Homocysteine is an intermediate of methionine metabolism, and its elevation in tissues is correlated with an increased risk for vascular diseases. We measured homocysteine in plasma of 24 patients with acute intermittent porphyria (AIP) and long-term high excretion of heme precursors. Fifteen (62.5%) presented hyperhomocysteinemia (total homocysteine in plasma >15 μmol/L). No association was found between hyperhomocysteinemia and either urinary excretion of heme precursors or clinical status. All the patients showed normal levels of vitamin B₁₂ and folic acid, but 13 (54%) presented low plasma levels of pyridoxal 5'-phosphate (PLP <15 nmol/L). Cystathionine β-synthase (CBS) catalyzes a major removal pathway of homocysteine and is dependent on both PLP and heme as cofactors. It is hypothesized that, in AIP, CBS reduced hepatic activity resulting from either a low heme status and/or consumptive depletion of PLP due to increased demand by 5-aminolevulinatesynthase hyperactivity can induce hyperhomocysteinemia.
[Show abstract][Hide abstract] ABSTRACT: There is accumulating evidence for an increased prevalence of metabolic syndrome (MetS) in bipolar patients, which is comparable to the prevalence of MetS in patients with schizophrenia. Hyperhomocysteinaemia has emerged as an independent and graded risk factor for the development of cardiovascular disease (CVD), which is, at the same time, the primary clinical outcome of MetS. The aim of this study was to ascertain if the presence of MetS was associated with hyperhomocysteinaemia in patients with bipolar disorder (N=36) and schizophrenia (N=46) treated with second-generation antipsychotics (SGA). MetS was defined according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP-III) criteria and the cut-off point for hyperhomocysteinaemia was set up at 15 μmoll(-1). Results of the study indicated that the presence of the MetS is statistically significantly associated with the elevated serum homocysteine in all participants. As hyperhomocysteinaemia has emerged as an independent risk factor for psychiatric disorder and CVD, it could be useful to include fasting homocysteine serum determination in the diagnostic panels of psychiatric patients to obtain a better assessment of their metabolic risk profile.
Psychiatry Research 08/2011; 189(1):21-5. DOI:10.1016/j.psychres.2010.11.021 · 2.47 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Vuksan-Cusa B, Sagud M, Jakovljevic M, Mihaljevic Peles A, Jaksic N, Mihaljevic S, Zivkovic M, Kudlek Mikulic S, Jevtovic S. Association between C-reactive protein and homocysteine with the subcomponents of metabolic syndrome in stable patients with bipolar disorder and schizophrenia. Nord J Psychiatry 2012;Early Online:1-6. Background: Previous studies revealed high prevalence of metabolic syndrome (MetS) in patients with bipolar disorder and schizophrenia. C-Reactive protein (CRP) and homocysteine have also both emerged as independent risk factors for the development of cardiovascular disease (CVD) but are less investigated in psychiatric disorders. Aims: The aim of this study was to ascertain which specific subcomponents of MetS are associated with levels of CRP and homocysteine in patients with bipolar disorder and schizophrenia. Methods: Our sample consisted of patient group (n = 122) (60 bipolar and 62 schizophrenic patients) treated with second-generation antipsychotics (SGA) and healthy controls (n = 59). MetS was defined according to NCEP ATP-III criteria; the cut-off point for elevated CRP was set up at 5 mg/l and for hyperhomocysteinemia at 15 μmol/l. Results: In the patient group, homocysteine was correlated with waist circumference, systolic and diastolic blood pressure, triglycerides and blood glucose, while CRP was correlated with waist circumference and diastolic blood pressure. Patients with hyperhomocysteinemia had an 8.442 times higher chance to have met the criteria for MetS while elevated CRP was not a significant predictor of MetS. Conclusions: There is a complex association between CRP and homocysteine with specific subcomponents of MetS in patients with bipolar disorder and schizophrenia. Given the high risk of cardiovascular disorders in psychiatric patients, these relationships deserve further investigation. Clinically, it could be useful to include the measurement of homocysteine and CRP levels in routine psychiatric diagnostic procedures.
[Show abstract][Hide abstract] ABSTRACT: Objective:
Acute intermittent porphyria (AIP) is an autosomal dominant disease that results from a deficiency of hydroxymethylbilane synthase, the third enzyme of the heme biosynthetic pathway. AIP carriers may present acute neurovisceral attacks with hepatic overproduction of heme-precursors. In some patients, remission of the acute symptoms leads to long-term hepatic metabolic abnormalities. In this study, gas chromatography-mass spectrometry (GC/MS) was used to investigate urinary steroid metabolome of AIP patients.
Design and methods:
Steroid profiling in urine was performed in a group of AIP patients with biochemically active disease (n=22) and healthy controls (n = 20). Five asymptomatic AIP family carriers were also studied. Commonly used ratios for the evaluation of disturbances in the steroid metabolism were calculated.
We found that etiocholanolone/androsterone and tetrahydrocortisol/5α-tetrahydrocortisol (THF/5α-THF) metabolic ratios were significantly increased in the urine of AIP patients compared to controls (2.3 ± 0.3 vs 0.8 ± 0.1; p < 0.001 and 2.9 ± 0.7 vs 0.9 ± 0.1; p < 0.01). The (THF+5α-THF)/tetrahydrocortisone ratio was reduced among the AIP patients (p < 0.01). Quantification of the steroid absolute concentrations showed that these variations were due to a decrease of the 5α metabolites. Other ratios, like cortisol/cortisone and 6β-hydroxycortisol/cortisol in the free steroid fraction did not show differences between patients and controls. All ratios were normal among the family carriers.
A significant number of AIP patients present a basal decrease of steroid 5α-reductase activity in the liver. The deficiency may be related to malnutrition and hepatic energy misbalance associated with active AIP. Urinary steroid profiling by GC/MS may be a valuable tool to assess hepatic metabolome in AIP.
Karin M. A. Swart, Annelies C. Ham, Janneke P. van Wijngaarden, Anke W. Enneman, Suzanne C. van Dijk, Evelien Sohl, Elske M. Brouwer-Brolsma, Nikita L. van der Zwaluw, M. Carola Zillikens, Rosalie A. M. Dhonukshe-Rutten, Nathalie van der Velde, Johannes Brug, André G. Uitterlinden, Lisette C. P. G. M. de Groot, Paul Lips, Natasja M. van Schoor
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