel), and McKusick-Nathans Institute of Genetic Medicine (Ms Stanley and Drs Hoover-Fong and Armanios), Johns Hopkins University School of Medicine, Baltimore, MD; and the Division of Allergy and Immunology (Dr Walter), Massachusetts General Hospital for Children, Boston, MA.

CORRESPONDENCE TO: Mary Armanios, MD, 1650 Orleans St, CRB 1 Room 186, Baltimore, MD 21287; e-mail: marmani1@jhmi.edu


Drs Gorgy and Jonassaint contributed equally to this work.

FUNDING/SUPPORT: This work was supported by the National Institutes of Health [RO1 CA160433] and the Commonwealth Foundation (to Dr Armanios).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(4):1019-1026. doi:10.1378/chest.15-0825
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BACKGROUND:  Telomere syndromes have their most common manifestation in idiopathic pulmonary fibrosis and emphysema. The short telomere defect in these patients may manifest systemically as bone marrow failure and liver disease. We sought to understand the causes of dyspnea in telomerase and telomere gene mutation carriers who have no parenchymal lung disease.

METHODS:  Clinical and pathologic data were reviewed as part of a Johns Hopkins-based natural history study of short telomere syndromes including dyskeratosis congenita.

RESULTS:  Hepatopulmonary syndrome (HPS) was diagnosed in nine of 42 cases (21%). Their age at presentation was significantly younger than that of cases initially presenting with pulmonary fibrosis and emphysema (median, 25 years vs 55 years; P < .001). Cases had evidence of intra- and extrapulmonary arteriovascular malformations that caused shunt physiology. Nodular regenerative hyperplasia was the most frequent histopathologic abnormality, and it was seen in the absence of cirrhosis. Dyspnea and portal hypertension were progressive, and the median time to death or liver transplantation was 6 years (range, 4-10 years; n = 6). In cases that underwent liver transplantation, dyspnea and hypoxia improved, but pulmonary fibrosis subsequently developed.

CONCLUSIONS:  This report identifies HPS as a frequent cause of dyspnea in telomerase and telomere gene mutation carriers. While it usually precedes the development of parenchymal lung disease, HPS may also co-occur with pulmonary fibrosis and emphysema. Recognizing this genetic diagnosis is critical for management, especially in the lung and liver transplantation setting.

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