Pulmonary vascular disease in Gaucher disease: clinical spectrum, determinants of phenotype and long‐term outcomes of therapy
| Autor: | F. Chen, Sarah Michelman Lo, Michael Boxer, Pramod K. Mistry, G. M. Pastores, Jun Liu, James A. Knowles, Kirk Aleck |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Lung Diseases Male medicine.medical_specialty Time Factors Adolescent Imiglucerase medicine.medical_treatment Splenectomy Gastroenterology Article Young Adult Internal medicine Genotype Genetics medicine Adjuvant therapy Humans Child Hepatopulmonary syndrome Genetics (clinical) Peripheral Vascular Diseases Gaucher Disease Vascular disease business.industry Respiratory disease Enzyme replacement therapy Middle Aged medicine.disease Surgery Phenotype Treatment Outcome Child Preschool Female business Follow-Up Studies medicine.drug |
| Zdroj: | Journal of Inherited Metabolic Disease. 34:643-650 |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1007/s10545-011-9313-9 |
| Popis: | Pulmonary arterial hypertension (PAH) and hepatopulmonary syndrome (HPS) are rare pulmonary vascular complications of type 1 Gaucher disease (GD1). We examined GBA1 genotype, spleen status, Severity Score Index (SSI), and other patient characteristics as determinants of GD/PAH-HPS phenotype. We also examined the long-term outcomes of imiglucerase enzyme replacement therapy (ERT) +/− adjuvant therapies in 14 consecutive patients. We hypothesized a role of BMPR2 and ALK1 as genetic modifiers underlying GD/PAH-HPS phenotype. Median age at diagnosis of GD1 was 5 yrs (2–22); PAH was diagnosed at median 36 yrs (22–63). There was a preponderance of females (ratio 5:2). ERT was commenced at median 36.5 yrs (16–53) and adjuvant therapy at 36 yrs (24–57). GBA1 genotype was N370S homozygous in two patients, N370S heteroallelic in 12. Median SSI was 15 (7–20). All patients had undergone splenectomy at median age 12 yrs (2–30). 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 BMPR2 and ALK1 was undertaken: 3/7 were heterozygous for BMPR2 polymorphisms; none harbored ALK1 variants. With ERT (± adjuvant therapy), 5/14 improved dramatically, five remained stable, two worsened, and two died prematurely. In this largest series of GD/PAH-HPS patients, there is preponderance of females and N370S heteroallelic GBA1 genotype. Splenectomy appears essential to development of this phenotype. In some patients, HPS precedes PAH. BMPR2 and ALK1 appear not be modifier genes for this rare phenotype of GD. ERT +/− adjuvant therapy improves prognosis of this devastating GD phenotype. |
| Databáze: | OpenAIRE |
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