Corrigendum to Universal newborn screening: A roadmap for action molecular genetics and metabolism 124 (2018) 177–183
Publication date: Available online 20 June 2019Source: Molecular Genetics and MetabolismAuthor(s): C.P. Howson, B. Cedergren, R. Giugliani, P. Huhtinen, C.D. Padilla, C.S. Palubiak, M.D. Santos, I.V.D. Schwartz, B.L. Therrell, A. Umemoto, J. Wang, X. Zeng, X. Zhao, N. Zhong, E.R.B. McCabe (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 21, 2019 Category: Genetics & Stem Cells Source Type: research

Efficacy of low dose nitisinone in the management of alkaptonuria
We described the evolution HGA excretion and tyrosine evolution in 3 AKU patients treated by very low dosage of nitisinone with regards to their daily protein intakes. We also described the first pregnancy in an AKU patient treated by nitisinone.ResultsWe found mild clinical signs of alkaptonuria on vertebra MRI in two young adults and homogentisate deposition in teeth of a 5 years old girl. Very low dose of nitisinone (10% of present recommended dose: 0.2 mg/day) allowed to decrease homogentisic acid by>90% without increasing tyrosine levels above 500 μmol/ in these three patients.InterpretationsThe analysis o...
Source: Molecular Genetics and Metabolism - June 19, 2019 Category: Genetics & Stem Cells Source Type: research

Pegvaliase: Immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy
ConclusionsOverall, it was agreed that pegvaliase has a generally tolerable safety profile in adults with PKU. Importantly, the risk mitigation strategies utilized in the clinical trials were considered to support the continued use of key strategies for management in the commercial setting, such as a slow induction/titration dosing paradigm and premedication with H1-receptor antagonists. However, physicians and patients need to be aware of the risk of HAEs associated with pegvaliase; presence of a trained observer during early treatment may be beneficial in certain circumstances, and a requirement to carry auto-injectable ...
Source: Molecular Genetics and Metabolism - June 18, 2019 Category: Genetics & Stem Cells Source Type: research

Cover 2 / Ed. Board
Publication date: June 2019Source: Molecular Genetics and Metabolism, Volume 127, Issue 2Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 16, 2019 Category: Genetics & Stem Cells Source Type: research

Table of Contents
Publication date: June 2019Source: Molecular Genetics and Metabolism, Volume 127, Issue 2Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 16, 2019 Category: Genetics & Stem Cells Source Type: research

Current treatment for citrin deficiency during NICCD and adaptation/compensation stages: Strategy to prevent CTLN2
Publication date: Available online 15 June 2019Source: Molecular Genetics and MetabolismAuthor(s): Yoshiyuki Okano, Toshihiro Ohura, Osamu Sakamoto, Ayano InuiAbstractIdentification of the genes responsible for adult-onset type II citrullinemia (CTLN2) and citrin protein function have enhanced our understanding of citrin deficiency. Citrin deficiency is characterized by 1) neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD); 2) adaptation/compensation stage with unique food preference from childhood to adulthood; and 3) CTLN2. The treatment of NICCD aims to prevent the progression of cholestasis, and it i...
Source: Molecular Genetics and Metabolism - June 16, 2019 Category: Genetics & Stem Cells Source Type: research

The novel synonymous variant in LIPA gene affects splicing and causes lysosomal acid lipase deficiency
We report a novel synonymous homozygous variant c.600G > A in LIPA of a patient with LALD. Functional analysis of the patient cDNA and minigene assay revealed this variant as the cause of exonic cryptic splice site activation and 63 b.p. deletion in exon 6. To investigate the impact of this in-frame deletion on protein function, we performed 3D modeling of the human lysosomal acid lipase and showed the alteration of highly conservative region in close proximity to protein active site, which may completely eliminate the enzymatic activity. Using transcript specific real-time quantitative PCR method, we evaluated the ...
Source: Molecular Genetics and Metabolism - June 16, 2019 Category: Genetics & Stem Cells Source Type: research

5-Aminolevulinate synthase catalysis: The catcher in Heme biosynthesis
Publication date: Available online 13 June 2019Source: Molecular Genetics and MetabolismAuthor(s): Bosko M. Stojanovski, Gregory A. Hunter, Insung Na, Vladimir N. Uversky, Rays H.Y. Jiang, Gloria C. FerreiraAbstract5-Aminolevulinate (ALA) synthase (ALAS), a homodimeric pyridoxal-5′-phosphate (PLP)-dependent enzyme, catalyzes the first step of heme biosynthesis in metazoa, fungi and α-proteobacteria. In this review, we focus on the advances made in unraveling the mechanism of the ALAS-catalyzed reaction during the past decade. The interplay between the PLP cofactor and the protein moiety determines and modulates...
Source: Molecular Genetics and Metabolism - June 13, 2019 Category: Genetics & Stem Cells Source Type: research

Tandem mass spectrometry-based multiplex assays for α-mannosidosis and fucosidosis
Publication date: Available online 10 June 2019Source: Molecular Genetics and MetabolismAuthor(s): Arun Babu Kumar, Xinying Hong, Fan Yi, Tim Wood, Michael H. GelbAbstractMultiplex tandem mass spectrometry (MS/MS)-based enzyme activity assays for newborn screening (NBS) and diagnosis of lysosomal storage diseases (LSDs) in newborns, using dried blood spots (DBS) on newborn screening cards, have garnered much attention due to its sensitivity, high precision, and the capability to screen for an unprecedented number of diseases in a single assay. Herein we report the development of MS/MS-based enzyme assays for the diagnosis ...
Source: Molecular Genetics and Metabolism - June 10, 2019 Category: Genetics & Stem Cells Source Type: research

Circulating blood cellular glucose transporters – Surrogate biomarkers for neonatal hypoxic-ischemic encephalopathy assessed by novel scoring systems
We examined Red Blood Cell (RBC) Glucose Transporter isoform 1 (GLUT1) and White Blood Cell (WBC) Glucose Transporter isoform 3 (GLUT3) protein concentrations to assess their potential as surrogate biomarkers for the presence of hypoxic-ischemic encephalopathy (HIE) and response to therapeutic hypothermia (TH), with respect to the neurodevelopmental prognosis.Study designA prospective feasibility study of 10 infants with HIE and 8 age-matched control subjects was undertaken. Following parental consent, blood samples were obtained at baseline before institution of TH (
Source: Molecular Genetics and Metabolism - June 9, 2019 Category: Genetics & Stem Cells Source Type: research

Five-parameter evaluation of dysphagia: A novel prognostic scale for assessing neurological decline in Gaucher disease type 2
ConclusionA five-parameter swallow evaluation was sufficient to identify distinct states of GD2 and model prospective outcomes. This multi-dimensional evaluation could be a useful efficacy parameter for future therapeutic trials in GD2 and other neurodegenerative disorders of infancy. (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 9, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency
ConclusionsThe present study improves the knowledge of the natural history of HPRT deficiency and could represent a starting point for the development of future management guidelines. (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 4, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical characterization of tremor in patients with phenylketonuria
Publication date: Available online 3 June 2019Source: Molecular Genetics and MetabolismAuthor(s): Francesca Nardecchia, Filippo Manti, Sabrina De Leo, Claudia Carducci, Vincenzo LeuzziAbstractBackgroundPhenylketonuria (PKU) is due to the deficit of the enzyme phenylalanine hydroxylase, the first step of dopamine synthesis. If not early treated the disease results in severe neurological impairment. Minor neurological signs have been reported in early treated PKU (ETPKU) subjects. Prolactin level is affected by (and reflects) brain dopamine availability. Object of the study was to assess the occurrence, age at onset, distrib...
Source: Molecular Genetics and Metabolism - June 3, 2019 Category: Genetics & Stem Cells Source Type: research

Cover 2 / Ed. Board
Publication date: May 2019Source: Molecular Genetics and Metabolism, Volume 127, Issue 1Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 1, 2019 Category: Genetics & Stem Cells Source Type: research

Table of Contents
Publication date: May 2019Source: Molecular Genetics and Metabolism, Volume 127, Issue 1Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - June 1, 2019 Category: Genetics & Stem Cells Source Type: research

Circulating blood cellular glucose transporters – Surrogate biomarkers for neonatal hypoxic ischemic encephalopathy assessed by novel scoring systems
We examined Red Blood Cell (RBC) Glucose Transporter isoform 1 (GLUT1) and White Blood Cell (WBC) Glucose Transporter isoform 3 (GLUT3) protein concentrations to assess their potential as surrogate biomarkers for the presence of hypoxic-ischemic encephalopathy (HIE) and response to therapeutic hypothermia (TH), with respect to the neurodevelopmental prognosis.Study designA prospective feasibility study of 10 infants with HIE and 8 age-matched control subjects was undertaken. Following parental consent, blood samples were obtained at baseline before institution of TH (
Source: Molecular Genetics and Metabolism - May 29, 2019 Category: Genetics & Stem Cells Source Type: research

Urinary 2,8-dihydroxyadenine excretion in patients with APRT deficiency, carriers and healthy control subjects
Publication date: Available online 28 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Hrafnhildur L. Runolfsdottir, Runolfur Palsson, Unnur A. Thorsteinsdottir, Olafur S. Indridason, Inger M.Sch. Agustsdottir, G. Steinunn Oddsdottir, Margret Thorsteinsdottir, Vidar O. EdvardssonAbstractBackgroundAdenine phosphoribosyltransferase (APRT) deficiency is a rare autosomal recessive disorder of adenine metabolism that results in excessive urinary excretion of the poorly soluble 2,8-dihydroxyadenine (DHA), leading to kidney stones and chronic kidney disease. The purpose of this study was to assess urinary DHA excretion...
Source: Molecular Genetics and Metabolism - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Genetic correction of induced pluripotent stem cells mediated by transcription activator-like effector nucleases targeting ALPL recovers enzyme activity and calcification in vitro
Publication date: Available online 28 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Chiho Nakano, Yasuji Kitabatake, Shinji Takeyari, Yasuhisa Ohata, Takuo Kubota, Ken Taketani, Mikihiko Kogo, Keiichi OzonoAbstractHypophosphatasia (HPP) is an inheritable disease affecting both skeletal systems and extra-skeletal organs due to mutations of the gene ALPL, which encodes tissue-nonspecific alkaline phosphatase. Recently, an enzyme replacement therapy using asfotase alfa was developed to ameliorate the complications of HPP. However, it requires frequent injections and is expensive to maintain. As an alternative, c...
Source: Molecular Genetics and Metabolism - May 28, 2019 Category: Genetics & Stem Cells Source Type: research

Harmonizing care for rare diseases: How we developed the mitochondrial care network in the United States
Publication date: Available online 23 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Amel Karaa, Amy Goldstein, Cristy Balcells, Kira Mann, Laura Stanley, Philip E. Yeske, Sumit ParikhAbstractThe mitochondrial medicine society (MMS) has previously highlighted the clinical landscape and physician practice patterns of mitochondrial medicine in the US and attempted to develop consensus criteria for diagnosis and management to improve patient coordinated care. Most recently, and in collaboration with US-based patient advocacy groups, we developed a clinical care network to formally unify US-based clinicians who pr...
Source: Molecular Genetics and Metabolism - May 24, 2019 Category: Genetics & Stem Cells Source Type: research

Murine models of the human porphyrias: Contributions toward understanding disease pathogenesis and the development of new therapies
Publication date: Available online 18 January 2019Source: Molecular Genetics and MetabolismAuthor(s): Makiko Yasuda, Robert J. DesnickAbstractMouse models of the human porphyrias have proven useful for investigations of disease pathogenesis and to facilitate the development of new therapeutic approaches. To date, mouse models have been generated for all major porphyrias, with the exception of X-linked protoporphyria (XLP) and the ultra rare 5-aminolevulinic acid dehydratase deficient porphyria (ADP). Mouse models have been generated for the three autosomal dominant acute hepatic porphyrias, acute intermittent porphyria (AI...
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Cover 2 / Ed. Board
Publication date: April 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 4Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Table of Contents
Publication date: April 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 4Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Metabolic analysis reveals evidence for branched chain amino acid catabolism crosstalk and the potential for improved treatment of organic acidurias
Publication date: Available online 21 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Stephen McCalley, David Pirman, Michelle Clasquin, Kendall Johnson, Shengfang Jin, Jerry VockleyAbstractBranched chain amino acid (BCAA) metabolism occurs within the mitochondrial matrix and is comprised of multiple enzymes, some shared, organized into three pathways for the catabolism of leucine, isoleucine, and valine (LEU, ILE, and VAL respectively). Three different acyl-CoA dehydrogenases (ACADs) are active in each catabolic pathway and genetic deficiencies in each have been identified. While characteristic metabolites rel...
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Gaucher disease type 3c: New patients with unique presentations and review of the literature
Publication date: Available online 21 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Alina Kurolap, Mireia del Toro, Ronen Spiegel, Ariel Gutstein, Gideon Shafir, Ian J. Cohen, José A. Barrabés, Hagit Baris FeldmanAbstractGaucher disease (GD) is the most prevalent lysosomal disorder caused by GBA mutations and abnormal glucocerebrosidase function, leading to glucocerebrosideaccumulation mainly in the liver, spleen, bone marrow, lungs, and occasionally in the central nervous system. Gaucher disease type 3c (GD3c) is a rare subtype of the subacute/chronic neuronopathic GD3, caused by homozygosity f...
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Tumor necrosis factor-α links heat and inflammation with Fabry pain
Publication date: Available online 20 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Nurcan Üçeyler, Daniela Urlaub, Christine Mayer, Sabrina Uehlein, Melissa Held, Claudia SommerAbstractFabry disease (FD) is an X-linked lysosomal storage disorder associated with pain triggered by heat or febrile infections. We modelled this condition by measuring the cytokine expression of peripheral blood mononuclear cells (PBMC) from FD patients in vitro upon stimulation with heat and lipopolysaccharide (LPS). We enrolled 67 FD patients and 37 healthy controls. We isolated PBMC, assessed their gene expression of...
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

Pilot study of mitochondrial bioenergetics in subjects with acute porphyrias
Publication date: Available online 20 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Natalia Dixon, Ting Li, Brandon Marion, Denise Faust, Stephen Dozier, Anthony Molina, Sean Rudnick, Herbert L. BonkovskyAbstractBackground and aimsThe acute porphyrias are characterized by defects in heme synthesis, particularly in the liver. In some affected patients, there occurs a critical deficiency in a regulatory heme pool within hepatocytes that leads to up-regulation of 5-aminolevulinic acid [ALA] synthase-1, which is the first and normally rate-controlling enzyme in the pathway. In earlier work, we described defects i...
Source: Molecular Genetics and Metabolism - May 22, 2019 Category: Genetics & Stem Cells Source Type: research

White matter lesions in treated late onset Pompe disease are not different to matched controls
ConclusionThe study suggests that WML in LOPD mainly result from concomitant cerebrovascular risk factors rather than from the Pompe disease itself. (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - May 15, 2019 Category: Genetics & Stem Cells Source Type: research

Evaluation of biomarkers for Sanfilippo syndrome
Publication date: Available online 9 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Jennifer T. Saville, Kevin M. Flanigan, Kristen V. Truxal, Kim L. McBride, Maria FullerAbstractSanfilippo syndrome or mucopolysaccharidosis type III (MPS III) is a childhood metabolic disorder marked by neuropathology arising due to impaired heparan sulphate (HS) catabolism. Consequently, partially degraded HS accumulates in the lysosomes of affected cells and is excreted in the urine. The measurement of HS in urine has long been considered a biomarker of Sanfilippo syndrome although it is largely non-specific. Using blood, uri...
Source: Molecular Genetics and Metabolism - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

Inborn errors of mitochondrial acyl-coenzyme a metabolism: acyl-CoA biology meets the clinic
Publication date: Available online 9 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Hao Yang, Chen Zhao, Marie-Christine Tang, Youlin Wang, Shu Pei Wang, Pierre Allard, Alexandra Furtos, Grant A. MitchellAbstractThe last decade saw major advances in understanding the metabolism of Coenzyme A (CoA) thioesters (acyl-CoAs) and related inborn errors (CoA metabolic diseases, CAMDs). For diagnosis, acylcarnitines and organic acids, both derived from acyl-CoAs, are excellent markers of most CAMDs. Clinically, each CAMD is unique but strikingly, three main patterns emerge: first, systemic decompensations with combinat...
Source: Molecular Genetics and Metabolism - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

Association between hepatitis C virus and porphyria cutanea tarda
Publication date: Available online 9 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Jordi To- FiguerasAbstractPorphyria cutanea tarda (PCT) arises from a deficiency of uroporphyrinogen decarboxylase (UROD) in the liver. Several exogenous risk factors are associated with the acquired form of the disease. In Southern Europe, PCT is strongly linked to hepatitis C virus (HCV) infection to the point that a high prevalence of viral infection in some geographic areas generated an increase of PCT cases as a complication. In spite of the association, PCT was a rare complication of HCV infection, thus suggesting the exi...
Source: Molecular Genetics and Metabolism - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

A novel compound heterozygous genotype associated with aromatic amino acid decarboxylase deficiency: Clinical aspects and biochemical studies
Publication date: Available online 10 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Riccardo Montioli, Roberta Battini, Alessandro Paiardini, Manuela Tolve, Mariarita Bertoldi, Carla Carducci, Vincenzo Leuzzi, Carla Borri VoltattorniAbstractAromatic amino acid decarboxylase (AADC) deficiency is a rare autosomal neurometabolic disorder caused by a deficit of AADC, a pyridoxal 5′-phosphate (PLP)-dependent enzyme, which catalyzes the synthesis of dopamine and serotonin. While many studies have highlighted the molecular defects of the homozygous pathogenic variants, so far only a study investigated heterozy...
Source: Molecular Genetics and Metabolism - May 10, 2019 Category: Genetics & Stem Cells Source Type: research

Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): A protocol for a sham-controlled clinical trial
Publication date: Available online 8 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Harrison N. Jones, Maragatha Kuchibhatla, Kelly D. Crisp, Lisa D. Hobson Webb, Laura Case, Milisa T. Batten, Jill A. Marcus, Richard M. Kravitz, Priya S. KishnaniAbstractIntroductionMorbidity and mortality in adults with late-onset Pompe disease (LOPD) results primarily from persistent progressive respiratory muscle weakness despite treatment with enzyme replacement therapy (ERT). To address this need, we have developed a 12-week respiratory muscle training (RMT) program that provides calibrated, individualized, and progressive...
Source: Molecular Genetics and Metabolism - May 8, 2019 Category: Genetics & Stem Cells Source Type: research

Lysine demethylases KDM6A and UTY: The X and Y of histone demethylation
Publication date: Available online 6 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Iveta Gažová, Andreas Lengeling, Kim M. SummersAbstractHistone demethylases remove transcriptional repressive marks from histones in the nucleus. KDM6A (also known as UTX) is a lysine demethylase which acts on the trimethylated lysine at position 27 in histone 3. The KDM6A gene is located on the X chromosome but escapes X inactivation even though it is not located in the pseudoautosomal region. There is a homologue of KDM6A on the Y chromosome, known as UTY. UTY was thought to have lost its demethylase activity and to r...
Source: Molecular Genetics and Metabolism - May 7, 2019 Category: Genetics & Stem Cells Source Type: research

Ganglioside GM2 catabolism is inhibited by storage compounds of mucopolysaccharidoses and by cationic amphiphilic drugs
Publication date: Available online 4 May 2019Source: Molecular Genetics and MetabolismAuthor(s): Susi Anheuser, Bernadette Breiden, Konrad SandhoffAbstractThe catabolism of ganglioside GM2 is dependent on the lysosomal enzyme β-hexosaminidase A and a supporting lipid transfer protein, the GM2 activator protein. A genetically based disturbance of GM2 catabolism, leads to several subtypes of the GM2 gangliosidosis: Tay-Sachs disease, Sandhoff disease, the AB-variant and the B1-variant, all of them having GM2 as major lysosomal storage compound.Further on it is known that the gangliosides GM2 and GM3 accumulate as second...
Source: Molecular Genetics and Metabolism - May 5, 2019 Category: Genetics & Stem Cells Source Type: research

Delta-aminolevulinic acid synthase 2 expression in combination with iron as modifiers of disease severity in erythropoietic protoporphyria
In this study, we demonstrated that iron deprivation increased the amount of ALAS2 mRNA as well as the ratio of ALAS2 to FECH mRNAs in cultured erythroleukemic K562 cells. At the protein level, however, iron deprivation in the cell line caused reductions in both enzymes as shown by the Western blot analysis. A comparable increase in the ratio of ALAS2 to FECH mRNAs was also found in EPP patients indicating an imbalance in heme biosynthesis. As iron cannot be completely missing from an organism, we assume that in EPP patients, a certain amount of ALAS2 mRNA is translated despite a partial deficiency of FECH. The increase in...
Source: Molecular Genetics and Metabolism - May 4, 2019 Category: Genetics & Stem Cells Source Type: research

International best practice for the evaluation of responsiveness to sapropterin dihydrochloride in patients with phenylketonuria
Publication date: Available online 26 April 2019Source: Molecular Genetics and MetabolismAuthor(s): Ania C. Muntau, Darius J. Adams, Amaya Bélanger-Quintana, Tatiana V. Bushueva, Roberto Cerone, Yin-Hsiu Chien, Ana Chiesa, Turgay Coşkun, Javier de las Heras, François Feillet, Rachel Katz, Florian Lagler, Flavia Piazzon, Fran Rohr, Francjan J. van Spronsen, Paula Vargas, Gisela Wilcox, Kaustuv BhattacharyaAbstractPhenylketonuria (PKU) is an inherited metabolic disease caused by phenylalanine hydroxylase (PAH) deficiency. As the resulting high blood phenylalanine (Phe) concentration can have detrimental effect...
Source: Molecular Genetics and Metabolism - April 28, 2019 Category: Genetics & Stem Cells Source Type: research

Analysis of fragment size distribution of cell-free DNA: A potential non-invasive marker to monitor graft damage in living-related liver transplantation for inborn errors of metabolism
In this study, eleven patients diagnosed with different inborn errors of metabolism (IEMs) who required living-related LTx were enrolled in order to establish a potentially useful noninvasive method to monitor graft damage. Circulating cell-free DNA (cfDNA) was extracted from plasma specimens serially collected at specific time points (day 0, day 1, day 7, day 14, day 30, day 60) after LTx. The distribution of Gcf-DNA fragment sizes was measured using sequencing read lengths and quantified by using Y-chromosome capture methodology in seven sex-mismatched recipients. In the analysis of fragment size distribution, we observe...
Source: Molecular Genetics and Metabolism - April 25, 2019 Category: Genetics & Stem Cells Source Type: research

Heme biosynthesis and the porphyrias
Publication date: Available online 22 April 2019Source: Molecular Genetics and MetabolismAuthor(s): John D. PhillipsAbstractPorphyrias, is a general term for a group of metabolic diseases that are genetic in nature. In each specific porphyria the activity of specific enzymes in the heme biosynthetic pathway is defective and leads to accumulation of pathway intermediates. Phenotypically, each disease leads to either neurologic and/or photocutaneous symptoms based on the metabolic intermediate that accumulates. In each porphyria the distinct patterns of these substances in plasma, erythrocytes, urine and feces are the basis ...
Source: Molecular Genetics and Metabolism - April 23, 2019 Category: Genetics & Stem Cells Source Type: research

A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in border collies and Australian cattle dogs
Publication date: Available online 17 April 2019Source: Molecular Genetics and MetabolismAuthor(s): Natalie A. Villani, Garrett Bullock, Jennifer R. Michaels, Osamu Yamato, Dennis P. O'Brien, Tendai Mhlanga-Mutangadura, Gary S. Johnson, Martin L. KatzAbstractThe neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by progressive declines in neurological functions following normal development. The NCLs are distinguished from similar disorders by the accumulation of autofluorescent lysosomal storage bodies in neurons and many other cell types, and are classified as lysosoma...
Source: Molecular Genetics and Metabolism - April 19, 2019 Category: Genetics & Stem Cells Source Type: research

Inter-assay variability influences migalastat amenability assessments among Fabry disease variants
In this study, the reproducibility of the amenability assay was assessed by evaluation of 59 GLA variants for α-Gal A activity in the presence and absence of migalastat. As for the GLP-HEK assay, variants were considered amenable when there was both an absolute increase in enzyme activity of ≥3% wild-type and a relative increase in enzyme activity ≥1.2 fold over baseline following incubation with migalastat. Six of the 59 variants tested here did not match the classification of amenability reported using the GLP-HEK assay. Linear regression and Bland-Altman analyses, comparing data from all variants with and wi...
Source: Molecular Genetics and Metabolism - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical and biochemical outcome of patients with very long-chain acyl-CoA dehydrogenase deficiency
DiscussionVLCAD deficiency can be identified by neonatal screening. Most patients compliant with therapy normalized biochemical parameters and had no major clinical manifestations. Complications were completely prevented with a relatively low number of pre-emptive ER visits or hospital admissions. It remains unclear whether neonatal screening is now identifying less severely affected patient or if complications will arise as subjects become older. Observation beyond puberty is necessary to fully understand the impact of VLCAD deficiency on morbidity in patients with VLCAD deficiency. (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - April 16, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical and biochemical footprints of inherited metabolic diseases. II. Metabolic liver diseases
Publication date: Available online 12 April 2019Source: Molecular Genetics and MetabolismAuthor(s): Carlos R. Ferreira, David Cassiman, Nenad BlauAbstractInherited metabolic diseases account for about one third of pediatric patients with hepatomegaly, acute liver failure, cirrhosis or cholestasis. Specifically for pediatric acute liver failure, they account for 10–15% of cases, with a mortality of 22–65%. The percentage of acute liver failure caused by an inherited metabolic disease in children
Source: Molecular Genetics and Metabolism - April 13, 2019 Category: Genetics & Stem Cells Source Type: research

Low-dose agalsidase beta treatment in male pediatric patients with Fabry disease: A 5-year randomized controlled trial
ConclusionsOur findings increase the limited amount of available data on long-term effects of enzyme replacement therapy in pediatric, classic Fabry patients. The low-dose regimens studied here over a period of 5 years did not demonstrate a consistent benefit among the patients in terms of controlling symptomatology, urine GL-3 levels, and pathological histology. The current available evidence supports treatment of pediatric, classic male Fabry patients at the approved agalsidase beta dose of 1.0 mg/kg 2-weekly if these patients are considered for enzyme replacement therapy with agalsidase beta. (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - April 5, 2019 Category: Genetics & Stem Cells Source Type: research

ATP13A2 missense variant in Australian Cattle Dogs with late onset neuronal ceroid lipofuscinosis
Publication date: Available online 27 March 2019Source: Molecular Genetics and MetabolismAuthor(s): Isabelle Schmutz, Vidhya Jagannathan, Florian Bartenschlager, Veronika M. Stein, Achim D. Gruber, Tosso Leeb, Martin KatzAbstractThe neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage disorders characterized by progressive neurodegeneration and declines in neurological functions. Pathogenic sequence variants in at least 13 genes underlie different forms of NCL, almost all of which are recessively inherited. To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breed...
Source: Molecular Genetics and Metabolism - March 28, 2019 Category: Genetics & Stem Cells Source Type: research

Aromatic amino acid decarboxylase deficiency: Molecular and metabolic basis and therapeutic outlook
Publication date: Available online 27 March 2019Source: Molecular Genetics and MetabolismAuthor(s): Nastassja Himmelreich, Riccardo Montioli, Mariarita Bertoldi, Carla Carducci, Vincenzo Leuzzi, Corinne Gemperle, Todd Berner, Keith Hyland, Beat Thöny, Georg F. Hoffmann, Carla B. Voltattorni, Nenad BlauAbstractAromatic-l-amino acid decarboxylase (AADC) deficiency is an ultra-rare inherited autosomal recessive disorder characterized by sharply reduced synthesis of dopamine as well as other neurotransmitters. Symptoms, including hypotonia and movement disorders (especially oculogyric crisis and dystonia) as well as auton...
Source: Molecular Genetics and Metabolism - March 28, 2019 Category: Genetics & Stem Cells Source Type: research

Clinical and biochemical footprints of inherited metabolic diseases. I. Movement disorders
Publication date: Available online 26 March 2019Source: Molecular Genetics and MetabolismAuthor(s): Carlos R. Ferreira, Georg F. Hoffmann, Nenad BlauAbstractAbout a third of patients with inherited metabolic diseases with neurologic involvement suffer from a movement disorder, in the form of ataxia, hyperkinetic movements, or hypokinetic-rigid syndrome. We reviewed and updated the list of known metabolic etiologies associated with various types of movement disorders, and found approximately 200 relevant inborn errors of metabolism. This represents the first of a series of articles attempting to create and maintain a compre...
Source: Molecular Genetics and Metabolism - March 27, 2019 Category: Genetics & Stem Cells Source Type: research

This manuscript is published in Molecular Genetics and Metabolism Reports -Volume 19,June 2019,p100454
Publication date: March 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 3Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - March 21, 2019 Category: Genetics & Stem Cells Source Type: research

This manuscript is published in Molecular Genetics and Metabolism -Volume 124,July 2018,p189-203
Publication date: March 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 3Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - March 21, 2019 Category: Genetics & Stem Cells Source Type: research

Cover 2 / Ed. Board
Publication date: March 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 3Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - March 21, 2019 Category: Genetics & Stem Cells Source Type: research

Table of Contents
Publication date: March 2019Source: Molecular Genetics and Metabolism, Volume 126, Issue 3Author(s): (Source: Molecular Genetics and Metabolism)
Source: Molecular Genetics and Metabolism - March 21, 2019 Category: Genetics & Stem Cells Source Type: research