{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T15:28:47Z","timestamp":1794324527168,"version":"4.9.0"},"reference-count":33,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2011,3,29]],"date-time":"2011-03-29T00:00:00Z","timestamp":1301356800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Inher Metab Disea"],"published-print":{"date-parts":[[2011,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Pulmonary arterial hypertension (PAH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of type 1 Gaucher disease (GD1). We examined <jats:italic>GBA1<\/jats:italic> genotype, spleen status, Severity Score Index (SSI), and other patient characteristics as determinants of GD\/PAH\u2010HPS phenotype. We also examined the long\u2010term outcomes of imiglucerase enzyme replacement therapy (ERT) +\/\u2212 adjuvant therapies in 14 consecutive patients. We hypothesized a role of <jats:italic>BMPR2<\/jats:italic> and <jats:italic>ALK1<\/jats:italic> as genetic modifiers underlying GD\/PAH\u2010HPS phenotype. Median age at diagnosis of GD1 was 5 yrs (2\u201322); PAH was diagnosed at median 36 yrs (22\u201363). There was a preponderance of females (ratio 5:2). ERT was commenced at median 36.5 yrs (16\u201353) and adjuvant therapy at 36 yrs (24\u201357). <jats:italic>GBA1<\/jats:italic> genotype was N370S homozygous in two patients, N370S heteroallelic in 12. Median SSI was 15 (7\u201320). All patients had undergone splenectomy at median age 12 yrs (2\u201330). In three patients, HPS was the initial presentation, and PAH developed after its resolution; in these three, HPS responded dramatically to ERT. In seven patients, sequencing of the coding regions of <jats:italic>BMPR2<\/jats:italic> and <jats:italic>ALK1<\/jats:italic> was undertaken: 3\/7 were heterozygous for <jats:italic>BMPR2<\/jats:italic> polymorphisms; none harbored <jats:italic>ALK1<\/jats:italic> variants. With ERT (\u00b1 adjuvant therapy), 5\/14 improved dramatically, five remained stable, two worsened, and two died prematurely. In this largest series of GD\/PAH\u2010HPS patients, there is preponderance of females and N370S heteroallelic <jats:italic>GBA1<\/jats:italic> genotype. Splenectomy appears essential to development of this phenotype. In some patients, HPS precedes PAH. <jats:italic>BMPR2<\/jats:italic> and <jats:italic>ALK1<\/jats:italic> appear not be modifier genes for this rare phenotype of GD. ERT +\/\u2212 adjuvant therapy improves prognosis of this devastating GD phenotype.<\/jats:p>","DOI":"10.1007\/s10545-011-9313-9","type":"journal-article","created":{"date-parts":[[2011,3,28]],"date-time":"2011-03-28T09:23:07Z","timestamp":1301304187000},"page":"643-650","source":"Crossref","is-referenced-by-count":63,"title":["Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long\u2010term outcomes of therapy"],"prefix":"10.1002","volume":"34","author":[{"given":"Sarah Michelman","family":"Lo","sequence":"first","affiliation":[{"name":"Section of Hematology\u2010Oncology, Department of Pediatrics Yale University School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Section of Gastroenterology and Hepatology Yale University School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Chen","sequence":"additional","affiliation":[{"name":"Section of Digestive Diseases, Department of Internal Medicine Yale University School of Medicine New Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. 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