title: The 1226G (N370S) Gaucher mutation among patients with Legg-Calve-Perthes disease.
abstract: Legg-Calve-Perthes disease (LCPD) is an avascular necrosis of the femoral head with an annual incidence of 5-15/100,000. The estimated incidence of Gaucher disease, a lysosomal recessive storage disease, is 1:850, with a carrier rate of 1:17.5 for the 1226G (N370S) mutation among Ashkenazi Jews in whom there is a predilection. Since clinical and radiological findings of avascular hip necrosis due to either Gaucher disease or LCPD may be indistinguishable, misdiagnosis may occur. The purpose of this study was to evaluate the incidence of 1226G Gaucher mutation in a cohort of radiologically confirmed LCPD patients (diagnosed 1986-2000) in Israel. Enzyme assay was performed for confirmation of affected versus carrier status in patients with the 1226G mutation. In all, 78 LCPD patients, 86% males, 51% with severe bone disease, were studied. Family history was negative for Gaucher disease. Ethnic origin was 39% Ashkenazi Jewish, 6% Arab, and 55% other ethnicities. One Ashkenazi Jewish LCPD patient was homozygous for the 1226G mutation, and 4 LCPD patients were carriers: 3 Ashkenazi Jewish and 1 Arab patient. The frequency of the 1226G mutation among the LCPD patients was increased relative to historical Ashkenazi Jewish Israeli controls (P = 0.01). Since Gaucher disease may be misdiagnosed as LCPD, glucocerebrosidase enzyme testing is recommended among Ashkenazi Jewish children diagnosed with LCPD.
authors.affiliation: National Hemophilia Center and Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel-Hashomer, Israel.
authors.forename: G
authors.initials: G
authors.lastname: Kenet
authors.forename: S
authors.initials: S
authors.lastname: Hayek
authors.forename: M
authors.initials: M
authors.lastname: Mor
authors.forename: A
authors.initials: A
authors.lastname: Lubetsky
authors.forename: L
authors.initials: L
authors.lastname: Miller
authors.forename: N
authors.initials: N
authors.lastname: Rosenberg
authors.forename: R
authors.initials: R
authors.lastname: Mosheiff
authors.forename: M
authors.initials: M
authors.lastname: Itzchaki
authors.forename: D
authors.initials: D
authors.lastname: Elstein
authors.forename: S
authors.initials: S
authors.lastname: Wientroub
authors.forename: A
authors.initials: A
authors.lastname: Zimran
mesh_terms: D004796:Clinical Enzyme Tests; D003937:Diagnosis, Differential; D005006:Ethnicity / Q000235:genetics; D005260:Female; D005776:Gaucher Disease / Q000175:diagnosis / Q000235:genetics; D005787:Gene Frequency; D005962:Glucosylceramidase / Q000032:analysis / Q000235:genetics*; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D007557:Israel / Q000208:ethnology; D007873:Legg-Calve-Perthes Disease / Q000175:diagnosis* / Q000208:ethnology / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D012189:Retrospective Studies
chemical_list: D005962:Glucosylceramidase