Glycated albumin but not HbA1c reflects glycaemic control in patients with neonatal diabetes mellitus.

AIMS/HYPOTHESIS: It is difficult to use HbA(1c) as an indicator of glycaemic control in patients with neonatal diabetes mellitus (NDM) because of high levels of fetal haemoglobin (HbF) remaining in the blood. In this study, glycated albumin (GA), which is not affected by HbF, and HbA(1c) were compared to evaluate whether they reflect glycaemic control in patients with NDM. METHODS: This study included five patients with NDM. Age at diagnosis was 38 ± 20 days. Insulin therapy was started in all patients, and levels of GA, HbA(1c) and HbF were measured monthly for 6 months. One-month average preprandial plasma glucose (aPPG) was calculated using self-monitoring of blood glucose. RESULTS: Plasma glucose and GA were elevated (29.7 ± 13.1 mmol/l [n = 5] and 33.3 ± 6.9% [n = 3], respectively) but HbA(1c) was within normal limits (5.4 ± 2.6% [35.5 ± 4.9 mmol/mol]; n = 4) at diagnosis. With diabetes treatment, aPPG (r = -0.565, p = 0.002), GA (r = -0.552, p = 0.003) and HbF (r = -0.855, p < 0.0001) decreased with age, whereas HbA(1c) increased (r = 0.449, p = 0.004). GA was strongly positively correlated with aPPG (r = 0.784, p < 0.0001), while HbA(1c) showed no correlation with aPPG (r = 0.221, p = 0.257) and was significantly inversely correlated with HbF (r = -0.539, p = 0.004). CONCLUSIONS/INTERPRETATION: GA is a useful indicator of glycaemic control in patients with NDM, whereas HbA(1c) is influenced by age-related changes in HbF and does not accurately reflect glycaemic control.

The role of different X-inactivation pattern on the variable clinical phenotype with Rett syndrome.

A gene for Methyl-CpG binding protein 2 (MECP2), which locates Xq28, was recently found to be responsible for Rett syndrome. Although mutational analyses of MECP2 in Rett syndrome have been extensively analyzed, the mechanism(s) by which variable clinical phenotype occurred between affected monozygotic twins or sisters have not been clarified. We hypothesized that the difference of X-inactivation pattern might explain this phenomenon. With the method based on methylation-specific PCR, we analyzed polymorphic trinucleotide repeat in the human andorogen receptor gene mapped on Xq11.2-12, using DNA samples derived from previously described monozygotic twins and sisters together with their parents. Their clinical phenotypes were reported to be significantly different between siblings. We found that (1) maternally derived allele is predominantly active than paternally derived one in three out of four patients analyzed, (2) remaining one twin patient, whose ratio of active paternal allele is almost the same level as maternal allele, showed far much severe phenotype when compared with her counterpart. Together with the finding that most of the alleles with de novo mutation are from paternal X chromosome in sporadic cases, the existence of a mechanism that suppresses mutated paternal allele activation, resulting skewed X-inactivation to make clinical phenotype milder, might be speculated. Thus, when this mechanism fails to work sufficiently by an unknown reason, severer clinical phenotype could occur.

[Clinical evaluation of a serum immunosuppressive (IS) substance in various diseases].

The IS substance (molecular weight: 52,000, pI: 2.7-3.3) levels in the serum was examined in patients with various diseases. The IS substance levels in patients with gastric, colorectal, biliary-pancreas and esophageal cancer were significantly higher than those in healthy volunteers. The level of IS substance increased in accordance with advance of cancer, showing the highest level in advanced and recurrent cancer patients. In benign disease patients, high levels of IS substance were also observed in the serum of infectious diseases and chronic renal failure. In contrast, patients with liver cirrhosis had a definite low level of IS substance. When the IS substance level was compared with other parameters in cancer patients, a definite correlation was found with immunosuppressive acidic protein and alpha 2 globulin. However, there was no correlation with skin reaction, lymphocyte number, T-cell number, or PHA induced lymphocyte blastgenesis. It is suggested that the IS substance level is a useful indicator to judge the extent of disease before operation and to estimate the clinical course after operation.

Hepatitis B e antigen-mediated membranous glomerulonephritis. Correlation of ultrastructural changes with HBeAg in the serum and glomeruli.

Immunopathologic findings in the glomeruli of six children with membranous glomerulonephritis who were carriers of hepatitis B virus were compared with serum markers of hepatitis B virus infection. Four of the patients were positive for hepatitis B e antigen (HBeAg) in the serum, were grossly proteinuric, and had abnormal liver function tests. Deposition of HBeAg, together with immunoglobulins and beta 1C, was found in the glomeruli of these patients. On electron microscopy, numerous electron-dense deposits were identified on and within the glomerular basement membrane. The remaining two patients were seropositive for antibody against HBeAg (anti-HBe); although they had previously suffered from active membranous glomerulonephritis with massive proteinuria, they were no longer proteinuric at the time of the last renal biopsy. Deposition of HBeAg was not detected in their glomeruli. Electron microscopic observation disclosed numerous electron-lucent areas which had replaced electron-dense deposits, indicating regression of the disease processes. These results delineate the etiologic role of HBeAg in maintaining active membranous changes and suggest that patients with HBeAg-mediated membranous glomerulonephritis may remit as they seroconvert from HBeAg to anti-HBe.