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Pulmonary Hypertension Developing after Alglucerase Therapy in Two Patients with Type 1 Gaucher Disease Complicated by the Hepatopulmonary Syndrome
- Arthur Dawson, MD;
- Darlene J. Elias, MD;
- David Rubenson, MD;
- Stephen H. Bartz, MD, PhD;
- Paul R. Garver, MD;
- Andrea C. Kay, MD;
- Colin M. Bloor, MD; and
- Ernest Beutler, MD
- From Scripps Clinic and Research Foundation and the Scripps Research Institute, La Jolla, California; and the University of California at San Diego Medical Center, San Diego, California. Grant Support: By the General Clinical Research Center Grant M01-RR00833 and Department of Academic Affairs, Scripps Clinic and Research Foundation. Requests for Reprints: Arthur Dawson, MD, Division of Chest and Critical Care Medicine, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037. Current Author Addresses: Drs. Dawson and Elias: Division of Chest and Critical Care Medicine, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037. Drs. Rubenson and Bartz: Division of Cardiovascular Diseases, Scripps Clinic and Research Foundation, 10666 North Torrey Pines Road, La Jolla, CA 92037.
Gaucher disease is an autosomal-recessive disorder that is caused by a deficiency of the enzyme glucocerebrosidase and results in accumulation of an insoluble glucocerebroside in macrophages. Type 1 (chronic non-neuropathic or “adult”) Gaucher disease is usually characterized by hepatosplenomegaly, thrombocytopenia, and skeletal complications (including bone pain, osteonecrosis, and pathologic fractures) [1, 2]. With the exception of splenectomy, few options were available for treating this disorder until enzyme replacement therapy with alglucerase became available [3]. Pulmonary involvement has long been recognized as a rare complication of Gaucher disease. Pulmonary hypertension, severe hypoxemia, and infiltration of the lungs with Gaucher cells have been described in case reports and small case series.
We report the results of therapy with alglucerase in two patients with severe hypoxemia and intrapulmonary vascular dilatations that appeared on agitated saline contrast echocardiography [4].
Case Reports
Patient 1
A previous article [3] and two case series [2, 5] described patient 1. We first evaluated this patient in 1984 when she was 23 years of age. Progressive dyspnea began when the patient was about 20 years of age; by 1990, she would become breathless after walking a few steps. The patient was small (height, 159 cm; weight, 40 kg) and deeply cyanotic with clubbing of the fingers and a large liver. Bronchoalveolar lavage fluid and transbronchial lung biopsy specimens showed no Gaucher cells. Results of studies of lung function are shown in Table 1.
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Therapy with alglucerase began in January 1990. The patient initially received alglucerase, 30 U/kg of body weight per month at 3.3 U/kg twice weekly. After 7 months, the dose was reduced to 2.3 U/kg twice weekly. After 33 months, the patient no longer needed administration of oxygen and was working full-time, but chest radiography …
