Barbara K Burton, Vera Shively, Allegra Quadri, Lauren Warn, Jennifer Burton, Dorothy K Grange, Katherine Christensen, Daniel Groepper, Laura Ashbaugh, Joan Ehrhardt, Khaja Basheeruddin
We describe our experience with population-based newborn screening for mucopolysaccharidosis type II (MPS II) in 586,323 infants by measurement of iduronate-2-sulfatase activity in dried blood spots between December 12, 2017 and April 30, 2022. A total of 76 infants were referred for diagnostic testing, 0.01% of the screened population. Of these, eight cases of MPS II were diagnosed for an incidence of 1 in 73,290. At least four of the eight cases detected had an attenuated phenotype. In addition, cascade testing revealed a diagnosis in four extended family members...
March 6, 2023: Molecular Genetics and Metabolism
Helison Rafael P Carmo, Marcos Y Yoshinaga, Alejandro Rosell Castillo, Adriano Britto Chaves-Filho, Isabella Bonilha, Joaquim Barreto, Stéfanie Primon Muraro, Gabriela Fabiano de Souza, Gustavo Gastão Davanzo, Maurício W Perroud, Kishal Lukhna, Mpiko Ntsekhe, Sean Davidson, Licio A Velloso, Wilson Nadruz, Luiz Sérgio F Carvalho, Miguel Sáinz-Jaspeado, Alessandro S Farias, José Luiz Proença-Módena, Pedro M Moraes-Vieira, Sotirios K Karathanasis, Derek Yellon, Sayuri Miyamoto, Alan T Remaley, Andrei C Sposito
BACKGROUND AND AIMS: Low-density lipoprotein (LDL) plasma concentration decline is a biomarker for acute inflammatory diseases, including coronavirus disease-2019 (COVID-19). Phenotypic changes in LDL during COVID-19 may be equally related to adverse clinical outcomes. METHODS: Individuals hospitalized due to COVID-19 (n = 40) were enrolled. Blood samples were collected on days 0, 2, 4, 6, and 30 (D0, D2, D4, D6, and D30). Oxidized LDL (ox-LDL), and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity were measured...
February 27, 2023: Molecular Genetics and Metabolism
Jakob M Domm, Sarah K Wootton, Jeffrey A Medin, Michael L West
No abstract text is available yet for this article.
February 25, 2023: Molecular Genetics and Metabolism
Parith Wongkittichote, Xinying Hong, Stephen R Master, Shagun Kaur, Sanmati R Cuddapah, Miao He
GA1 (OMIM# 231670) is an organic aciduria caused by defective Glutaryl-CoA dehydrogenase (GCDH), encoded by GCDH. Early detection of GA1 is crucial to prevent patients from developing acute encephalopathic crisis and subsequent neurologic sequelae. Diagnosis of GA1 relies on elevated glutarylcarnitine (C5DC) in plasma acylcarnitine analysis and hyperexcretion of glutaric acid (GA) and 3-hydroxyglutaric acid (3HG) in urine organic acid (UOA) analysis. Low excretors (LE), however, exhibit subtly elevated or even normal plasma C5DC and urinary GA levels, leading to screening and diagnostic challenges...
February 23, 2023: Molecular Genetics and Metabolism
Nichole M Stettner, David J Cutler, Judith L Fridovich-Keil
Classic and clinical variant galactosemia (CG/CVG) are allelic, autosomal recessive disorders that result from deficiency of galactose-1-P uridylyltransferase (GALT). CG/CVG has been reported globally among patients of diverse ancestries, but most large studies of outcomes have included, almost exclusively, patients categorized as White or Caucasian. As a first step to explore whether the cohorts studied are representative of the CG/CVG population at large, we sought to define the racial and ethnic makeup of CG/CVG newborns in a diverse population with essentially universal newborn screening (NBS) for galactosemia: the United States (US)...
February 21, 2023: Molecular Genetics and Metabolism
Deya Alkhatib, Jesus Avila Vega, Issa Pour-Ghaz, Omar Al-Taweel, Sania Khan, Kimberly DeCarr, Anandbir Bath, Aranyak Rawal, David Wilbanks, Joel Raja, Asra Butt, Neeraja Yedlapati, Robert J Hopkin, John L Jefferies
BACKGROUND: Anderson-Fabry disease (AFD) is a rare X-linked lysosomal storage disease due to a genetic variation in the α-galactosidase A (GLA) gene. As a result, the activity of the α-galactosidase A (AGAL-A) enzyme is reduced or absent, which causes sphingolipid deposition within different body parts. AFD typically manifests with cardiovascular, renal, cerebrovascular, and dermatologic involvement. Lymphedema is caused by sphingolipid deposition within lymphatics. Lymphedema can cause intolerable pain and limit daily activities...
February 8, 2023: Molecular Genetics and Metabolism
Vidiyaah Santhanakumaran, Samuel Groeschel, Klaus Harzer, Christiane Kehrer, Saskia Elgün, Stefanie Beck-Wödl, Holger Hengel, Ludger Schöls, Tobias B Haack, Ingeborg Krägeloh-Mann, Lucia Laugwitz
No abstract text is available yet for this article.
February 3, 2023: Molecular Genetics and Metabolism
Denise Salazar, Karen M Kloke, Rubén Bonilla Guerrero, Carlos R Ferreira, Nenad Blau
Inherited metabolic disorders presenting with gastrointestinal (GI) symptoms are characterized by the dysfunction of the esophagus, stomach, small and large intestines, and pancreas. We have summarized associations of signs and symptoms in 339 inherited metabolic diseases presenting with GI symptoms. Feeding difficulties represent the most common abnormality reported for IMDs with GI involvement (37%) followed by intestinal problems (30%), vomiting (22%), stomach and pancreas involvement (8% each), and esophagus involvement (4%)...
February 1, 2023: Molecular Genetics and Metabolism
Sofia Kinton, Michael R Dufault, Mindy Zhang, Kelly George
Pompe disease is a rare lysosomal storage disorder arising from recessive mutations in the acid α-glucosidase gene and resulting in the accumulation of glycogen, particularly in the cardiac and skeletal muscle. The current standard of care is administration of enzyme replacement therapy in the form of alglucosidase alfa or the recently approved avalglucosidase alfa. In order to better understand the underlying cellular processes that are disrupted in Pompe disease, we conducted gene expression analysis on skeletal muscle biopsies obtained from late-onset Pompe disease patients (LOPD) prior to treatment and following six months of enzyme replacement with avalglucosidase alfa...
January 25, 2023: Molecular Genetics and Metabolism
M Judith Peterschmitt, Meredith C Foster, Allena J Ji, Marianne B Zajdel, Gerald F Cox
In Gaucher disease type 1 (GD1), accumulation of the lipid substrates glucosylceramide and glucosylsphingosine (lyso-GL-1 or lyso-Gb1), primarily in the spleen, liver, and bone marrow, leads to progressive hepatosplenomegaly, anemia, thrombocytopenia, and skeletal disease. Plasma glucosylceramide elevations are modest, variable, and normalize within weeks of starting treatment before clinical changes are evident, and therefore, have limited value for monitoring treatment responses. Serum chitotriosidase activity, a widely used GD biomarker, is also elevated in many other conditions but is not measurable in 5-10% of individuals due to a common CHIT1 null variant...
January 25, 2023: Molecular Genetics and Metabolism
B den Hollander, A R J Veenvliet, M Rothuizen-Lindenschot, P van Essen, G Peters, A Santos-Gómez, M Olivella, X Altafaj, M M Brands, B A W Jacobs, C D van Karnebeek
RATIONALE: To date, causal therapy is potentially available for GRIN2B-related neurodevelopmental disorder (NDD) due to loss-of-function (LoF) variants in GRIN2B, resulting in dysfunction of the GluN2B subunit-containing N-methyl-d-aspartate receptor (NMDAR). Recently, in vitro experiments showed that high doses of NMDAR co-agonist d-serine has the potential to boost the activity in GluN2B LoF variant-containing NMDARs. Initial reports of GRIN2B-NDD patients LoF variants, treated with l-serine using different regimens, showed varying effects on motor and cognitive performance, communication, behavior and EEG...
January 21, 2023: Molecular Genetics and Metabolism
James P DeLany, Angela Horgan, Ashley Gregor, Jerry Vockley, Cary O Harding, Melanie B Gillingham
The basis of medical nutrition therapy for patients with LC-FAODs is to provide adequate energy to maintain anabolism and prevent catabolism. In practice, energy needs are estimated based on formulas derived from normal populations but it is unknown if energy expenditure among patients with LC-FAODs is similar to the normal population. We measured resting energy expenditure (REE), total energy expenditure (TEE) and body composition in 31 subjects with LC-FAODs ranging in age from 7 to 64 years. Measured REE was lower than estimated REE by various prediction equations and measured TEE was lower than estimated TEE...
January 18, 2023: Molecular Genetics and Metabolism
Elena-Raluca Nicoli, Mylene Huebecker, Sangwoo T Han, Karolyn Garcia, Jeeva Munasinghe, Martin Lizak, Yvonne Latour, Robin Yoon, Brianna Glase, Michal Tyrlik, Morteza Peiravi, Danielle Springer, Eva H Baker, David Priestman, Rohini Sidhu, Pamela Kell, Xuntian Jiang, Josephine Kolstad, Anna Luisa Kuhn, Mohammed Salman Shazeeb, Maria T Acosta, Richard L Proia, Frances M Platt, Cynthia J Tifft
GM1 gangliosidosis is a rare lysosomal storage disorder affecting multiple organ systems, primarily the central nervous system, and is caused by functional deficiency of β-galactosidase (GLB1). Using CRISPR/Cas9 genome editing, we generated a mouse model to evaluate characteristics of the disease in comparison to GM1 gangliosidosis patients. Our Glb1-/- mice contain small deletions in exons 2 and 6, producing a null allele. Longevity is approximately 50 weeks and studies demonstrated that female Glb1-/- mice die six weeks earlier than male Glb1-/- mice...
January 13, 2023: Molecular Genetics and Metabolism
Parith Wongkittichote, Chanseyha Chhay, Gazelle Zerafati-Jahromi, Judith L Weisenberg, Ali Mian, Laran T Jensen, Dorothy K Grange
Multiple mitochondrial enzymes employ lipoic acid as a coenzyme. Pathogenic variants in LIAS, encoding lipoic acid synthase (LIAS), are associated with autosomal recessive LIAS-related disorder (OMIM# 614462). This disorder is characterized by infantile-onset hypotonia, profound psychomotor delay, epileptic encephalopathy, nonketotic hyperglycinemia, and lactic acidosis. We present the case of a 20-year-old female who experienced developmental deficits at the age of 6 months and began to have seizures at 3 years of age...
January 7, 2023: Molecular Genetics and Metabolism
Chenghao Zhang, Rahul Gawri, Yian Khai Lau, Lynn A Spruce, Hossein Fazelinia, Zhirui Jiang, Stephanie Y Jo, Carla R Scanzello, Wilfried Mai, George R Dodge, Margret L Casal, Lachlan J Smith
Mucopolysaccharidosis I is a lysosomal storage disorder characterized by deficient alpha-L-iduronidase activity, leading to abnormal accumulation of glycosaminoglycans in cells and tissues. Synovial joint disease is prevalent and significantly reduces patient quality of life. There is a critical need for improved understanding of joint disease pathophysiology in MPS I, including specific biomarkers to predict and monitor joint disease progression, and response to treatment. The objective of this study was to leverage the naturally-occurring MPS I canine model and undertake an unbiased proteomic screen to identify systemic biomarkers predictive of local joint disease in MPS I...
January 4, 2023: Molecular Genetics and Metabolism
Kenzie Melvill, Jennifer Fitzpatrick, David S Rosenblatt
No abstract text is available yet for this article.
December 28, 2022: Molecular Genetics and Metabolism
Ylenia Vaia, Eleonora Mura, Davide Tonduti
BACKGROUND AND OBJECTIVES: Alexander disease (AxD) is a rare progressive leukodystrophy caused by autosomal dominant mutations in the Glial Fibrillary Acidic Protein (GFAP) gene. Three main disease classifications are currently in use, the traditional one defined by the age of onset, and two other based on clinical features at onset and brain MRI findings. Recently, we proposed a new classification, which is based on taking into consideration not only the presenting features, but also data related to the clinical course...
March 2023: Molecular Genetics and Metabolism
Rebecca L Koch, Claudia Soler-Alfonso, Bridget T Kiely, Akihiro Asai, Ariana L Smith, Deeksha S Bali, Peter B Kang, Andrew P Landstrom, H Orhan Akman, T Andrew Burrow, Jennifer L Orthmann-Murphy, Deberah S Goldman, Surekha Pendyal, Areeg H El-Gharbawy, Stephanie L Austin, Laura E Case, Raphael Schiffmann, Michio Hirano, Priya S Kishnani
Glycogen storage disease type IV (GSD IV) is an ultra-rare autosomal recessive disorder caused by pathogenic variants in GBE1 which results in reduced or deficient glycogen branching enzyme activity. Consequently, glycogen synthesis is impaired and leads to accumulation of poorly branched glycogen known as polyglucosan. GSD IV is characterized by a remarkable degree of phenotypic heterogeneity with presentations in utero, during infancy, early childhood, adolescence, or middle to late adulthood. The clinical continuum encompasses hepatic, cardiac, muscular, and neurologic manifestations that range in severity...
March 2023: Molecular Genetics and Metabolism
Lennart Moritz, Katharina Klotz, Sarah Catharina Grünert, Luciana Hannibal, Ute Spiekerkoetter
Phenylketonuria (PKU, MIM #261600) is one of the most common inborn errors of metabolism (IEM) with an incidence of 1:10000 in the European population. PKU is caused by autosomal recessive mutations in phenylalanine hydroxylase (PAH) and manifests with elevation of phenylalanine (Phe) in plasma and urine. Untreated PKU manifests with intellectual disability including seizures, microcephaly and behavioral abnormalities. Early treatment and good compliance result in a normal intellectual outcome in many but not in all patients...
March 2023: Molecular Genetics and Metabolism
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No abstract text is available yet for this article.
February 2023: Molecular Genetics and Metabolism
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