Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients

被引:47
作者
Sturla, L
Puglielli, L
Tonetti, M
Berninsone, P
Hirschberg, CB
De Flora, A
Etzioni, A
机构
[1] Univ Genoa, Dept Expt Med, Biochem Sect, I-16132 Genoa, Italy
[2] Ist Giannina Gaslini, I-16132 Genoa, Italy
[3] Boston Univ, Goldman Sch Grad Dent, Dept Mol & Cell Biol, Boston, MA 02118 USA
[4] Technion Israel Inst Technol, Rappaport Sch Med, Rambam Med Ctr, Dept Pediat & Immunol, IL-31096 Haifa, Israel
关键词
D O I
10.1203/00006450-200104000-00016
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Leukocyte adhesion deficiency type II is an autosomal recessive syndrome characterized by generalized reduction of L-fucose in glycoconjugates; the specific molecular defect is still undefined. The most important clinical symptoms include severe growth and mental retardation and severe immunodeficiency. Patients from two ethnic groups have been reported, i.e. Arab and Turkish. We have observed that GDP-L-fucose transport into Golgi vesicles was specifically impaired in an Arab patient, with a significant reduction of the V-max but no significant differences in the K-m from control and parents. GDP-L-fucose transport showed simple saturation kinetics in all samples. Transport of UDP-galactose, UDP-N-acetylglucosamine, and CMP-sialic acid was comparable into vesicles from the Arab patient, parents, and control. These kinetic parameters probably account for the failure to obtain any clinical and biochemical response to fucose therapy in Arab patients. This contrasts both with the distinctive kinetic properties of GDP-L-fucose transport and with the success of fucose therapy, which have been recently reported in one patient of Turkish origin. Accordingly, the biochemical properties of CIDP-L-fucose transport into the Golgi are consistent with different variants of leukocyte: adhesion deficiency type II that an probably the result of different molecular defects.
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页码:537 / 542
页数:6
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