Journals Journal of Inherited Metabolic...

Journal of Inherited Metabolic Disease
Noa Rosenberg, Nina N Stolwijk, Sibren van den Berg, Joris J Heus, Vincent van der Wel, Teun van Gelder, Annet M Bosch, Saco J de Visser, Carla E M Hollak
Medicine development for rare diseases, including inborn errors of metabolism (IEMs) is challenging. Many academic innovations fail to reach the patient, either by stranding in the translational stage or due to suboptimal patient access related to pricing or uncertain effectiveness. Expanding and solidifying the role of the academic in public-private partnerships (PPPs) may present an innovative solution to help overcome these complexities. This narrative review explores the literature on traditional and novel collaborative approaches to medicine development for rare diseases and analyzes examples of PPPs, with a specific focus on IEMs...
March 20, 2023: Journal of Inherited Metabolic Disease
Yanhua Liu, Hans V Westerhoff
The inborn error of metabolism Phenylketonuria (PKU, OMIM 261600) is most often due to inactivation of phenylalanine hydroxylase (PAH), which converts phenylalanine (Phe) into tyrosine (Tyr). The reduced PAH activity increases blood concentration of phenylalanine and urine levels of phenylpyruvate. Flux Balance Analysis (FBA) of a single compartment model of PKU predicts that maximum growth rate should be reduced unless Tyr is supplemented. However, the PKU phenotype is lack of development of brain function specifically, and Phe reduction rather than Tyr supplementation cures the disease...
March 7, 2023: Journal of Inherited Metabolic Disease
Clément Pontoizeau, Clovis Gaborit, Nolan Tual, Marcelo Simon-Sola, Irina Rotaru, Marion Benoist, Pasqualina Colella, Antonin Lamazière, Anaïs Brassier, Jean-Baptiste Arnoux, Agnès Rötig, Chris Ottolenghi, Pascale de Lonlay, Federico Mingozzi, Marina Cavazzana, Manuel Schiff
Maple syrup urine disease (MSUD) is rare autosomal recessive metabolic disorder caused by the dysfunction of the mitochondrial branched-chain 2-ketoacid dehydrogenase (BCKD) enzyme complex leading to massive accumulation of branched-chain amino and 2-keto acids. MSUD management, based on a life-long strict protein restriction with non-toxic amino acids oral supplementation represents an unmet need as it is associated with a poor quality of life, and does not fully protect from acute life-threatening decompensations or long-term neuropsychiatric complications...
March 7, 2023: Journal of Inherited Metabolic Disease
Diego Martinelli, Giulio Catesini, Benedetta Greco, Alessia Guarnera, Chiara Parrillo, Evelina Maines, Daniela Longo, Antonio Napolitano, Francesca De Nictolis, Sara Cairoli, Daniela Liccardo, Stefania Caviglia, Anna Sidorina, Giorgia Olivieri, Barbara Siri, Roberto Bianchi, Gionata Spagnoletti, Luca Dello Strologo, Marco Spada, Carlo Dionisi-Vici
Liver and liver/kidney transplantation are increasingly used in methylmalonic aciduria, but little is known on their impact on CNS. The effect of transplantation on neurological outcome was prospectively assessed in six patients pre- and post-transplant by clinical evaluation and by measuring disease biomarkers in plasma and CSF, in combination with psychometric tests and brain MRI studies. Primary (methylmalonic- and methylcitric acid) and secondary biomarkers (glycine and glutamine) significantly improved in plasma, while they remained unchanged in CSF...
March 2, 2023: Journal of Inherited Metabolic Disease
Nathalie Guffon, Vassiliki Konstantopoulou, Julia B Hennermann, Nicole Muschol, Irene Bruno, Albina Tummolo, Ferdinando Ceravolo, Giulia Zardi, Andrea Ballabeni, Allan Lund
Alpha-mannosidosis (AM) is a rare, autosomal recessive, lysosomal storage disorder caused by alpha-mannosidase deficiency that leads to the accumulation of mannose-rich oligosaccharides. AM symptoms and severity vary among individuals; consequently, AM is often not diagnosed until late childhood. Velmanase alfa (VA), a recombinant human lysosomal alpha-mannosidase product, is the first enzyme replacement therapy indicated to treat non-neurological symptoms of AM in Europe. Previous studies suggested that early VA treatment in children may produce greater clinical benefit over the disease course than starting treatment in adolescents or adults; however, long-term studies in children are limited, and very few studies include children under 6 years of age...
February 27, 2023: Journal of Inherited Metabolic Disease
Maja Risager Nielsen, Christine Jørgensen, Kirsten Ahring, Allan Meldgaard Lund, Mette Cathrine Ørngreen
BACKGROUND: Strict metabolic control with dietary treatment during pregnancy is essential for women with phenylketonuria (PKU), as elevated levels of phenylalanine (Phe) are toxic to the developing fetus. Maternal delay in achievement of the recommended Phe level during pregnancy is associated with delayed development of the child. However, the extent to which risk is changed by later or less stringently performed dietary treatment is unclear. AIM: The aim of this study was to investigate the impact of Phe levels and time of initiation of a Phe-restricted diet in pregnant women with PKU on birth weight, head circumference and later development of their children...
February 26, 2023: Journal of Inherited Metabolic Disease
Silvia Radenkovic, Jon K Laerdahl, Paul H Backe, Eva Morava
No abstract text is available yet for this article.
February 26, 2023: Journal of Inherited Metabolic Disease
Bradley S Miller, Ellen B Fung, Klane K White, Troy C Lund, Paul Harmatz, Paul J Orchard, Chester B Whitley, Lynda E Polgreen
The mucopolysaccharidosis (MPS) disorders have many potential new therapies on the horizon. Thus, historic control data on disease progression and variability are urgently needed. We conducted a 10-year prospective observational study of 55 children with MPS IH (N=23), MPS IA (N=10), non-neuronopathic MPS II (N=13), and MPS VI (N=9) to systematically evaluate bone and joint disease. Annual measurements included height, weight, and goniometry. Mixed effects modeling was used to evaluate changes over time. All participants had been treated with hematopoietic cell transplantation and/or enzyme replacement therapy...
February 25, 2023: Journal of Inherited Metabolic Disease
Marne C Hagemeijer, Jeroen C van den Bosch, Michiel Bongaerts, Edwin H Jacobs, Hannerieke van den Hout, Esmee Oussoren, George J G Ruijter
Oligosaccharidoses, sphingolipidoses and mucolipidoses are lysosomal storage disorders (LSDs) in which defective breakdown of glycan-side chains of glycosylated proteins and glycolipids leads to the accumulation of incompletely degraded oligosaccharides within lysosomes. In metabolic laboratories, these disorders are commonly diagnosed by thin-layer chromatography (TLC) but more recently also mass spectrometry-based approaches have been published. To expand the possibilities to screen for these diseases, we developed an ultra-high-performance liquid chromatography (UHPLC) with high-resolution accurate mass (HRAM) mass spectrometry (MS) screening platform, together with an open-source iterative bioinformatics pipeline...
February 8, 2023: Journal of Inherited Metabolic Disease
An N Dang Do, Irene J Chang, Xutian Jiang, Lynne A Wolfe, Bobby G Ng, Christina Lam, Rhonda E Schnur, Katrina Allis, Hana Hansikova, Nina Ondruskova, Shawn D O'Connor, Amarilis Sanchez-Valle, Arve Vollo, Raymond Y Wang, Zoe Wolfenson, John Perreault, Daniel S Ory, Hudson H Freeze, J Lawrence Merritt, Forbes D Porter
Congenital disorders of glycosylation (CDG) and Niemann-Pick type C (NPC) disease are inborn errors of metabolism that can both present with infantile-onset severe liver disease and other multisystemic manifestations. Plasma bile acid and N-palmitoyl-O-phosphocholineserine (PPCS) are screening biomarkers with proposed improved sensitivity and specificity for NPC. We report an infant with ATP6AP1-CDG who presented with cholestatic liver failure and elevated plasma oxysterols and bile acid, mimicking NPC clinically and biochemically...
January 31, 2023: Journal of Inherited Metabolic Disease
Sangwoo T Han, Ashley Hirt, Elena-Raluca Nicoli, Mari Kono, Camilo Toro, Richard L Proia, Cynthia J Tifft
Treatment of monogenic disorders has historically relied on symptomatic management with limited ability to target primary molecular deficits. However, recent advances in gene therapy and related technologies aim to correct these underlying deficiencies, raising the possibility of disease management or even prevention for diseases that can be treated pre-symptomatically. Tay-Sachs disease (TSD) would be one such candidate, however very little is known about the presymptomatic stage of TSD. To better understand the effects of TSD on brain development, we evaluated the transcriptomes of human fetal brain samples with biallelic pathogenic variants in HEXA...
January 26, 2023: Journal of Inherited Metabolic Disease
Amit Safran, Regina Proskorovski-Ohayon, Marina Eskin-Schwartz, Yuval Yogev, Max Drabkin, Ekaterina Eremenko, Sarit Aharoni, Ofek Freund, Matan M Jean, Nadav Agam, Noam Hadar, Neta Loewenthal, Orna Staretz-Chacham, Ohad S Birk
Hyperinsulinism/hyperammonemia (HI/HA) syndrome has been known to be caused by dominant gain-of-function mutations in GLUD1, encoding the mitochondrial enzyme glutamate dehydrogenase. Pathogenic GLUD1 mutations enhance enzymatic activity by reducing its sensitivity to allosteric inhibition by GTP. Two recent independent studies showed that a similar HI/HA phenotype can be caused by biallelic mutations in SLC25A36, encoding pyrimidine nucleotide carrier 2 (PNC2), a mitochondrial nucleotide carrier that transports pyrimidine and guanine nucleotides across the inner mitochondrial membrane: one study reported a single case caused by a homozygous truncating mutation in SLC25A36 resulting in lack of expression of SLC25A36 in patients' fibroblasts...
January 25, 2023: Journal of Inherited Metabolic Disease
S De Feyter, A Beyens, B Callewaert
In patients with ATP7A-related disorders, counseling is challenging due to clinical overlap between the entities, the absence of predictive biomarkers and a clear genotype-phenotype correlation. We performed a systematic literature review by querying the MEDLINE and Embase databases identifying 143 relevant papers. We recorded data on the phenotype and genotype in 162 individuals with a molecularly confirmed ATP7A-related disorder in order to identify differentiating clinical criteria, evaluate genotype-phenotype correlations and propose management guidelines...
January 24, 2023: Journal of Inherited Metabolic Disease
Thomas J McCorvie, Douglas Ferreira, Wyatt W Yue, D Sean Froese
Vitamin B12 (cobalamin, Cbl) is required as a cofactor by two human enzymes, 5-methyltetrahydrofolate-homocysteine methyltransferase (MTR) and methylmalonyl-CoA mutase (MMUT). Within the body, a vast array of transporters, enzymes and chaperones are required for the generation and delivery of these cofactor forms. How they perform these functions is dictated by the structure and interactions of the proteins involved, the molecular bases of which are only now being elucidated. In this review, we highlight recent insights into human Cbl metabolism and address open questions in the field by employing a protein structure and interactome based perspective...
January 21, 2023: Journal of Inherited Metabolic Disease
Caroline Tuchmann-Durand, Célina Roda, Perrine Renard, Guillaume Mortamet, Claire-Marine Bérat, Lucile Altenburger, Marie Hug de Larauz, Eloise Thevenet, Charles-Henry Cottart, Florence Moulin, Juliette Bouchereau, Anais Brassier, Jean-Baptiste Arnoux, Manuel Schiff, Nathalie Bednarek, Delphine Lamireau, Alexa Garros, Karine Mention, Aline Cano, Lionel Finger, Michele Pelosi, Cécile Sergent Brochet, Laure Caccavelli, Jean-Herlé Raphalen, Sylvain Renolleau, Mehdi Oualha, Pascale de Lonlay
OBJECTIVES: Mutations in the LPIN1 gene constitute a major cause of severe rhabdomyolysis (RM). The TLR9 activation prompted us to treat patients with corticosteroids in acute conditions. METHODS: In patients with LPIN1 mutations, RM and at-risk situations that can trigger RM have been treated in a uniform manner. Since 2015, these patients have also received intravenous corticosteroids. We retrospectively compared data on hospital stays by corticosteroid-treated patients vs...
January 21, 2023: Journal of Inherited Metabolic Disease
Justin Mak, Gang Peng, Anthony Le, Neeru Gandotra, Gregory M Enns, Curt Scharfe, Tina M Cowan
Improved second-tier assays are needed to reduce the number of false positives in newborn screening (NBS) for inherited metabolic disorders including those on the Recommended Uniform Screening Panel (RUSP). We developed an expanded metabolite panel for second-tier testing of dried blood spot (DBS) samples from screen-positive cases reported by the California NBS program, consisting of true- and false-positives from four disorders: glutaric acidemia type I (GA1), methylmalonic acidemia (MMA), ornithine transcarbamylase deficiency (OTCD), and very long-chain acyl-CoA dehydrogenase deficiency (VLCADD)...
January 21, 2023: Journal of Inherited Metabolic Disease
Hana Alharbi, Earnest James Paul Daniel, Jenny Thies, Irene Chang, Dana L Goldner, Bobby G Ng, Peter Witters, Amal Aqul, Frances Velez-Bartolomei, Gregory M Enns, Evelyn Hsu, Elizabeth Kichula, Esther Lee, Charles Lourenco, Sheri A Poskanzer, Sara Rasmussen, Katelyn Saarela, YunZu M Wang, Kimiyo M Raymond, Matthew J Schultz, Hudson H Freeze, Christina Lam, Andrew C Edmondson, Miao He
ATP6AP1-CDG is an X-linked disorder typically characterized by hepatopathy, immunodeficiency and an abnormal type II transferrin glycosylation pattern. Here, we present eleven new patients and clinical updates with biochemical characterization on one previously reported patient. We also document intrafamilial phenotypic variability and atypical presentations, expanding the symptomatology of ATP6AP1-CDG to include dystonia, hepatocellular carcinoma and lysosomal abnormalities on hepatic histology. Three of our subjects received successful liver transplantation...
January 18, 2023: Journal of Inherited Metabolic Disease
Merel A Post, Isis de Wit, Fokje S M Zijlstra, Udo F H Engelke, Arno van Rooij, John Christodoulou, Tiong Yang Tan, Anna Le Fevre, Danqun Jin, Joy Yaplito-Lee, Beom Hee Lee, Karen J Low, Andrew A Mallick, Katrin Õunap, James Pitt, William Reardon, Mari-Anne Vals, Saskia B Wortmann, Hans J C T Wessels, Melissa Bärenfänger, Clara D M van Karnebeek, Dirk J Lefeber
Congenital disorders of glycosylation (CDG) are a clinically and biochemically heterogenous subgroup of inherited metabolic disorders. Most CDG with abnormal N-glycosylation can be detected by transferrin screening, however, MOGS-CDG escapes this routine screening. Combined with the clinical heterogeneity of reported cases, diagnosing MOGS-CDG can be challenging. Here, we clinically characterize ten MOGS-CDG cases, six previously unreported individuals, showing a phenotype characterized by dysmorphic features, global developmental delay, muscular hypotonia, and seizures in all patients and in a minority vision problems and hypogammaglobulinemia...
January 18, 2023: Journal of Inherited Metabolic Disease
A S Nenninger, G Ben-Shlomo, R A Allbaugh, B N Valentine, E Snella, J Jens, N M Ellinwood, J D Smith
Mucopolysaccharidosis type I (MPS I) is a rare lysosomal storage disease caused by α-L-iduronidase enzyme deficiency, resulting in glycosaminoglycan (GAG) accumulation in various cell types, including ocular tissues. Ocular manifestations in humans are common with significant pathological changes including corneal opacification, retinopathy, optic nerve swelling and atrophy, and glaucoma. Available treatments for MPS I are suboptimal and there is limited to no effect in treating the ocular disease. The goal of this study was to characterize the clinical and pathological features of ocular disease in a line of MPS I affected dogs, including changes not previously reported...
January 5, 2023: Journal of Inherited Metabolic Disease
Patrick Forny, Friederike Hörster, Matthias R Baumgartner, Stefan Kölker, Nikolas Boy
Organic acidurias, such as glutaric aciduria type 1, methylmalonic, and propionic aciduria (GA1, MMA, PA) are a prominent group of inherited metabolic diseases involving accumulation of eponymous metabolites causing endogenous intoxication. For all three conditions guidelines for diagnosis and management have been developed and revised over the last years, resulting in three revisions for GA1 and one revision for MMA/PA. The process of clinical guideline development in rare metabolic disorders is challenged by the scarcity and limited quality of evidence available...
January 2, 2023: Journal of Inherited Metabolic Disease
Fetch more papers »
Fetching more papers... Fetching...
Remove bar
Read by QxMD icon Read

Save your favorite articles in one place with a free QxMD account.


Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"

We want to hear from doctors like you!

Take a second to answer a survey question.