Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2008-12-5
pubmed:abstractText
Gaucher disease is a lysosomal storage disorder caused by a deficiency of the enzyme acid beta-glucosidase. The most prevalent mutant genotype in type I Gaucher disease, N370S/N370S, is commonly thought to confer a mild phenotype presenting in adulthood. To characterize a subset of more severely affected N370S homozygotes, we assessed the phenotypes at or near the time of diagnosis of all N370S homozygotes with available data enrolled in the International Collaborative Gaucher Group Gaucher Registry. N370S compound heterozygotes were analyzed for comparison, as they are expected to present with a more severe phenotype. Of 798 N370S homozygotes and 1,278 N370S compound heterozygotes identified, 32% (251/788) and 65% (820/1269), respectively, were diagnosed before age 20 years. At diagnosis, N370S homozygotes as compared to N370S compound heterozygotes had the following clinical characteristics: irreversible skeletal lesions 17% (34/198) for N370S homozygotes versus 26% (76/290) for N370S compound heterozygotes; anaemia 18% (59/327) versus 29% (145/494); thrombocytopenia 52% (170/327) versus 62% (281/453); hepatomegaly 44% (83/190) versus 72% (141/195); splenomegaly 73% (142/194) versus 91% (178/195); and osteopenia or osteoporosis 48.6% (34/70) versus 51% (25/49). Some N370S homozygotes exhibited more severe clinical manifestations: 9% (29/327) had severe thrombocytopenia; 3% (5/190) had severe hepatomegaly; 11% (22/194) had severe splenomegaly; 7% (18/255) reported bone crises; 11% (8/70) had osteoporosis. In conclusion, N370S homozygosity does not consistently confer a mild, adult-onset phenotype. Gaucher disease patients with the N370S/N370S genotype exhibit a high degree of phenotypic heterogeneity and some may be at risk for early disease onset and severe clinical manifestations.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1573-2665
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
31
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
738-44
pubmed:dateRevised
2009-5-29
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Phenotypic heterogeneity of N370S homozygotes with type I Gaucher disease: an analysis of 798 patients from the ICGG Gaucher Registry.
pubmed:affiliation
UCSF, San Francisco, CA, USA.
pubmed:publicationType
Journal Article