Format

Send to

Choose Destination
Chest. 2015 Oct;148(4):1019-1026. doi: 10.1378/chest.15-0825.

Hepatopulmonary syndrome is a frequent cause of dyspnea in the short telomere disorders.

Author information

1
Department of Oncology, Baltimore, MD.
2
Department of Medicine, Baltimore, MD.
3
Department of Oncology, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
4
Department of Oncology, Baltimore, MD; Department of Medicine, Baltimore, MD.
5
Department of Division of Allergy and Immunology, Massachusetts General Hospital for Children, Boston, MA.
6
Department of Pathology, Baltimore, MD.
7
Department of Pediatrics, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD.
8
Department of Radiology, Baltimore, MD.
9
Department of Oncology, Baltimore, MD; Department of Pathology, Baltimore, MD; McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD. Electronic address: marmani1@jhmi.edu.

Abstract

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.

PMID:
26158642
PMCID:
PMC4594621
DOI:
10.1378/chest.15-0825
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center