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.

Correction to: Manifesting heterozygotes in McArdle disease: a myth or a reality-role of statins
Unfortunately the name of one of the authors was spelled incorrectly in the published original article. The correct name is Alejandro Santos-Lozano. The original article got updated. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - July 20, 2018 Category: Internal Medicine Source Type: research

Outcome measures for children with mitochondrial disease: consensus recommendations for future studies from a Delphi-based international workshop
AbstractAlthough there are no effective disease-modifying therapies for mitochondrial diseases, an increasing number of trials are being conducted in this rare disease group. The use of sensitive and valid endpoints is essential to test the effectiveness of potential treatments. There is no consensus on which outcome measures to use in children with mitochondrial disease. The aims of this two-day Delphi-based workshop were to (i) define the protocol for an international, multi-centre natural history study in children with mitochondrial myopathy and (ii) to select appropriate outcome measures for a validation study in child...
Source: Journal of Inherited Metabolic Disease - July 19, 2018 Category: Internal Medicine Source Type: research

Presynaptic disorders: a clinical and pathophysiological approach focused on the synaptic vesicle
AbstractThe aim of this report is to present a tentative clinical and pathophysiological approach to diseases affecting the neuronal presynaptic terminal, with a major focus on synaptic vesicles (SVs). Diseases are classified depending on which step of the neurobiology of the SV is predominantly affected: (1) biogenesis of vesicle precursors in the neuronal soma; (2) transport along the axon; (3) vesicle cycle at the presynaptic terminal (exocytosis –endocytosis cycle, with the main purpose of neurotransmitter release). Given that SVs have been defined as individual organelles, we highlight the link between the biologica...
Source: Journal of Inherited Metabolic Disease - July 18, 2018 Category: Internal Medicine Source Type: research

Synaptic metabolism: a new approach to inborn errors of neurotransmission
AbstractTo date, inborn errors of neurotransmitters have been defined based on the classic concept of inborn error of metabolism (IEM), and they include defects in synthesis, catabolism, and transport pathways. However, the omics era is bringing insights into new diseases and is leading to an extended definition of IEM including new categories and mechanisms. Neurotransmission takes place at the synapse, the most specialized tight junction in the brain. The concept of “synaptic metabolism” would point to the specific chemical composition and metabolic functions of the synapse. Based on these specialized functions, we a...
Source: Journal of Inherited Metabolic Disease - July 16, 2018 Category: Internal Medicine Source Type: research

Cellular neurometabolism: a tentative to connect cell biology and metabolism in neurology
AbstractIt has become increasingly evident that inborn errors of metabolism (IEMs) are particularly prevalent as diseases of the nervous system and that a broader, more inclusive definition of IEM is necessary. In fact, as long as biochemistry is involved, any kind of monogenic disease can become an IEM. This new, extended definition includes new categories and mechanisms, and as a general trend will go beyond a single biochemical pathway and/or organelle, and will appear as a connection of multiple crossroads in a system biology approach.From one side, a simplified and updated classification of IEM is presented that mixes...
Source: Journal of Inherited Metabolic Disease - July 16, 2018 Category: Internal Medicine Source Type: research

Transcranial electrical stimulation (tES) mechanisms and its effects on cortical excitability and connectivity
AbstractIn this review, we describe transcranial electrical stimulation (tES) techniques currently being used in neuroscientific research, including transcranial direct  current (tDCS), alternating current (tACS) and random noise (tRNS) stimulation techniques. We explain how these techniques are used and summarise the proposed mechanisms of action for each technique. We continue by describing how each method has been used to alter endogenous neuronal oscillations and connectivity between brain regions, and we conclude by highlighting the varying effects of stimulation and discussing the future direction of these stimulati...
Source: Journal of Inherited Metabolic Disease - July 13, 2018 Category: Internal Medicine Source Type: research

Results from a 78-week, single-arm, open-label Phase 2 study to evaluate UX007 in pediatric and adult patients with severe long-chain fatty acid oxidation disorders (LC-FAOD)
AbstractLong-chain fatty acid oxidation disorders (LC-FAOD) are rare disorders characterized by acute crises of energy metabolism and severe energy deficiency that may present with cardiomyopathy, hypoglycemia, and/or rhabdomyolysis, which can lead to frequent hospitalizations and early death. An open-label Phase 2 study evaluated the efficacy of UX007, an investigational odd-carbon medium-chain triglyceride, in 29 subjects with severe LC-FAOD. UX007 was administered over 78  weeks at a target dose of 25–35% total daily caloric intake (mean 27.5%). The frequency and duration of major clinical events (hospitalizations, e...
Source: Journal of Inherited Metabolic Disease - July 9, 2018 Category: Internal Medicine Source Type: research

Induced pluripotent stem cells (iPSCs) as model to study inherited defects of neurotransmission in inborn errors of metabolism
AbstractThe ability to reprogram somatic cells to induced pluripotent stem cells (iPSCs) has revolutionized the way of modeling human disease. Especially for the modeling of rare human monogenetic diseases with limited numbers of patients available worldwide and limited access to the mostly affected tissues, iPSCs have become an invaluable tool. To study rare diseases affecting neurotransmitter biosynthesis and neurotransmission, stem cell models carrying patient-specific mutations have become highly important as most of the cell types present in the human brain and the central nervous system (CNS), including motoneurons, ...
Source: Journal of Inherited Metabolic Disease - July 6, 2018 Category: Internal Medicine Source Type: research

The efficacy of intracerebroventricular idursulfase-beta enzyme replacement therapy in mucopolysaccharidosis II murine model: heparan sulfate in cerebrospinal fluid as a clinical biomarker of neuropathology
We examined the efficacy of intracerebroventricular (ICV) enzyme replacement therapy (ERT) of idursulfase-beta (IDS- β) and evaluated the usefulness of HS as a biomarker for neuropathology in MPS II mice. We first examined the efficacy of three different doses (3, 10, and 30 μg) of single ICV injections of IDS-β in MPS II mice. After the single-injection study, its long-term efficacy was elucidated with 30 μ g of IDS-β ICV injections repeated every 4 weeks for 24 weeks. The efficacy was assessed by the HS content in the cerebrospinal fluid (CSF) and the brain of the animals along with histologic examinations and b...
Source: Journal of Inherited Metabolic Disease - July 5, 2018 Category: Internal Medicine Source Type: research

Transatlantic combined and comparative data analysis of 1095 patients with urea cycle disorders —a successful strategy for clinical research of rare diseases
ConclusionsCombined analysis of databases drawn from distinct populations opens the possibility to increase sample sizes for natural history questions, while comparative analysis utilising differences in approach to treatment can evaluate therapeutic options and enhance long-term outcome studies. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - July 4, 2018 Category: Internal Medicine Source Type: research

Cerebrospinal fluid monoamines, pterins, and folate in patients with mitochondrial diseases: systematic review and hospital experience
In conclusion, dopamine deficiency clinical signs were present in some patients with mitochondrial diseases with different genetic backgrounds. High CSF HVA values, together with a severe cerebral folate deficiency, were observed in KSS patients and in other mtDNA mutation syndromes. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - July 4, 2018 Category: Internal Medicine Source Type: research

Development and characterization of an inducible mouse model for glycogen storage disease type Ib
ConclusionsTM-induced inactivation of G6PT in these mice leads to a phenotype which mimics that of human GSD1b patients. The conditional mice we have generated represent an excellent tool to study the tissue-specific role of theG6PT gene and the mechanism of long-term complications in GSD1b. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - July 2, 2018 Category: Internal Medicine Source Type: research

View from inside
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - July 2, 2018 Category: Internal Medicine Source Type: research

A new opportunity: metabolism and neuropsychiatric disorders
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 28, 2018 Category: Internal Medicine Source Type: research

Manifesting heterozygotes in McArdle disease: a myth or a reality —role of statins
AbstractMcArdle disease is an autosomal recessive condition caused by deficiency of thePYGM gene-encoded muscle isoform of glycogen phosphorylase. Some cases of “manifesting” heterozygotes or carriers (i.e., patients who show some McArdle-like symptoms or signs despite being carriers of only one mutatedPYGM allele) have been reported in the literature but there is controversy, with misdiagnosis being a possibility. The purpose of our study was to determine if there are actually “manifesting” heterozygotes of McArdle disease and, if existing, whether statin treatment can trigger such condition. Eighty-one relatives ...
Source: Journal of Inherited Metabolic Disease - June 20, 2018 Category: Internal Medicine Source Type: research