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.

Inborn errors of metabolism and the human interactome: a systems medicine approach
AbstractThe group of inborn errors of metabolism (IEM) displays a marked heterogeneity and IEM can affect virtually all functions and organs of the human organism; however, IEM share that their associated proteins function in metabolism. Most proteins carry out cellular functions by interacting with other proteins, and thus are organized in biological networks. Therefore, diseases are rarely the consequence of single gene mutations but of the perturbations caused in the related cellular network. Systematic approaches that integrate multi-omics and database information into biological networks have successfully expanded our...
Source: Journal of Inherited Metabolic Disease - February 5, 2018 Category: Internal Medicine Source Type: research

Transplantation as disease modifying therapy in adults with inherited metabolic disorders
AbstractTransplantation is an established disease modifying therapy in selected children with certain inherited metabolic diseases (IMDs). Transplantation of hematopoietic stem cells or solid organs can be used to partially correct the underlying metabolic defect, address life threatening disease manifestations (such as neutropenia) or correct organ failure caused by the disease process. Much less information is available on the use of transplantation in adults with IMDs. Transplantation is indicated for the same IMDs in adults as in children. Despite similar disease specific indications, the actual spectrum of diseases fo...
Source: Journal of Inherited Metabolic Disease - February 1, 2018 Category: Internal Medicine Source Type: research

Keeping an eye on congenital disorders of O-glycosylation: a systematic literature review
AbstractCongenital disorders of glycosylation (CDG) are a rapidly growing family comprising>100 genetic diseases. Some 25 CDG are pure O-glycosylation defects. Even among this CDG subgroup, phenotypic diversity is broad, ranging from mild to severe poly-organ/system dysfunction. Ophthalmic manifestations are present in 60% of these CDG. The ophthalmic manifestations in N-glycosylation-deficient patients have been described elsewhere. The present review documents the spectrum and incidence of eye disorders in patients with pure O-glycosylation defects with the aim of assisting diagnosis and management and promoting resea...
Source: Journal of Inherited Metabolic Disease - February 1, 2018 Category: Internal Medicine Source Type: research

Timing of cognitive decline in CLN3 disease
ConclusionsCognitive dysfunction is universally present around diagnosis in classical CLN3 disease. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - February 1, 2018 Category: Internal Medicine Source Type: research

“Transcriptomics”: molecular diagnosis of inborn errors of metabolism via RNA-sequencing
AbstractExome wide sequencing techniques have revolutionized molecular diagnostics in patients with suspected inborn errors of metabolism or neuromuscular disorders. However, the diagnostic yield of 25 –60% still leaves a large fraction of individuals without a diagnosis. This indicates a causative role for non-exonic regulatory variants not covered by whole exome sequencing. Here we review how systematic RNA-sequencing analysis (RNA-seq, “transcriptomics”) lead to a molecular diagnosis in 1 0–35% of patients in whom whole exome sequencing failed to do so. Importantly, RNA-sequencing based discoveries cannot only g...
Source: Journal of Inherited Metabolic Disease - January 25, 2018 Category: Internal Medicine Source Type: research

A mild case of molybdenum cofactor deficiency defines an alternative route of MOCS1 protein maturation
AbstractMolybdenum cofactor deficiency is an autosomal recessive inborn error of metabolism, which results from mutations in genes involved in Moco biosynthesis. Moco serves as a cofactor of several enzymes, including sulfite oxidase. MoCD is clinically characterized by intractable seizures and severe, rapidly progressing neurodegeneration leading to death in early childhood in the majority of known cases. Here we report a patient with an unusual late disease onset and mild phenotype, characterized by a lack of seizures, normal early development, a decline triggered by febrile illness and a subsequent dystonic movement dis...
Source: Journal of Inherited Metabolic Disease - January 24, 2018 Category: Internal Medicine Source Type: research

The role of the clinician in the multi-omics era: are you ready?
AbstractSince Garrod ’s first description of alkaptonuria in 1902, and newborn screening for phenylketonuria introduced in the 1960s, P4 medicine (preventive, predictive, personalized, and participatory) has been a reality for the clinician serving patients with inherited metabolic diseases. The era of high-throughput technologies promises to accelerate its scale dramatically. Genomics, transcriptomics, epigenomics, proteomics, glycomics, metabolomics, and lipidomics offer an amazing opportunity for holistic investigation and contextual pathophysiologic understanding of inherited metabolic diseases for precise d iagnosis...
Source: Journal of Inherited Metabolic Disease - January 23, 2018 Category: Internal Medicine Source Type: research

Biochemical changes and clinical outcomes in 34 patients with classic galactosemia
This study evaluates clinical outcomes in 34 galactosemia patients with markedly reduced GALT activity and compares outcomes between patients with different levels of mean galactose-1-phosphate in red blood cells (GAL1P) using logistic regression: group 1 (n = 13) GAL1P ≤1.7 mg/dL vs. group 2 (n = 21) GAL1P ≥ 2 mg/dL. Acute symptoms at birth were comparable between groups (p = 0.30) with approximately 50% of patients presenting with jaundice, liver failure, and failure-to-thrive. However, group 2 patients had significantly higher prevalence of negative long-term outcomes compared to group 1 patients (...
Source: Journal of Inherited Metabolic Disease - January 19, 2018 Category: Internal Medicine Source Type: research

Text-based phenotypic profiles incorporating biochemical phenotypes of inborn errors of metabolism improve phenomics-based diagnosis
AbstractPhenomics is the comprehensive study of phenotypes at every level of biology: from metabolites to organisms. With high throughput technologies increasing the scope of biological discoveries, the field of phenomics has been developing rapid and precise methods to collect, catalog, and analyze phenotypes. Such methods have allowed phenotypic data to be widely used in medical applications, from assisting clinical diagnoses to prioritizing genomic diagnoses. To channel the benefits of phenomics into the field of inborn errors of metabolism (IEM), we have recently launched IEMbase, an expert-curated knowledgebase of IEM...
Source: Journal of Inherited Metabolic Disease - January 16, 2018 Category: Internal Medicine Source Type: research

Organic acidurias in adults: late complications and management
AbstractOrganic acidurias (synonym, organic acid disorders, OADs) are a heterogenous group of inherited metabolic diseases delineated with the implementation of gas chromatography/mass spectrometry in metabolic laboratories starting in the 1960s and 1970s. Biochemically, OADs are characterized by accumulation of mono-, di- and/or tricarboxylic acids ( “organic acids”) and corresponding coenzyme A, carnitine and/or glycine esters, some of which are considered toxic at high concentrations. Clinically, disease onset is variable, however, affected individuals may already present during the newborn period with life-threaten...
Source: Journal of Inherited Metabolic Disease - January 15, 2018 Category: Internal Medicine Source Type: research

Correction to: Age at disease onset and peak ammonium level rather than interventional variables predict the neurological outcome in urea cycle disorders
AbstractDue to an unfortunate error during the typesetting process, the collaborators were presented incorrectly. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - January 12, 2018 Category: Internal Medicine Source Type: research

Flux analysis of inborn errors of metabolism
In conclusion, the outlook for flux analysis of metabolic derangement in IEMs looks promising. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - January 9, 2018 Category: Internal Medicine Source Type: research

Olipudase alfa for treatment of acid sphingomyelinase deficiency (ASMD): safety and efficacy in adults treated for 30 months
This study demonstrates that treatment with olipudase alfa for 30 months is well-tolerated and associated with life-transforming sustained improvem ents in relevant disease clinical measures. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - January 5, 2018 Category: Internal Medicine Source Type: research

Chemical glycomics enrichment: imaging the recycling of sialic acid in living cells
AbstractThe development of metabolic oligosaccharide engineering (MOE) over the past two decades enabled the bioimaging studies of glycosylation processes in physio-pathological contexts. Herein, we successfully applied the chemical reporter strategy to image the fate of sialylated glycoconjugates in healthy and sialin-deficient patient fibroblasts. This chemical glycomics enrichment is a powerful tool for tracking sialylated glycoconjugates and probing lysosomal recycling capacities. Thus, such strategies appear fundamental for the characterization of lysosomal storage diseases. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - January 2, 2018 Category: Internal Medicine Source Type: research

Globotriaosylsphingosine (Lyso-Gb 3 ) as a biomarker for cardiac variant (N215S) Fabry disease
AbstractFabry disease (FD) is a multi-systemic X-linked lysosomal disorder caused by the deficient activity of α-galactosidase-A enzyme, which leads to accumulation of glycosphingolipids in various body tissues. The N215S mutation is a known variant of FD, with a late onset cardiac phenotype. Consensus guidelines acknowledged the use of globotriaosylsphingosine (Lyso-Gb3) as a diagnostic marker for classical FD but its utility for cardiac variant FD is not clear. We aim to characterize the clinical features and evaluate the diagnostic accuracy of plasma and urinary Lyso-Gb3 levels in N215S cardiac variant FD patients. Thi...
Source: Journal of Inherited Metabolic Disease - January 2, 2018 Category: Internal Medicine Source Type: research