Differences between acylcarnitine profiles in plasma and bloodspots.

Unlabelled: Quantification of acylcarnitines is used for screening and diagnosis of inborn error of metabolism (IEM). While newborn screening is performed in dried blood spots (DBSs), general metabolic investigation is often performed in plasma. Information on the correlation between plasma and DBS acylcarnitine profiles is scarce.

The Proline/Citrulline Ratio as a Biomarker for OAT Deficiency in Early Infancy.

Deficiency of ornithine-δ-aminotransferase (OAT) in humans results in gyrate atrophy. Early diagnosis may allow initiation of treatment before irreversible damage has occurred. However, diagnosis is commonly delayed well into adulthood because of the nonspecific character of initial symptoms.

High incidence of symptomatic hyperammonemia in children with acute lymphoblastic leukemia receiving pegylated asparaginase.

Asparaginase is a mainstay of treatment of childhood acute lymphoblastic leukemia. Pegylation of asparaginase extends its biological half-life and has been introduced in the newest treatment protocols aiming to further increase treatment success. Hyperammonemia is a recognized side effect of asparaginase treatment, but little is known about its incidence and clinical relevance.

Necrotizing enterocolitis and respiratory distress syndrome as first clinical presentation of mitochondrial trifunctional protein deficiency.

Background: Newborn screening (NBS) for long-chain 3-hydroxy acyl-CoA dehydrogenase (LCHAD) deficiency does not discriminate between isolated LCHAD deficiency, isolated long-chain keto acyl-CoA (LCKAT) deficiency and general mitochondrial trifunctional protein (MTP) deficiency. Therefore, screening for LCHAD deficiency inevitably comprises screening for MTP deficiency, which is much less amenable to treatment. Furthermore, absence of a clear classification system for these disorders is still lacking.

Fatal outcome due to deficiency of subunit 6 of the conserved oligomeric Golgi complex leading to a new type of congenital disorders of glycosylation.

Deficiency of subunit 6 of the conserved oligomeric Golgi (COG6) complex causes a new combined N- and O-glycosylation deficiency of the congenital disorders of glycosylation, designated as CDG-IIL (COG6-CDG). The index patient presented with a severe neurologic disease characterized by vitamin K deficiency, vomiting, intractable focal seizures, intracranial bleedings and fatal outcome in early infancy. Analysis of oligosaccharides from serum transferrin by HPLC and mass spectrometry revealed the loss of galactose and sialic acid residues, whereas import and transfer of these sugar residues into Golgi-enriched vesicles or onto proteins, respectively, were normal to slightly reduced.

Liquid chromatography-tandem mass spectrometry assay for the quantification of free and total sialic acid in human cerebrospinal fluid.

Background: Analysis of sialic acid (SA) metabolites in cerebrospinal fluid (CSF) is important for clinical diagnosis. In the present study, a high-performance liquid chromatography-tandem mass spectrometry (HPLC/MS/MS) method for free sialic acid (FSA) and total sialic acid (TSA) in human CSF was validated.

Methods: The method utilized a simple sample-preparation procedure of protein precipitation for FSA and acid hydrolysis for TSA.

A 2D-DIGE approach to identify proteins involved in inside-out control of integrins.

Leukocyte integrins are functionally regulated by "inside-out" signaling, meaning that stimulus-induced signaling pathways act on the intracellular integrin tail and induce activation of the receptor at the outside. Both a change in conformation (affinity) and in clustering (avidity/valency) of the receptors has been described to occur. This inside-out signaling is essential for adequate migration of leukocytes to inflammatory sites; however, the exact underlying mechanism is not known.

A broad-based metabolic approach to study VLDL apoB100 metabolism in patients with ESRD and patients treated with peritoneal dialysis.

Background: Dyslipidemia is often observed in patients with end-stage renal disease (ESRD) and is associated with cardiovascular diseases. Peritoneal dialysis treatment may further deteriorate the lipoprotein abnormalities, suggesting that peritoneal dialysis alters lipid metabolism.

Methods: To study the mechanisms involved in these abnormalities in peritoneal dialysis, we measured insulin sensitivity, free fatty acids release, de novo lipogenesis (DNL), very low-density lipoprotein (VLDL) apoB100 kinetics and cholesterol synthesis in vivo in ESRD (N= 6), peritoneal dialysis patients (N= 5), and controls (N= 7) using stable isotopes.

Increased albumin and fibrinogen synthesis rate in patients with chronic renal failure.

Background: Hypoalbuminemia and hyperfibrinogenemia are frequently observed in patients with chronic renal failure (CRF) and are both associated with cardiovascular diseases. The mechanisms responsible for hypoalbuminemia and hyperfibrinogenemia in CRF are unknown.

Methods: In the present study, both albumin and fibrinogen kinetics were measured in vivo in predialysis patients (N = 6), patients on peritoneal dialysis (N = 7) and control subjects (N = 8) using l-[1-13C]-valine.

Endogenous cholesterol synthesis is associated with VLDL-2 apoB-100 production in healthy humans.

Subjects with high plasma cholesterol levels exhibit a high production of VLDL apolipoprotein B-100 (apoB-100), suggesting that cholesterol is a mediator for VLDL production. The objective of the study was to examine whether endogenous cholesterol synthesis, reflected by the lathosterol-cholesterol ratio (L-C ratio), affects the secretory rates of different VLDL subfractions. Ten healthy subjects were studied after overnight fasting.

Hypertriglyceridemia in patients with chronic renal failure: possible mechanisms.

Cardiovascular disease (CVD) is a major cause of mortality in patients with chronic renal failure (CRF) caused by numerous factors defined as traditional and uremia-related risk factors. One of these risk factors, dyslipidemia, is often observed in patients with CRF, resulting in abnormal concentrations and composition of plasma lipoproteins. The prominent features of uremic dyslipidemia are an increase in plasma triglycerides and cholesterol in nearly all lipoproteins, and a reduction in high-density lipoprotein (HDL) cholesterol.

Transferrin synthesis is increased in nephrotic patients insufficiently to replace urinary losses.

The urinary loss of transferrin is sufficient to reduce plasma transferrin concentrations in the nephrotic syndrome. Hypotransferrinemia may lead to iron loss and microcytic anemia. The mechanism responsible for the hypotransferrinemia in the nephrotic syndrome is, however, unknown.