Journal of Inherited Metabolic Disease This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.

Understanding childhood diabetes mellitus: new pathophysiological aspects
AbstractDiabetes mellitus (DM) is not a single disease, but several pathophysiological conditions where synthesis, release, and/or action of insulin are disturbed. A progressive autoimmune/autoinflammatory destruction of islet cells is still considered the main pathophysiological event in the development of T1DM, but there is evidence that T1DM itself is a heterogeneous disease. More than 50 gene regions are closely associated with T1DM and a variety of epigenetic factors and metabolic patterns have been characterized, which may play a role in the development of T1DM. The pathogenesis and genetics of type 2 DM (T2DM) are d...
Source: Journal of Inherited Metabolic Disease - December 15, 2017 Category: Internal Medicine Source Type: research

An overview of combined D-2- and L-2-hydroxyglutaric aciduria: functional analysis of CIC variants
AbstractCombined D-2- and L-2-hydroxyglutaric aciduria (D/L-2-HGA) is a devastating neurometabolic disorder, usually lethal in the first years of life. Autosomal recessive mutations in theSLC25A1 gene, which encodes the mitochondrial citrate carrier (CIC), were previously detected in patients affected with combined D/L-2-HGA. We showed that transfection of deficient fibroblasts with wild-typeSLC25A1 restored citrate efflux and decreased intracellular 2-hydroxyglutarate levels, confirming that deficient CIC is the cause of D/L-2-HGA. We developed and implemented a functional assay and applied it to all 17 missense variants ...
Source: Journal of Inherited Metabolic Disease - December 13, 2017 Category: Internal Medicine Source Type: research

Correction to: Impact of age at onset and newborn screening on outcome in organic acidurias
AbstractDue to an unfortunate error during the typesetting process, the collaborators were presented incorrectly. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - December 12, 2017 Category: Internal Medicine Source Type: research

AMP-activated protein kinase activation in mediating phenylalanine-induced neurotoxicity in experimental models of phenylketonuria
AbstractPhenylketonuria (PKU), one of the most prevalent autosomal recessive disorders of amino acid metabolism, is characterized by abnormal accumulation of phenylalanine, which can lead to intellectual disability. The main pathologic changes in the central nervous system of untreated phenylketonuric patients are reductions in the number of axons, dendrites, and synapses in the brain. Such alterations are thought to be mainly associated with the toxic effects caused by phenylalanine. However, the underlying molecular mechanisms have not been fully elucidated. The present study shows that a high concentration of phenylalan...
Source: Journal of Inherited Metabolic Disease - December 11, 2017 Category: Internal Medicine Source Type: research

Do inborn errors of metabolism confer or impede the risk of diabetes?
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - December 11, 2017 Category: Internal Medicine Source Type: research

Plasma lipidomics as a diagnostic tool for peroxisomal disorders
In this study, we demonstrate the potential of lipidomics for the diagnosis of peroxisomal disorders using plasma samples from patients with different types of peroxisomal disorders. We show that the changes in the plasma profiles of phospholipids, di- and triglycerides, and cholesterol esters correspond with the characteristic metabolite abnormalities that are currently used in the metabolic screening for peroxisomal disorders. The lipidomics approach, however, gives a much more detailed overview of the metabolic changes that occur in the lipidome. Furthermore, we identified novel unique lipid species for specific peroxis...
Source: Journal of Inherited Metabolic Disease - December 5, 2017 Category: Internal Medicine Source Type: research

Daily variation of NTBC and its relation to succinylacetone in tyrosinemia type 1 patients comparing a single dose to two doses a day
DiscussionNTBC could be less stable than previously considered, thus dosing NTBC once daily and lower concentrations may be less adequate. Further research including more data is necessary to establish the optimal dosing of NTBC. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 23, 2017 Category: Internal Medicine Source Type: research

Neural cells generated from human induced pluripotent stem cells as a model of CNS involvement in mucopolysaccharidosis type II
AbstractMucopolysaccharidosis type II (MPSII) is a rare X-linked lysosomal storage disorder caused by mutations in the iduronate-2-sulfatase (IDS) gene (IDS, Xq28). MPSII is characterized by skeletal deformities, hearing loss, airway obstruction, hepatosplenomegaly, cardiac valvular disease, and progressive neurological impairment. At the cellular level, IDS deficiency leads to lysosomal storage of glycosaminoglycans (GAGs), dominated by accumulation of dermatan and heparan sulfates. Human induced pluripotent stem cells (iPSC) represent an alternative system that complements the available MPSII murine model. Herein we repo...
Source: Journal of Inherited Metabolic Disease - November 22, 2017 Category: Internal Medicine Source Type: research

Propionyl-CoA carboxylase pcca-1 and pccb-1 gene deletions in Caenorhabditis elegans globally impair mitochondrial energy metabolism
AbstractPropionic acidemia (PA) is a classical inborn error of metabolism with high morbidity that results from the inability of the propionyl-CoA carboxylase (PCC) enzyme to convert propionyl-CoA to methylmalonyl-CoA. PA is inherited in an autosomal recessive fashion due to functional loss of both alleles of eitherPCCA orPCCB. These genes are highly conserved across evolutionarily diverse species and share extensive similarity withpcca-1 andpccb-1 in the nematode,Caenorhabditis elegans. Here, we report the global metabolic effects of deletion in a single PCC gene, eitherpcca-1 orpccb-1, inC. elegans. Animal lifespan was s...
Source: Journal of Inherited Metabolic Disease - November 20, 2017 Category: Internal Medicine Source Type: research

Newborn screening for lysosomal storage disorders by tandem mass spectrometry in North East Italy
ConclusionsSimultaneously determining multiple enzyme activities by MS/MS, with a focus on specific biochemical markers, successfully detected newborns with LSDs. The high incidence of these disorders supports this screening program. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 15, 2017 Category: Internal Medicine Source Type: research

Structural elucidation of novel biomarkers of known metabolic disorders based on multistage fragmentation mass spectra
AbstractSpecific diagnostic markers are the key to effective diagnosis and treatment of inborn errors of metabolism (IEM). Untargeted metabolomics allows for the identification of potential novel diagnostic biomarkers. Current separation techniques coupled to high-resolution mass spectrometry provide a powerful tool for structural elucidation of unknown compounds in complex biological matrices. This is a proof-of-concept study testing this methodology to determine the molecular structure of as yet uncharacterizedm/z signals that were significantly increased in plasma samples from patients with phenylketonuria and 3-hydroxy...
Source: Journal of Inherited Metabolic Disease - November 14, 2017 Category: Internal Medicine Source Type: research

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K
ConclusionBleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 14, 2017 Category: Internal Medicine Source Type: research

Correlation between the molecular effects of mutations at the dimer interface of alanine –glyoxylate aminotransferase leading to primary hyperoxaluria type I and the cellular response to vitamin B 6
We examined the effects of pathogenic interfacial mutations by combining bioinformatic predictions with molecular and cellular studies on selected variants (R36H, G42E, I56N, G63R, and G216R), in both their holo- (i.e., with bound PLP) and apo- (i.e., without bound PLP) form. We found that all variants displayed structural alterations mainly related to the apoform and consisting of an altered tertiary and quaternary structure. G216R also shows a strongly reduced catalytic efficiency. Moreover, all but G216R respond to vitamin B6, as shown by their increased specific activity and expression level in a cellular disease model...
Source: Journal of Inherited Metabolic Disease - November 6, 2017 Category: Internal Medicine Source Type: research

Role of protein carbonylation in diabetes
AbstractDiabetes mellitus is a metabolic disease characterized by, among others, elevated blood glucose levels. Hyperglycaemia as well as enhanced levels of glucose-derived reactive metabolites contribute to the development of diabetic complications partly via increased generation of reactive oxygen species (ROS). ROS are not only part of signaling pathways themselves but also lead to carbonylation of particular amino acid side chains by direct metal-catalyzed oxidation. In addition, carbonyl groups can be introduced into proteins indirectly by non-oxidative covalent adduction of reactive carbonyl species generated by the ...
Source: Journal of Inherited Metabolic Disease - November 6, 2017 Category: Internal Medicine Source Type: research

Priapism in a Fabry disease mouse model is associated with upregulated penile nNOS and eNOS expression
In conclusion, thes e data suggested that increased nNOS (and probably eNOS) content and the consequential elevated NO production and high arterial blood flow in the penis may be the underlying mechanism of priapism in Fabry mice. Furthermore, in combination with previous findings, this study suggested that regulation of NOS expression is susceptible to α-galactosidase A deficiency, and this may represent a general pathogenic mechanism of Fabry vasculopathy. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 6, 2017 Category: Internal Medicine Source Type: research