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.

The role of suboptimal mitochondrial function in vulnerability to post-traumatic stress disorder
AbstractPost-traumatic stress disorder remains the most significant psychiatric condition associated with exposure to a traumatic event, though rates of traumatic event exposure far outstrip incidence of PTSD. Mitochondrial dysfunction and suboptimal mitochondrial function have been increasingly implicated in several psychopathologies, and recent genetic studies have similarly suggested a pathogenic role of mitochondria in PTSD. Mitochondria play a central role in several physiologic processes underlying PTSD symptomatology, including abnormal fear learning, brain network activation, synaptic plasticity, steroidogenesis, a...
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

Non-osteogenic muscle hypertrophy in children with McArdle disease
ConclusionWe have identified a ‘non-osteogenic muscle hypertrophy’ in children with McArdle disease. This phenomenon warrants special attention since low osteogenesis at an early age predicts a high risk for osteoporosis later in life. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 28, 2018 Category: Internal Medicine Source Type: research

A family segregating lethal neonatal coenzyme Q 10 deficiency caused by mutations in COQ9
AbstractPrimary CoQ10 deficiency is a clinically and genetically heterogeneous, autosomal recessive disorder resulting from mutations in genes involved in the synthesis of coenzyme Q10 (CoQ10). To date, mutations in nine proteins required for the biosynthesis of CoQ10 cause CoQ10 deficiency with varying clinical presentations. In 2009 the first patient with mutations in COQ9 was reported in an infant with a neonatal-onset, primary CoQ10 deficiency with multi-system disease. Here we describe four siblings with a previously undiagnosed lethal disorder characterized by oligohydramnios and intrauterine growth restriction, vari...
Source: Journal of Inherited Metabolic Disease - March 20, 2018 Category: Internal Medicine Source Type: research

Treatment with chenodeoxycholic acid in cerebrotendinous xanthomatosis: clinical, neurophysiological, and quantitative brain structural outcomes
ConclusionCDCA may reverse the pathophysiological process in patients with CTX, especially if treatment is initiated early in the disease process. Besides tendon xanthoma, this study stresses the need to consider plasma cholestanol measurement in any patient with infantile chronic diarrhea and/or jaundice, juvenile cataract, learning disability and/or autism spectrum disorder, pyramidal signs, cerebellar syndrome or peripheral neuropathy. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 20, 2018 Category: Internal Medicine Source Type: research

Proposal for an individualized dietary strategy in patients with very long-chain acyl-CoA dehydrogenase deficiency
ConclusionsThis study shows that a strict diet cannot prevent poor clinical outcome in severely affected patients and that the LC-FAO flux is a good predictor of clinical outcome in individuals with VLCADD identified before its introduction in NBS. Hereby, we propose an individualized dietary strategy based on the LC-FAO flux score. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Unraveling the unknown areas of the human metabolome: the role of infrared ion spectroscopy
AbstractThe identification of molecular biomarkers is critical for diagnosing and treating patients and for establishing a fundamental understanding of the pathophysiology and underlying biochemistry of inborn errors of metabolism. Currently, liquid chromatography/high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy are the principle methods used for biomarker research and for structural elucidation of small molecules in patient body fluids. While both are powerful techniques, several limitations exist that often make the identification of unknown compounds challenging. Here, we describe how infrar...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Long-term follow-up of 17 patients with childhood Pompe disease treated with enzyme replacement therapy
ConclusionsWe report a positive effect of ERT in patients with childhood Pompe disease at group level. For some patients, new or personalized treatments should be considered. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Contribution of tandem mass spectrometry to the diagnosis of lysosomal storage disorders
AbstractTandem mass spectrometry (MS/MS) is a highly sensitive and specific technique. Thanks to the development of triple quadrupole analyzers, it is becoming more widely used in laboratories working in the field of inborn errors of metabolism. We review here the state of the art of this technique applied to the diagnosis of lysosomal storage disorders (LSDs) and how MS/MS has changed the diagnostic rationale in recent years. This fine technology brings more sensitive, specific, and reliable methods than the previous biochemical ones for the analysis of urinary glycosaminoglycans, oligosaccharides, and sialic acid. In sph...
Source: Journal of Inherited Metabolic Disease - March 19, 2018 Category: Internal Medicine Source Type: research

Think big — think omics
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 14, 2018 Category: Internal Medicine Source Type: research

Multiomics tools for the diagnosis and treatment of rare neurological disease
AbstractConventional workup of rare neurological disease is frequently hampered by diagnostic delay or lack of diagnosis. While biomarkers have been established for many neurometabolic disorders, improved methods are required for diagnosis of previously unidentified or underreported causes of rare neurological disease. This would result in a higher diagnostic yield and increased patient numbers required for interventional studies. Recent studies using next-generation sequencing and metabolomics have led to identification of novel disease-causing genes and biomarkers. This combined approach can assist in overcoming challeng...
Source: Journal of Inherited Metabolic Disease - March 13, 2018 Category: Internal Medicine Source Type: research

Promises and pitfalls of untargeted metabolomics
AbstractMetabolomics is one of the newer omics fields, and has enabled researchers to complement genomic and protein level analysis of disease with both semi-quantitative and quantitative metabolite levels, which are the chemical mediators that constitute a given phenotype. Over more than a decade, methodologies have advanced for both targeted (quantification of specific analytes) as well as untargeted metabolomics (biomarker discovery and global metabolite profiling). Untargeted metabolomics is especially useful when there is no a priori metabolic hypothesis. Liquid chromatography coupled to mass spectrometry (LC-MS) has ...
Source: Journal of Inherited Metabolic Disease - March 13, 2018 Category: Internal Medicine Source Type: research

Quantification of gait in children with mitochondrial disease
In conclusion, measuring spatiotemporal parameters of gait using the GAITRite in ambulatory children with mitochondrial disease is feasible and reliable for most of the parameters measured. When using gait analysis in future studies in children with mitochondrial disease, we advise i) to use an exercise test prior to the gait analysis, ii) to let children practice the test before the actual data collection, and iii) not to use symmetry parameters. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 12, 2018 Category: Internal Medicine Source Type: research

Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders
In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 9, 2018 Category: Internal Medicine Source Type: research

The impact of ammonia levels and dialysis on outcome in 202 patients with neonatal onset urea cycle disorders
In conclusion, in s evere neonatal onset hyperammonemia, the current practice of dialysis, which effectively clears ammonia, had no impact on outcome. It may be essential for improving outcome to initiate all available treatment options, including dialysis, as early as possible. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - March 8, 2018 Category: Internal Medicine Source Type: research

Tetrahydrobiopterin treatment reduces brain L-Phe but only partially improves serotonin in hyperphenylalaninemic ENU1/2 mice
AbstractHyperphenylalaninemia (HPA) caused by hepatic phenylalanine hydroxylase (PAH) deficiency has severe consequences on brain monoamine neurotransmitter metabolism. We have studied monoamine neurotransmitter status and the effect of tetrahydrobiopterin (BH4) treatment inPahenu1/enu2 (ENU1/2) mice, a model of partial PAH deficiency. These mice exhibit elevated blood L-phenylalanine (L-Phe) concentrations similar to that of mild hyperphenylalaninemia (HPA), but brain levels of L-Phe are still ~5-fold elevated compared to wild-type. We found that brain L-tyrosine, L-tryptophan, BH4 cofactor and catecholamine concentration...
Source: Journal of Inherited Metabolic Disease - March 8, 2018 Category: Internal Medicine Source Type: research