'It is even so Nature is nowhere accustomed more openly to display her secret mysteries than in cases where she shows traces ofher workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by careful investigation of cases of rarer forms of disease. For it has been found in almo...

By their very nature, rare inborn errors of metabolism challenge the generation and application of evidence-based medicine. • On the basis of limited research evidence as well as consensus, newborn screening for select metabolic disorders, including phenylketonuria, medium-chain acyl CoA dehydrogenase deficiency, and glutaric acidemia type I, may improve long-term outcomes for affected children...

The introduction of experimental treatment for lysosomal storage disorders and the increasing understanding of the molecular defects behind many inborn errors have overshadowed the fact that for many affected families the best that can be offered is a rapid, accurate prenatal diagnostic service. Many conditions remain at best only partially treatable and as a consequence the majority of parents...

Inborn errors of metabolism (IEMs) are a vast, diverse, and heterogeneous set of genetic disorders. Hepatic-based IEMs are a significant cause of morbidity and mortality, and represent a common indication for liver transplantation (LTx) in the paediatric population. This review focuses on four of the most common hepatic-based IEMs where Tx, either as whole organ liver or as isolated hepatocytes...

Although essential fructosuria has been known for 70 years and has been recognized as an inborn error of metabolism for more than 20 years (Lasker, 1941), it is only recently that a second metabolic anomaly involving fructose has been described by Froesch, Prader, Labhart, Stuber and Wolf (1957). These authors recorded four affected (two children and two adults) and three probably affected memb...

CONTEXT Inborn errors of metabolism cause hereditary metabolic diseases (HMD) and classically they result from the lack of activity of one or more specific enzymes or defects in the transportation of proteins. OBJECTIVES A clinical review of inborn errors of metabolism (IEM) to give a practical approach to the physician with figures and tables to help in understanding the more common groups o...

Seizures may be the first and the major presenting feature of an inborn error of metabolism (IEM), for example in a neonate with pyridoxine-dependent epilepsy. In other IEMs, seizures may be preceded by other major symptoms: by a reduced level of consciousness in a child with an organic acidaemia or urea cycle defect; or by loss of skills, progressive weakness, ataxia, and upper motor signs in ...

Mitochondria play a pivotal role in cellular metabolism and in energy production in particular. Predictably, defects of mitochondrial metabolism have a deleterious effect on cell function and survival, especially in highly energy-dependent tissues such as brain and skeletal muscle. Although a multitude of biochemical reactions occur within mitochondria, the oxidative phosphorylation (OXPHOS) sy...

Cystinuria (OMIM 220100) is an inborn congenital disorder characterised by a defective cystine metabolism resulting in the formation of cystine stones. Among the heterogeneous group of kidney stone diseases, cystinuria is the only disorder which is exclusively caused by gene mutations. So far, two genes responsible for cystinuria have been identified: SLC3A1 (chromosome 2p21) encodes the heavy ...