Vascular presentation of cystathionine beta-synthase deficiency in adulthood.

Several recent studies describing a solely vascular presentation of cystathionine beta-synthase (CBS) deficiency in adulthood prompted us to analyze the frequency of patients manifesting with vascular complications in the Czech Republic. Between 1980 and 2009, a total of 20 Czech patients with CBS deficiency have been diagnosed yielding an incidence of 1:311,000. These patients were divided into three groups based on symptoms leading to diagnosis: those with vascular complications, with connective tissue manifestation and with neurological presentation. A vascular event such as a clinical feature leading to diagnosis of homocystinuria was present in five patients, while two of them had no other symptoms typical for CBS deficiency at the time of diagnosis. All patients with the vascular manifestation were diagnosed only during the past decade. The median age of diagnosis was 29 years in the vascular, 11.5 years in the connective tissue and 4.5 years in the neurological group. The ratio of pyridoxine responsive to nonresponsive patients was higher in the vascular (4 of 5 patients) and connective tissue groups (6 of 7 patients) than in the neurological group (2 of 8 patients). Mutation c.833T>C (p.I278T) was frequent in patients with vascular (6/10 alleles) and connective tissue presentation (8/14 alleles), while it was not present in patients with neurological involvement (0/16 alleles). During the last decade, we have observed patients with homocystinuria diagnosed solely due to vascular events; this milder form of homocystinuria usually manifests at greater ages, has a high ratio of pyridoxine responsiveness/nonresponsiveness, and the mutation c.833T>C (p.I278T) is often present.

Significance of lipopolysaccharide-binding protein (an acute phase protein) in monitoring critically ill patients.

INTRODUCTION: The present study was conducted to assess the value of serum concentration of lipopolysaccharide-binding protein (LBP) in patients with systemic inflammatory response syndrome (SIRS), sepsis and septic shock with respect to its ability to differentiate between infectious and noninfectious etiologies in SIRS and to predict prognosis. METHODS: This prospective cohort study was conducted in a multidisciplinary intensive care unit. Sixty-eight patients, admitted consecutively to the intensive care unit and who met criteria for SIRS, sepsis or septic shock were included. Serum LBP was measured using an immunochemiluminiscence assay. RESULTS: Serum levels of LBP were significantly increased in patients with SIRS (n = 40; median 30.6 microg/ml, range 9.2-79.5 microg/ml), sepsis (n = 19; median 37.1 microg/ml, range 11.8-76.2 microg/ml) and septic shock (n = 9; median 59.7 microg/ml, range 31.1-105 microg/ml), as compared with levels in the healthy volunteers (5.1 +/- 2.2 microg/ml; P < 0.0001). Serum LBP at study entry was statistically significantly lower in patients with SIRS than in those with septic shock (P < 0.014); no statistically significant difference existed between patients with SIRS and those with sepsis (P = 0.61). Specificity and sensitivity of an LBP concentration of 29.8 microg/ml to distinguish between infectious and noninfectious etiologies for SIRS were 50% and 74.2%, respectively. There was no statistically significant difference in LBP concentration between survivors and nonsurvivors in both groups of patients. Furthermore, in septic patients the LBP response appeared to exhibit a decreased magnitude. CONCLUSION: LBP is a nonspecific marker of the acute phase response and cannot be used as a diagnostic tool for differentiating between infectious and noninfectious etiologies of SIRS.

Genetic variants of homocysteine metabolizing enzymes and the risk of coronary artery disease.

It is unresolved whether elevated homocysteine in coronary artery disease (CAD) is the cause of arteriosclerosis or its consequence. In contrast, genetic variants of enzymes that metabolize homocysteine cannot be altered by arteriosclerosis. Consequently, their association with CAD would permit to imply causality. We modeled by regression analysis the effect of 11 variants in the methionine cycle upon CAD manifestation in 591 controls and 278 CAD patients. Among the examined variants only the carriership for the c.844ins68 in the cystathionine beta-synthase (CBS) gene was associated with a significantly lowered risk of CAD (OR=0.56; 95% CI=0.35-0.90 in the univariable, and OR=0.41, 95% CI=0.19-0.89 for obese people in the multivariable analysis, respectively). Healthy carriers of the c.844ins68 variant exhibited, compared to the wild type controls, significantly higher postload ratios of blood S-adenosylmethionine to S-adenosylhomocysteine (61.4 vs. 54.9, p=0.001) and of plasma total cysteine to homocysteine (8.6 vs. 7.3, p=0.004). The changes in these metabolites are compatible with an improved methylation status and with enhanced activity of homocysteine transsulfuration. In conclusion, the coincidence of clinical and biochemical effects of a common c.844ins68 CBS variant supports the hypothesis that compounds relating to homocysteine metabolism may play role in the development and/or progression of CAD.

Essential hypertension in adolescents: association with insulin resistance and with metabolism of homocysteine and vitamins.

BACKGROUND: Although insulin resistance and elevated plasma homocysteine are associated with hypertension in adults, the role of these conditions in the initial phase of hypertension is largely unknown. We examined whether insulin resistance and disturbed homocysteine metabolism are present in young adults at the early stages of essential hypertension. METHODS: We measured physical characteristics, plasma levels of insulin, lipids, total homocysteine, and vitamins in 164 patients with essential juvenile hypertension (median age, 19 years; 92% males) and in 173 controls (median age, 18 years; 66% males). Furthermore, we analyzed the prevalence of six polymorphisms in four genes of the methionine cycle. RESULTS: Patients with hypertension and controls differed significantly (P <.05) in body mass index, levels of insulin, high-density lipoprotein-cholesterol, fasting and post-load plasma homocysteine, and folates. Systolic blood pressure was correlated with homocysteine levels and inversely correlated with plasma folates. Logistic regression showed that fasting homocysteine, vitamin B(12), and low-density lipoprotein-cholesterol were associated with a significantly increased risk of juvenile hypertension. In contrast, the birth length, polymorphism c.2756 A-->G in the MTR gene and plasma folate were associated with a significantly decreased risk of juvenile hypertension. CONCLUSIONS: Our study showed that essential hypertension in adolescents is associated with lower folate and higher homocysteine levels, and with signs of insulin resistance. These data suggest that hypertension in young individuals may be a part of early manifestation of insulin resistance syndrome, and that disturbed folate and homocysteine metabolism may play a role in the early stages of hypertension.