Stephen J Staklinski, Mario C Chang, Rebecca C Ahrens-Nicklas, Shagun Kaur, Arianna K Stefanatos, Elizabeth E Dudenhausen, Matthew E Merritt, Michael S Kilberg
Asparagine synthetase (ASNS) catalyzes the synthesis of asparagine (Asn) from aspartate and glutamine. Biallelic mutations in the ASNS gene result in ASNS Deficiency (ASNSD). Children with ASNSD exhibit congenital microcephaly, epileptic-like seizures, and continued brain atrophy, often leading to premature mortality. This report describes a 4-year-old male with global developmental delay and seizures with two novel mutations in the ASNS gene, c.614A > C (maternal) and c.1192dupT (paternal) encoding p...
March 2023: JIMD Reports
Stefanie Witt, Kaja Kristensen, Katharina Hohenfellner, Julia Quitmann
Nephropathic cystinosis is a rare autosomal recessive lysosomal storage disorder. With the availability of treatment and renal replacement therapy, nephropathic cystinosis has evolved from an early fatal disease to a chronic, progressive disorder with potentially high impairment. We aim to review the literature on the health-related quality of life and identify appropriate patient-reported outcome measurements to assess the health-related quality of life of patients with cystinosis. For this review, we conducted a literature search in PubMed and Web of Science in September 2021...
March 2023: JIMD Reports
Alfonso Galderisi, Elsa Kermorvant-Duchemin, Alejandra Daruich, Adeline Alice Bonnard, Alexandre Lapillonne, Marie-Stéphanie Aubelle, Bruna Perrella, Yoann Vial, Héléne Cave, Marianne Berdugo, Pierre-Henri Jarreau, Michel Polak, Jacques Beltrand
Early treatment of neonatal diabetes with sulfonylureas has been proven to produce marked improvements of neurodevelopment, beside the demonstrated efficacy on glycemic control. Several barriers still prevent an early treatment in preterm babies including the limited availability of suitable galenic form of glibenclamide. We adopted oral glibenclamide suspension (Amglidia) for the early treatment of neonatal diabetes due to an homozygous variant of KCNJ11 gene c.10C>T [p.Arg4Cys] in an extremely preterm infant born at 26 + 2 weeks' of gestational age...
March 2023: JIMD Reports
Ruqaiah Altassan, Dimpna C Albert-Brotons, Mohammad Alowain, Zohair Al-Halees, Jaak Jaeken, Eva Morava
We report successful heart transplantation in a phosphoglucomutase 1 deficient (PGM1-CDG) patient. She presented with facial dysmorphism, bifid uvula and structural heart defects. Newborn screening was positive for classic galactosemia. The patient was on a galactose-free diet for 8 months. Eventually, whole exome sequencing excluded the galactosemia and revealed PGM1-CDG. Oral D-galactose therapy was started. Rapid deterioration of the progressive dilated cardiomyopathy prompted heart transplantation at the age of 12 months...
March 2023: JIMD Reports
Margot Eyskens, Luc Bruyndonckx, André B P Van Kuilenburg, François Eyskens
We report a unique case of an infant with a severe dilated cardiomyopathy as the clinical presentation of sialidosis type II (OMIM 256550), a rare autosomal recessive inherited lysosomal storage disease that is characterized by partial or complete deficiency of α-neuraminidase, following mutations in the gene neuraminidase 1 ( NEU1 ), located on the short arm of chromosome 6 (6p21.3). Accumulation of metabolic intermediates leads to severe morbidity, especially myoclonus, gait disturbances, cherry-red macules with secondary loss of visual acuity, impaired color vision and night blindness, and sometimes additional neurological findings such as seizures...
March 2023: JIMD Reports
Natasha Rudy, Kazuhiro Aoki, Amitha Ananth, Lynda Holloway, Cindy Skinner, Anna Hurst, Michael Tiemeyer, Richard Steet
GM3 synthase deficiency (GM3SD) is caused by biallelic variants in ST3GAL5 . The ganglioside GM3, enriched in neuronal tissues, is a component of lipid rafts and regulates numerous signaling pathways. Affected individuals with GM3SD exhibit global developmental delay, progressive microcephaly, and dyskinetic movements. Hearing loss and altered skin pigmentation are also common. Most of the reported variants in ST3GAL5 are found in motifs conserved across all sialyltransferases within the GT29 family of enzymes...
March 2023: JIMD Reports
Augusto Monteiro Magalhães, Ana Filipa Moleiro, Esmeralda Rodrigues, Sérgio Castro, José Fonseca, Elisa Leão-Teles
Mucopolysaccharidosis (MPS) VI is a rare genetic disease characterized by deficient activity of N-acetylgalactosamine 4-sulfatase, leading to the systemic deposition of glycosaminoglycans. Ocular involvement is classically characterized by progressive corneal clouding, ocular hypertension (OHT), and optic neuropathy. Although corneal clouding can be solved with penetrating keratoplasty (PK), visual impairment usually remains, being frequently attributed to glaucoma. The purpose of this study was to retrospectively describe a series of MPS VI patients with optic neuropathy in order to deepen the knowledge regarding the causes of severe visual impairment among these patients...
March 2023: JIMD Reports
Line Gutte Borgwardt, Ferdinando Ceravolo, Giulia Zardi, Andrea Ballabeni, Allan Meldgaard Lund
Alpha-mannosidosis (AM), an autosomal recessive disorder caused by pathogenic biallelic variants in the MAN2B1 gene, leads to lysosomal alpha-mannosidase deficiency and accumulation of mannose-rich oligosaccharides. Velmanase alfa (VA), a recombinant human lysosomal alpha-mannosidase, is the first enzyme replacement therapy for non-neurological symptoms of AM. Previously, a potential relationship was identified between three MAN2B1 genotype/subcellular localization subgroups (G1, G2, and G3) and AM disease severity...
March 2023: JIMD Reports
Isaac Bernhardt, Emma Glamuzina, Bryony Ryder, Detlef Knoll, Natasha Heather, Mark De Hora, Dianne Webster, Callum Wilson
Newborn screening (NBS) for classical galactosaemia (CG) facilitates early diagnosis and treatment to prevent life-threatening complications, but remains controversial, and screening protocols vary widely between programmes. False-negatives associated with first-tier screening of total galactose metabolites (TGAL) are infrequently reported; however, newborns with TGAL below the screening threshold have not been systematically studied. Following the diagnosis of CG in two siblings missed by NBS, a retrospective cohort study of infants with TGAL just below the cut-off (1...
March 2023: JIMD Reports
Caoimhe Howard, Arundhati Dev-Borman, John Stokes, Declan O'Rourke, Ciara Gillespie, Eilish Twomey, Ina Knerr, Ritma Boruah
Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation in mitochondria. Pathogenic variants in MTFMT have been described in association with clinical presentations with Leigh syndrome, as well with as multisystem involvement (particularly cardiac and ocular involvement). There is a spectrum of severity, but many reported presentations have been milder with a better prognosis than other pathogenic variants associated with Leigh syndrome. We describe the case of a 9-year-old boy homozygous for a pathogenic MTFMT variant (c...
March 2023: JIMD Reports
Christopher D Ma, Denise Faust, Herbert L Bonkovsky
A 47-year-old woman with acute intermittent porphyria (AIP) has had recurring symptoms after achieving biochemical normalization of her urinary 5-aminolevulinic acid (ALA), porphobilinogen (PBG), and total porphyrins with givosiran. She has had normal liver tests, mildly decreased renal function, and sustained normal urinary ALA, PBG, and porphyrins with no rebound in her laboratory test results throughout treatment. She continues to tolerate monthly givosiran injections with no adverse effects, but she still experiences what she believes are acute porphyric attacks every 1-2 months...
March 2023: JIMD Reports
Milad Khedr, Nick Sireau, George Bou-Gharios, Jim A Gallagher, Lakshminarayan R Ranganath
No abstract text is available yet for this article.
March 2023: JIMD Reports
Jordi To-Figueras, Esther Titos, Paula Aguilera, Alba Díaz, Javier Muñoz-Luque, Irene Madrigal, Celia Badenas, Mercè Torra, Constantino Fondevila, Jordi Colmenero
Acute intermittent porphyria (AIP) is a rare disease caused by a deficiency of hydroxymethylbilane synthase (HMBS), the third enzyme of the heme-synthesis pathway. Decreased enzymatic activity in the liver induces an overproduction of heme-precursors and acute neurological attacks. We report a 36-years-old female with AIP with a long-term history of severe, disabling, recurrent attacks, who underwent curative liver transplantation. Tissue samples from the explant were obtained for transcriptome analysis. Whole RNA was extracted and 16 gene-transcripts were selected and investigated by quantitative polymerase chain reaction...
January 2023: JIMD Reports
Lebreton Louis, Gaschignard Margaux, Guibet Claire, Lamireau Delphine, Roche Sandrine, Richard Emmanuel, Ged Cécile, Mesli Samir, Redonnet-Vernhet Isabelle
Primary carnitine deficiency (PCD) is an inherited disease of fatty acid beta-oxidation with autosomal recessive inheritance. The disease manifests as metabolic decompensation with hypoketotic hypoglycaemia associated with cardiomyopathy, hepatomegaly, rhabdomyolysis, and seizures. Various outcomes are described from asymptomatic adults to dramatic sudden infant death syndrome cases. We present a severe case of PCD decompensation in an 18-week-old female. She presented with hypotonia, moaning, diarrhea, and vomiting at the pediatric emergency...
January 2023: JIMD Reports
Zhi-Jie Xia, Bobby G Ng, Elizabeth Jennions, Maria Blomqvist, Anneli Sandqvist Wiklund, Carola Hedberg-Oldfors, Carlos Rodriguez Gonzalez, Hudson H Freeze, Sofia Ygberg, Erik A Eklund
Here, we present the first two Swedish cases of Conserved Oligomeric Golgi complex subunit 6-congenital disorders of glycosylation (COG6-CDG). Their clinical symptoms include intellectual disability, Attention Deficit/Hyperactivity Disorder (ADHD), delayed brain myelinization, progressive microcephaly, joint laxity, hyperkeratosis, frequent infections, and enamel hypoplasia. In one family, compound heterozygous variants in COG6 were identified, where one (c.785A>G; p.Tyr262Cys) has previously been described in patients of Moroccan descent, whereas the other (c...
January 2023: JIMD Reports
Loek L Crefcoeur, M Rebecca Heiner-Fokkema, Rose E Maase, Gepke Visser, Monique G M de Sain-van der Velden
In the Netherlands, newborns are referred by the newborn screening (NBS) Program when a low free carnitine (C0) concentration (<5 μmol/l) is detected in their NBS dried blood spot. This leads to ~85% false positive referrals who all need an invasive, expensive and lengthy evaluation. We investigated whether a ratio of urine C0 / plasma C0 (RatioU:P ) can improve the follow-up protocol for primary carnitine deficiency (PCD). A retrospective study was performed in all Dutch metabolic centres, using samples from newborns and mothers referred by NBS due to low C0 concentration...
January 2023: JIMD Reports
Johannes Nadler, Maren Hermanns-Clausen, Karin Dilger
Eliglustat is an orphan medicine used for long-term treatment of Gaucher disease type 1 (GD1) in adults. GD1 is a genetic condition, in which glucosylceramide builds up in the body, typically in liver, spleen, and bone. Clinical signs and symptoms of the disease are anemia, tiredness, easy bruising, hepatosplenomegaly, bone pain, and fractures. Eliglustat works by blocking glucosylceramide synthase (substrate reduction therapy). This medicine is subject to additional safety monitoring by regulatory authorities in the European Union...
January 2023: JIMD Reports
Katsuyuki Yokoi, Yoko Nakajima, Yoshihisa Takahashi, Takashi Hamajima, Go Tajima, Kazuyoshi Saito, Shunsuke Miyai, Hidehito Inagaki, Tetsushi Yoshikawa, Hiroki Kurahashi, Tetsuya Ito
Mutations in transport and Golgi organization 2 homolog ( TANGO2 ) have recently been described as a cause of an autosomal recessive syndrome characterized by episodes of metabolic crisis associated with rhabdomyolysis, cardiac arrhythmias, and neurodegeneration. Herein, we report a case of a one-and-a-half-year-old Japanese girl, born to nonconsanguineous parents, who presented with metabolic crisis characterized by hypoglycemia with hypoketonemia, rhabdomyolysis, lactic acidosis, and prolonged corrected QT interval (QTc) at the age of 6 months...
January 2023: JIMD Reports
Pilar Giraldo, Marcio Andrade-Campos, Montserrat Morales
Management of Gaucher disease (GD) is challenging due to its wide genotypic and phenotypic variability and changing clinical manifestations due to effective treatment. Sixteen face-to-face meetings with experts were held in order to discuss daily clinical practice and identify controversies regarding the management of GD. With this information, a questionnaire with 93 recommendations for different clinical scenarios was designed, and a Delphi survey among 86 physicians with experience in GD was conducted. Consensus was reached on 73 out of the 93 items...
January 2023: JIMD Reports
Amy Dickey, Kristen Wheeden, Desiree Lyon, Sue Burrell, Sean Hegarty, Rocco Falchetto, Edrin R Williams, Jasmin Barman-Aksözen, Marc DeCongelio, Alison Bulkley, Joana E Matos, Tarek Mnif, Jordanna Mora, John J Ko, Stephen Meninger, Stephen Lombardelli, Danielle Nance
Acute hepatic porphyria (AHP) is a group of rare genetic diseases of heme biosynthesis resulting in severe neurovisceral attacks and chronic complications that negatively impact patients' well-being. This study evaluated the impacts of AHP on patients' physical and emotional health from a global perspective. Adult patients from the United States, Italy, Spain, Australia, Mexico, and Brazil with AHP with >1 porphyria attack within the past 2 years or receiving intravenous hemin and/or glucose for attack prevention completed an online survey assessing demographics, health characteristics, and patient-reported outcomes...
January 2023: JIMD Reports
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