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.

Proposed recommendations for diagnosing and managing individuals with glutaric aciduria type I: second revision
AbstractGlutaric aciduria type I (GA-I; synonym, glutaric acidemia type I) is a rare inherited metabolic disease caused by deficiency of glutaryl-CoA dehydrogenase located in the catabolic pathways of L-lysine, L-hydroxylysine, and L-tryptophan. The enzymatic defect results in elevated concentrations of glutaric acid, 3-hydroxyglutaric acid, glutaconic acid, and glutaryl carnitine in body tissues, which can be reliably detected by gas chromatography/mass spectrometry (organic acids) and tandem mass spectrometry (acylcarnitines). Most untreated individuals with GA-I experience acute encephalopathic crises during the first 6...
Source: Journal of Inherited Metabolic Disease - November 15, 2016 Category: Internal Medicine Source Type: research

Antenatal manifestations of inborn errors of metabolism: prenatal imaging findings
AbstractPrenatal manifestations of inborn errors of metabolism (IEM) are related to severe disorders involving metabolic pathways active in the fetal period and not compensated by maternal or placental metabolism. Some prenatal imaging findings can be suggestive of such conditions —especially in cases of consanguinity and/or recurrence of symptoms—after exclusion of the most frequent nonmetabolic etiologies. Most of these prenatal imaging findings are nonspecific. They include mainly ascites and hydrops fetalis, intrauterine growth restriction (IUGR), central nervous syst em (CNS) anomalies, echogenic kidneys, epiphyse...
Source: Journal of Inherited Metabolic Disease - November 15, 2016 Category: Internal Medicine Source Type: research

The galactosemia network (GalNet)
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 10, 2016 Category: Internal Medicine Source Type: research

Slow, continuous enzyme replacement via spinal CSF in dogs with the paediatric-onset neurodegenerative disease, MPS IIIA
AbstractIntra-cerebrospinal fluid (CSF) injection of recombinant human lysosomal enzyme is a potential treatment strategy for several neurodegenerative lysosomal storage disorders including Sanfilippo syndrome (Mucopolysaccharidosis type IIIA; MPS IIIA). Here we have utilised the MPS IIIA Huntaway dog model to compare the effectiveness of the repeated intermittent bolus injection strategy being used in the trials with an alternate approach; slow, continual infusion of replacement enzyme (recombinant human sulphamidase; rhSGSH) into the spinal CSF using a SynchroMed II ® pump attached to a spinal infusion cannula. The abil...
Source: Journal of Inherited Metabolic Disease - November 9, 2016 Category: Internal Medicine Source Type: research

Household financial burden of phenylketonuria and its impact on treatment in China: a cross-sectional study
ConclusionsThe management of PKU is associated with a severe financial burden on patients ’ families, which may lead to insufficient treatment or variation of blood Phe concentration. The current reimbursement policies are as yet inadequate. A national reimbursement system targeting treatment practices for PKU patients and other rare diseases across China is imperative. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 9, 2016 Category: Internal Medicine Source Type: research

Herpetiform keratitis and palmoplantar hyperkeratosis: warning signs for Richner-Hanhart syndrome
We report on a a boy from Brazil who presented with bilateral keratitis secondary to RHS, which had earlier been misdiagnosed as herpes simplex keratitis. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 9, 2016 Category: Internal Medicine Source Type: research

Lethal neonatal hyperammonemia in severe ornithine transcarbamylase (OTC) deficiency compounded by large hepatic portosystemic shunt
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 9, 2016 Category: Internal Medicine Source Type: research

Ketones and inborn errors of metabolism: old friends revisited
(Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - November 8, 2016 Category: Internal Medicine Source Type: research

Assessment of ataxia phenotype in a new mouse model of galactose-1 phosphate uridylyltransferase (GALT) deficiency
In this study, we further assess the fidelity of this new mouse model by examining the animals for the manifestation of a common neurological sequela in human patients: cerebellar ataxia. The balance, grip strength, and motor coordination of GALT-deficient and wild-type mice were tested using a modified rotarod. The results were compared to composite phenotype scoring tests, typically used to evaluate neurological and motor impairment. The data demonstrated abnormalities with varying severity in the GALT-deficient mice. Mice of different ages were used to reveal the progressive nature of motor impairment. The varying sever...
Source: Journal of Inherited Metabolic Disease - October 24, 2016 Category: Internal Medicine Source Type: research

Guidelines for the diagnosis and management of cystathionine beta-synthase deficiency
AbstractCystathionine beta-synthase (CBS) deficiency is a rare inherited disorder in the methionine catabolic pathway, in which the impaired synthesis of cystathionine leads to accumulation of homocysteine. Patients can present to many different specialists and diagnosis is often delayed. Severely affected patients usually present in childhood with ectopia lentis, learning difficulties and skeletal abnormalities. These patients generally require treatment with a low-methionine diet and/or betaine. In contrast, mildly affected patients are likely to present as adults with thromboembolism and to respond to treatment with pyr...
Source: Journal of Inherited Metabolic Disease - October 23, 2016 Category: Internal Medicine Source Type: research

Flunarizine rescues reduced lifespan in CLN3 triple knock-out Caenorhabditis elegans model of batten disease
AbstractCLN3 disease (Spielmeyer-Vogt-Sjogren-Batten disease, previously known as classic juvenile neuronal ceroid lipofuscinosis, NCL) is a pediatric-onset progressive neurodegenerative disease characterized by progressive vision loss, seizures, loss of cognitive and motor function, and early death. While no precise biochemical mechanism or therapies are known, the pathogenesis ofCLN3 disease involves intracellular calcium accumulation that may trigger apoptosis. Our prior work in in vitro cell models ofCLN3 deficiency suggested that FDA-approved calcium channel antagonists may have therapeutic value. To further evaluate ...
Source: Journal of Inherited Metabolic Disease - October 19, 2016 Category: Internal Medicine Source Type: research

Multicompartment analysis of protein-restricted phenylketonuric mice reveals amino acid imbalances in brain
ConclusionDepletion of taurine, glutamate, and serine in the brain of PKU mice with dietary protein restriction may provide new insight into neurocognitive deficits of PKU. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - October 18, 2016 Category: Internal Medicine Source Type: research

Impact of long-term elosulfase alfa treatment on respiratory function in patients with Morquio A syndrome
ConclusionsLong-term ERT is associated with sustained improvements in respiratory function in Morquio A. In younger patients ( ≤14 years), some improvement may be ascribed to growth. In older patients, other mechanisms, e.g., decreased glycosaminoglycan storage, are likely involved. (Source: Journal of Inherited Metabolic Disease)
Source: Journal of Inherited Metabolic Disease - October 14, 2016 Category: Internal Medicine Source Type: research

Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology
AbstractMucopolysaccharidosis type I (MPS IH) is a lysosomal storage disease (LSD) caused by inactivating mutations to the alpha-L-iduronidase (IDUA) gene. Treatment focuses on IDUA enzyme replacement and currently employed methods can be non-uniform in their efficacy particularly for the cardiac and craniofacial pathology. Therefore, we undertook efforts to better define the pathological cascade accounting for treatment refractory manifestations and demonstrate a role for the renin angiotensin system (RAS) using the IDUA−/− mouse model. Perturbation of the RAS in the aorta was more profound in male animals suggesting ...
Source: Journal of Inherited Metabolic Disease - October 13, 2016 Category: Internal Medicine Source Type: research

Functional characterization of missense mutations in severe methylenetetrahydrofolate reductase deficiency using a human expression system
Abstract5,10-Methylenetetrahydrofolate reductase (MTHFR) catalyzes the NADPH-dependent reduction of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate using FAD as the cofactor. Severe MTHFR deficiency is the most common inborn error of folate metabolism, resulting in hyperhomocysteinemia and homocystinuria. Approximately 70 missense mutations have been described that cause severe MTHFR deficiency, however, in most cases their mechanism of dysfunction remains unclear. Few studies have investigated mutational specific defects; most of these assessing only activity levels from a handful of mutations using heterologou...
Source: Journal of Inherited Metabolic Disease - October 13, 2016 Category: Internal Medicine Source Type: research