Roles of specific cytokines in bone remodeling and hematopoiesis in Gaucher disease.

BACKGROUND: Gaucher disease type 1 and type 3 are characterized by bone disease and hematological symptoms. It is known that monocyte/macrophage lineage is activated in Gaucher disease, and accordingly certain cytokines are elevated in blood. The aim of the present study was to explore the possible relationships between cytokines and bone remodeling and hematological abnormalities in this disease. METHODS: The concentrations of seven cytokines and two related proteins were measured in patients with Gaucher disease type 1 and type 3 (n= 8; age range, 2-50 years) who had received enzyme replacement therapy. RESULTS: Concentrations of interleukin-18 and transforming growth factor-beta1 were elevated in patients of all clinical types. Elevation of these cytokines in Gaucher disease has not been previously reported. Analysis of correlation among cytokines and bone-turnover markers showed that interleukin-18 concentration was correlated with each of two bone formation markers of bone-specific alkaline phosphatase activity and osteocalcin concentration, whereas macrophage colony-stimulating factor concentration correlated with the bone absorption marker of N-telopeptide to helix in urine. Concentrations of macrophage colony-stimulating factor and tumor necrosis factor-alpha were inversely correlated with hemoglobin concentration. CONCLUSIONS: Interleukin-18 and monocyte macrophage colony-stimulating factor are cytokines mainly involved in the mechanism of bone disease, while macrophage colony-stimulating factor and tumor necrosis factor-alpha may play a role in the development of hematological abnormalities in Gaucher disease.

Late-onset ornithine transcarbamylase deficiency in male patients: prognostic factors and characteristics of plasma amino acid profile.

BACKGROUND: The occurrence of male patients with ornithine transcarbamylase (OTC) deficiency during adolescence or in adulthood has now been recognized. The aim of this study was to determine the prognostic factors that affect the prognosis of life, to explore a basis for therapeutic strategy. METHODS: In 10 patients, nine of whom carried the R40H mutation and the other one carrying the Y55D mutation in the OTC gene, 32 demographic and laboratory data were first compared between survivors and non-survivors, using the unpaired t-test. The factors with significant difference were then subjected to multiple regression analysis. RESULTS: The factors that exhibited significant difference were: age at onset, concentration of plasma ammonium, blood pH, and concentrations of six amino acids in plasma. The multiple regression analysis then revealed concentrations of ammonium, leucine, lysine, isoleucine, phenylalanine, glutamine and proline to be significant prognostic factors. The amino acid profile in the 10 patients showed increases in glutamine, proline, lysine, valine and methionine, and decreases in serine, ornithine and arginine. There was an inverse correlation between the age at onset and the level of the residual hepatic OTC activity. CONCLUSION: The results implied that: (i) the plasma amino acid profile was unique, in comparison to other liver diseases; (ii) the plasma concentration of each of the (mentioned above) six amino acids was a significant predictor of prognosis; and (iii) suppression of protein catabolism, as suggested by the higher concentrations in isoleucine and leucine in the non-survivors, prevention of glutamine-induced brain edema, correction of alkalosis, and supplementation with ornithine or arginine may improve the prognosis of life.