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Long-term evaluation of urinary copper excretion and non-caeruloplasmin associated copper in Wilson disease patients under medical treatment
ConclusionDue to their variability, urinary copper excretion rates and serum copper concentrations are less than ideal parameters by which to monitor the benefit of a copper-reducing therapy. Urinary copper excretion rates seem to be more suitable than non-caeruloplasmin associated copper concentrations for this purpose. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 20, 2018 Category: Internal Medicine Source Type: research

Newborn screening for homocystinurias: recent recommendations versus current practice
ConclusionsDue to the favourable outcome of early treated patients, NBS for homocystinurias is recommended. To improve NBS, decision limits should be revised considering the population median. Relevant markers should be combined; use of the postanalytical tools offered by the CLIR project (Collaborative Laboratory Integrated Reports, which considers, e.g. birth weight and gestational age) is recommended. tHcy and methylmalonic acid should be implemented as second-tier markers. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 15, 2018 Category: Internal Medicine Source Type: research

Postsynaptic movement disorders: clinical phenotypes, genotypes, and disease mechanisms
AbstractMovement disorders comprise a group of heterogeneous diseases with often complex clinical phenotypes. Overlapping symptoms and a lack of diagnostic biomarkers may hamper making a definitive diagnosis. Next-generation sequencing techniques have substantially contributed to unraveling genetic etiologies underlying movement disorders and thereby improved diagnoses. Defects in dopaminergic signaling in postsynaptic striatal medium spiny neurons are emerging as a pathogenic mechanism in a number of newly identified hyperkinetic movement disorders. Several of the causative genes encode components of the cAMP pathway, a c...
Source: Journal of Inherited Metabolic Disease - June 13, 2018 Category: Internal Medicine Source Type: research

Oxygen in mitochondrial disease: can there be too much of a good thing?
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 8, 2018 Category: Internal Medicine Source Type: research

The phenotype of adult versus pediatric patients with inborn errors of metabolism
AbstractUntil recently, inborn errors of metabolism (IEM) were considered a pediatric specialty, as emphasized by the term “inborn,” and the concept of adult onset IEM has only very recently reached the adult medical community. Still, an increasing number of adult onset IEM have now been recognized, as new metabolomics and molecular diagnostic techniques have become available. Here, we discuss possible mechanisms un derlying phenotypic variability in adult versus children with IEM. Specifically, phenotypic severity and age of onset are expected to be modulated by differences in residual protein activity possibly driven...
Source: Journal of Inherited Metabolic Disease - June 6, 2018 Category: Internal Medicine Source Type: research

The effectiveness of enzyme replacement therapy for juvenile-onset Pompe disease: a systematic review
ConclusionsInterpretation of the findings was hindered by the lack of good quality evidence. The available data suggests that some JOPD patients may benefit in the short term from ERT through improved muscle strength and a reduced need for assisted ventilation. A focus by clinicians on improved and more consistent evidence collection, and use of study designs tailored to rare conditions, would provide more definitive results. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 5, 2018 Category: Internal Medicine Source Type: research

Influence of implementing a protocol for an intravenously administered ammonia scavenger on the management of acute hyperammonemia in a pediatric intensive care unit
This study is the first to compare two SBSP delivery strategies in the treatment of acute hyperammonemia in this PICU setting. Implementation of a delivery protocol shortened the time from diagnosis of hyperammonemia to prescription of SBSP and h elped us identify other parameters that can be improved to optimize treatment delivery. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 5, 2018 Category: Internal Medicine Source Type: research

Polycystic kidney features of the renal pathology in glycogen storage disease type I: possible evolution to renal neoplasia
AbstractGlycogen storage disease type I (GSDI) is a rare genetic pathology characterized by glucose-6 phosphatase (G6Pase) deficiency, translating in hypoglycemia during short fasts. Besides metabolic perturbations, GSDI patients develop long-term complications, especially chronic kidney disease (CKD). In GSDI patients, CKD is characterized by an accumulation of glycogen and lipids in kidneys, leading to a gradual decline in renal function. At a molecular level, the activation of the renin-angiotensin system is responsible for the development of renal fibrosis, eventually leading to renal failure. The same CKD phenotype wa...
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Metabolism of amino acid neurotransmitters: the synaptic disorder underlying inherited metabolic diseases
AbstractAmino acids are involved in various metabolic pathways and some of them also act as neurotransmitters. Since biosynthesis ofl-glutamate and γ-aminobutyric acid (GABA) requires 2-oxoglutarate while 3-phosphoglycerate is the precursor ofl-glycine andd-serine, evolutionary selection of these amino acid neurotransmitters might have been driven by their capacity to provide important information about the glycolytic pathway and Krebs cycle. Synthesis and recycling of amino acid neurotransmitters as well as composition and function of their receptors are often compromised in inherited metabolic diseases. For instance, in...
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Risks and benefits of oxygen therapy
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Characteristics and outcomes of patients with formiminoglutamic aciduria detected through newborn screening
ConclusionsThese data suggest that the majority of individuals with FTCD deficiency detected by newborn screening are asymptomatic. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Inhibiting PNP for the therapy of hyperuricemia in Lesch-Nyhan disease: preliminary in vitro studies with analogues of immucillin-G
We report studies conducted in primary cultures of skin fibroblasts from controls and LND patients grown in the presence of the PNP inhibitor. Cell viability, oxypurine release in culture medium, and endocellular nucleotide pattern have been monitored in different growth conditions (inhibitor concentration, time, added inosine). Our results demonstrate effective PNP inhibition by low inhibitor concentration, with reduced hypoxanthine release, and no appreciable toxicity in control or patient cells, suggesting a new therapeutic strategy for LND hyperuricemia. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Lipids and synaptic functions
AbstractSynaptic functions have long been thought to be driven by proteins, especially the SNARE complex, contrasting with a relatively passive role for lipids constituting cell membranes. It is now clear that not only lipids, i.e. glycerophospholipids, sphingolipids and sterols, play a determinant role in the dynamics of synaptic membranes but they also actively contribute to the endocytosis and exocytosis of synaptic vesicles in conjunction with synaptic proteins. On the other hand, a growing number of inborn errors of metabolism affecting the nervous system have been related to defects in the synthesis and remodelling o...
Source: Journal of Inherited Metabolic Disease - June 4, 2018 Category: Internal Medicine Source Type: research

Combined malonic and methylmalonic aciduria due to ACSF3 mutations: benign clinical course in an unselected cohort
ConclusionBecause our province still performs urine newborn screening, our patient cohort is the only one free of selection bias. Therefore, the favorable clinical course observed suggests that CMAMMA is probably a benign condition, although we cannot exclude the possibility that a small minority of patients may present symptoms attributable to CMAMMA, perhaps as a result of interactions with other genetic or environmental factors. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 1, 2018 Category: Internal Medicine Source Type: research

Efficacy and safety of Velmanase alfa in the treatment of patients with alpha-mannosidosis: results from the core and extension phase analysis of a phase III multicentre, double-blind, randomised, placebo-controlled trial
ConclusionsThese findings support the utility of VA for the treatment of AM, with more evident benefit over time and when treatment is started in the paediatric age. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 30, 2018 Category: Internal Medicine Source Type: research