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.

Molecular therapy of primary hyperoxaluria
AbstractDuring the last few decades, the molecular understanding of the mechanisms involved in primary hyperoxalurias (PHs) has set the stage for novel therapeutic approaches. The availability of PH mouse models has facilitated preclinical studies testing innovative treatments. PHs are autosomal recessive diseases where the enzymatic deficit plays a central pathogenic role. Thus, molecular therapies aimed at restoring such deficit or limiting the consequences of the metabolic derangement could be envisioned, keeping in mind the specific challenges posed by the cell-autonomous nature of the deficiency. Various molecular app...
Source: Journal of Inherited Metabolic Disease - July 1, 2017 Category: Internal Medicine Source Type: research

Hyperinsulinemic hypoglycemia: clinical, molecular and therapeutical novelties
AbstractHyperinsulinemic hypoglycemia (HI) is the most common cause of hypoglycemia in children. Impairment of cellular pathways involved in insulin secretion from pancreatic β-cells, broadly classified as channelopathies and metabolopathies, have been discovered in the past two decades. The increasing use of NGS target panels, combined with clinical, biochemical and imaging findings allows differentiating the diagnostic management of children with focal forms, surgical ly curable, from those with diffuse forms, more conservatively treated with pharmacological and nutritional interventions. Specific approaches according t...
Source: Journal of Inherited Metabolic Disease - June 27, 2017 Category: Internal Medicine Source Type: research

Amino acid synthesis deficiencies
AbstractIn recent years the number of disorders known to affect amino acid synthesis has grown rapidly. Nor is it just the number of disorders that has increased: the associated clinical phenotypes have also expanded spectacularly, primarily due to the advances of next generation sequencing diagnostics. In contrast to the “classical” inborn errors of metabolism in catabolic pathways, in which elevated levels of metabolites are easily detected in body fluids, synthesis defects present with low values of metabolites or, confusingly, even completely normal levels of amino acids. This makes the biochemical diagnosis of thi...
Source: Journal of Inherited Metabolic Disease - June 26, 2017 Category: Internal Medicine Source Type: research

News and views
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 26, 2017 Category: Internal Medicine Source Type: research

Erratum to: What is new in CDG?
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 26, 2017 Category: Internal Medicine Source Type: research

Cysteamine revisited: repair of arginine to cysteine mutations
AbstractCysteamine is a small aminothiol endogenously derived from coenzyme A degradation. For some decades, synthetic cysteamine has been employed for the treatment of cystinosis, and new uses of the drug continue to emerge. In this review, we discuss the role of cysteamine in cellular and extracellular homeostasis and focus on the potential use of aminothiols to reconstitute the function of proteins harboring arginine (Arg) to cysteine (Cys) mutations, via repair of the Cys residue into a moiety that introduces an amino group, as seen in basic amino acid residues Lys and Arg. Cysteamine has been utilized in vitro and ex ...
Source: Journal of Inherited Metabolic Disease - June 22, 2017 Category: Internal Medicine Source Type: research

Tight metabolic control plus ACE inhibitor therapy improves GSD I nephropathy
AbstractThe onset of microalbuminuria (MA) heralds the onset of glomerulopathy in patients with glycogen storage disease (GSD) type I. Unlike tubulopathy, which responds to improved metabolic control, glomerulopathy in GSD I is considered refractory to medical intervention, and it is thought to inexorably progress to overt proteinuria and renal failure. Recent reports of reduced microalbuminuria following strict adherence to therapy counter this view. In contrast to type Ia, little is known regarding the prevalence of kidney disease in GSD Ib, 0, III, VI, and IX. Subjects were evaluated with 24-h urine collections between ...
Source: Journal of Inherited Metabolic Disease - June 13, 2017 Category: Internal Medicine Source Type: research

Erratum to: Longitudinal volumetric and 2D assessment of cerebellar atrophy in a large cohort of children with phosphomannomutase deficiency (PMM2-CDG)
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 9, 2017 Category: Internal Medicine Source Type: research

High-content drug screening for rare diseases
AbstractPer definition, rare diseases affect only a small number of subjects within a given population. Taken together however, they represent a considerable medical burden, which remains poorly addressed in terms of treatment. Compared to other diseases, obstacles to the development of therapies for rare diseases include less extensive physiopathology knowledge, limited number of patients to test treatments, and poor commercial interest from the industry. Recently, advances in high-throughput and high-content screening (HTS and HCS) have been fostered by the development of specific routines that use robot- and computer-as...
Source: Journal of Inherited Metabolic Disease - June 7, 2017 Category: Internal Medicine Source Type: research

News and views
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - June 7, 2017 Category: Internal Medicine Source Type: research

Gene therapy for monogenic liver diseases: clinical successes, current challenges and future prospects
AbstractOver the last decade, pioneering liver-directed gene therapy trials for haemophilia B have achieved sustained clinical improvement after a single systemic injection of adeno-associated virus (AAV) derived vectors encoding the human factor IX cDNA. These trials demonstrate the potential of AAV technology to provide long-lasting clinical benefit in the treatment of monogenic liver disorders. Indeed, with more than ten ongoing or planned clinical trials for haemophilia A and B and dozens of trials planned for other inherited genetic/metabolic liver diseases, clinical translation is expanding rapidly. Gene therapy is l...
Source: Journal of Inherited Metabolic Disease - May 31, 2017 Category: Internal Medicine Source Type: research

Hearing loss in children with Fabry disease
ConclusionA minority of children with FD show slight/mild or moderate to severe HL, but their hearing thresholds are poorer than the reference values for normal-hearing children. Clinical trials in FD children should demonstrate whether HL can be prevented or reversed by early treatment and should specifically study ultra-high frequencies. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - May 31, 2017 Category: Internal Medicine Source Type: research

Gene therapy for lysosomal storage disorders: recent advances for metachromatic leukodystrophy and mucopolysaccaridosis I
AbstractLysosomal storage diseases (LSDs) are rare inherited metabolic disorders characterized by a dysfunction in lysosomes, leading to waste material accumulation and severe organ damage. Enzyme replacement therapy (ERT) and haematopoietic stem cell transplant (HSCT) have been exploited as potential treatments for LSDs but pre-clinical and clinical studies have shown in some cases limited efficacy. Intravenous ERT is able to control the damage of visceral organs but cannot prevent nervous impairment. Depending on the disease type, HSCT has important limitations when performed for early variants, unless treatment occurs b...
Source: Journal of Inherited Metabolic Disease - May 30, 2017 Category: Internal Medicine Source Type: research

Short-chain acyl-CoA dehydrogenase deficiency: from gene to cell pathology and possible disease mechanisms
AbstractShort-chain acyl-CoA dehydrogenase deficiency (SCADD) is an inherited disorder of mitochondrial fatty acid oxidation that is characterized by the presence of increased butyrylcarnitine and ethylmalonic acid (EMA) concentrations in plasma and urine. Individuals with symptomatic SCADD may show relatively severe phenotype, while the majority of those who are diagnosed through newborn screening by tandem mass spectrometry may remain asymptomatic. As such, the associated clinical symptoms are very diverse, ranging from severe metabolic or neuromuscular disabilities to asymptomatic. Molecular analysis of affected individ...
Source: Journal of Inherited Metabolic Disease - May 17, 2017 Category: Internal Medicine Source Type: research

Developmental window of sensorineural deafness in biotinidase-deficient mice
AbstractBiotinidase deficiency is an autosomal recessively inherited disorder that results in the inability to recycle the vitamin, biotin. If untreated, the disorder can result in a range of neurological and cutaneous symptoms, including sensorineural deficits and deafness. To understand early mechanistic abnormalities that may precede more generalized and nonspecific effects of metabolic deficits such as weight loss and acidosis, we have analyzed auditory brainstem responses (ABRs) in biotinidase-deficient knockout (Btd−/−) mice in the periweaning period with or without dietary biotin supplementation. We find signifi...
Source: Journal of Inherited Metabolic Disease - May 17, 2017 Category: Internal Medicine Source Type: research