The clinical diagnosis of GD currently relies on demonstration of a deficient lysosomal enzyme acid [sz]-glucosidase (glucocerebrosidase [GBA]) which is responsible for the hydrolysis of glucocerebroside (glucosylceramide) into glucose and ceramide.[sup], GBA gene is the only gene in which mutations are known to cause the GD.
This led to the accumulation of glucocerebroside in the phagocyte system, which led to the formation of Gaucher cells, induced other manifestations of GD, and eventually led to GD.
An alternative form of therapy is substrate reduction; medication with miglustat (Zavesca) reduces the amount of glucocerebroside
, allowing the patient's depleted residual glucocerebrosidase activity to cope with the reduced amount of substrate.
(1) It is an autosomal recessive disorder resulting in an accumulation of glucocerebroside
within cells of the reticuloendothelial system (spleen, liver, and bone marrow) as well as the lymph nodes, tonsils, and thymus.
Because individuals with Gaucher disease cannot break down glucocerebroside
, it remains stored in some cells of the body.
Effect of various glycolipids on cAMP-kinase activity Effector Kinase activity (pmol/min) None 2.5 [+ or -] 0.2 SGL-II 63.0 [+ or -] 2.0 HF-SGL-II 59.0 [+ or -] 2.6 SGL-I 62.3 [+ or -] 1.0 SGL-I' 55.7 [+ or -] 3.0 FGL-V 49.1 [+ or -] 1.1 F-21 43.7 [+ or -] 1.8 Glucocerebroside
2.6 [+ or -] 0.1 cAMP 111.6 [+ or -] 3.7
Clinical trials for Niemann-Pick B [acid sphingomyelinase deficiency (ASM)] have recently been initiated, along with trials of alternate recombinant forms of glucocerebroside
(for Gaucher disease).
Prevalence of glucocerebroside
mutations in the Israeli Ashkenazi Jewish population.
(1973) Enzymatic synthesis of glucocerebroside
by a glucosyltransferase from embryonic chicken brain.
Replacement therapy for inherited enzyme deficiency-macrophage-targeted glucocerebroside
for Gaucher's disease.
We synthesized a series of fluorescent glucocerebrosides
that contained pyrene-labeled fatty acids containing 3-11 methylene units.
Gaucher disease is an autosomal recessive lysosomal disorder secondary to lack of the enzyme glucocerebrosidase, leading to the accumulation of glucocerebrosides
in the cells of the reticuloendothelial system, causing hepatosplenomegaly.