Journal of Inherited Metabolic Disease 

About: Journal of Inherited Metabolic Disease is an academic journal published by Springer Science+Business Media. The journal publishes majorly in the area(s): Population & Enzyme replacement therapy. It has an ISSN identifier of 0141-8955. Over the lifetime, 5752 publications have been published receiving 152029 citations. The journal is also known as: J. Inherit. Metab. Dis..

A general introduction to the biochemistry of mitochondrial fatty acid β-oxidation

Abstract: Over the years, the mitochondrial fatty acid β-oxidation (FAO) pathway has been characterised at the biochemical level as well as the molecular biological level. FAO plays a pivotal role in energy homoeostasis, but it competes with glucose as the primary oxidative substrate. The mechanisms behind this so-called glucose–fatty acid cycle operate at the hormonal, transcriptional and biochemical levels. Inherited defects for most of the FAO enzymes have been identified and characterised and are currently included in neonatal screening programmes. Symptoms range from hypoketotic hypoglycaemia to skeletal and cardiac myopathies. The pathophysiology of these diseases is still not completely understood, hampering optimal treatment. Studies of patients and mouse models will contribute to our understanding of the pathogenesis and will ultimately lead to better treatment.

Blood-brain barrier structure and function and the challenges for CNS drug delivery.

Abstract: The neurons of the central nervous system (CNS) require precise control of their bathing microenvironment for optimal function, and an important element in this control is the blood–brain barrier (BBB). The BBB is formed by the endothelial cells lining the brain microvessels, under the inductive influence of neighbouring cell types within the ‘neurovascular unit’ (NVU) including astrocytes and pericytes. The endothelium forms the major interface between the blood and the CNS, and by a combination of low passive permeability and presence of specific transport systems, enzymes and receptors regulates molecular and cellular traffic across the barrier layer. A number of methods and models are available for examining BBB permeation in vivo and in vitro, and can give valuable information on the mechanisms by which therapeutic agents and constructs permeate, ways to optimize permeation, and implications for drug discovery, delivery and toxicity. For treating lysosomal storage diseases (LSDs), models can be included that mimic aspects of the disease, including genetically-modified animals, and in vitro models can be used to examine the effects of cells of the NVU on the BBB under pathological conditions. For testing CNS drug delivery, several in vitro models now provide reliable prediction of penetration of drugs including large molecules and artificial constructs with promising potential in treating LSDs. For many of these diseases it is still not clear how best to deliver appropriate drugs to the CNS, and a concerted approach using a variety of models and methods can give critical insights and indicate practical solutions.

Tandem mass spectrometry: A new method for acylcarnitine profiling with potential for neonatal screening for inborn errors of metabolism

Abstract: A method for analysis of acylcarnitines in blood at physiological concentrations has been developed Preliminary results from umbilical cord blood and neonatal blood spotted onto Guthrie cards are encouraging This method will detect up to at least eight inherited metabolic disorders which exhibit diagnostic acylcarnitine profiles, including medium-chain acyl-CoA dehydrogenase deficiency The speed and simplicity of the method permit automation with existing technology, and could enable routine neonatal screening to be carried out in an efficient and cost-effective manner

Long-term prognosis in galactosaemia: results of a survey of 350 cases.

Abstract: An international survey of the long term results of treating galactosaemia has shown poor results. These do not seem to be related to any of the relevant variables studied, for example delayed diagnosis or poor dietary compliance.

Mitochondrial ATP synthase: architecture, function and pathology

Abstract: Human mitochondrial (mt) ATP synthase, or complex V consists of two functional domains: F1, situated in the mitochondrial matrix, and Fo, located in the inner mitochondrial membrane. Complex V uses the energy created by the proton electrochemical gradient to phosphorylate ADP to ATP. This review covers the architecture, function and assembly of complex V. The role of complex V di-and oligomerization and its relation with mitochondrial morphology is discussed. Finally, pathology related to complex V deficiency and current therapeutic strategies are highlighted. Despite the huge progress in this research field over the past decades, questions remain to be answered regarding the structure of subunits, the function of the rotary nanomotor at a molecular level, and the human complex V assembly process. The elucidation of more nuclear genetic defects will guide physio(patho)logical studies, paving the way for future therapeutic interventions.