1,431 results match your criteria Lesch-Nyhan Syndrome


HGprt deficiency disrupts dopaminergic circuit development in a genetic mouse model of Lesch-Nyhan disease.

Cell Mol Life Sci 2022 Jun 4;79(6):341. Epub 2022 Jun 4.

Department of Molecular Animal Physiology, Donders Center for Neuroscience, Radboud University Nijmegen, Nijmegen, The Netherlands.

In Lesch-Nyhan disease (LND), deficiency of the purine salvage enzyme hypoxanthine guanine phosphoribosyl transferase (HGprt) leads to a characteristic neurobehavioral phenotype dominated by dystonia, cognitive deficits and incapacitating self-injurious behavior. It has been known for decades that LND is associated with dysfunction of midbrain dopamine neurons, without overt structural brain abnormalities. Emerging post mortem and in vitro evidence supports the hypothesis that the dopaminergic dysfunction in LND is of developmental origin, but specific pathogenic mechanisms have not been revealed. Read More

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Architecture of a multi-channel and easy-to-make microfluidic paper-based colorimetric device (μPCD) towards selective and sensitive recognition of uric acid by AuNPs: an innovative portable tool for the rapid and low-cost identification of clinically relevant biomolecules.

RSC Adv 2021 Aug 10;11(44):27298-27308. Epub 2021 Aug 10.

Jiangsu Co-Innovation Center for Efficient Processing and Utilization of Forest Resources, International Innovation Center for Forest Chemicals and Materials, Nanjing Forestry University Nanjing 210037 China

Uric acid (UA) is the end product of purine metabolism. Uric acid is usually excreted in the urine, but its abnormal increase and toxic amount can lead to diseases such as gout, hyperuricemia, Lesch-Nyhan syndrome, and cardiovascular disease. On the other hand, UA reduction can lead to neurodegenerative diseases such as sarcoma, glioblastoma, Hodgkin, and Therefore, rapid identification of UA is of great importance. Read More

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Liquid crystal-based sensitive and selective detection of uric acid and uricase in body fluids.

Talanta 2022 Jul 4;244:123455. Epub 2022 Apr 4.

Qilu University of Technology (Shandong Academy of Sciences), Shandong Analysis and Test Center, Jinan, 250014, China; School of Pharmaceutical Sciences, Qilu University of Technology (Shandong Academy of Sciences), Jinan, 250014, China.

The abnormal levels of uric acid (UA) in body fluids are associated with gout, type (II) diabetes, leukemia, Lesch-Nyhan syndrome, uremia, kidney damage, and cardiovascular diseases. Also, the presence of uricase (UOx) symbolizes genetic disorders and corresponding complications. Therefore, the detection of UA and UOx in the body fluids is significant for clinical diagnosis. Read More

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PUS7 deficiency in human patients causes profound neurodevelopmental phenotype by dysregulating protein translation.

Mol Genet Metab 2022 03 1;135(3):221-229. Epub 2022 Feb 1.

Medical Genetics Branch, National Human Genome Research Institute, Bethesda, MD 20892, United States of America; Undiagnosed Diseases Program, Office of the Director, National Institutes of Health, Bethesda, MD 20892, United States of America.

Protein translation is a highly regulated process involving the interaction of numerous genes on every component of the protein translation machinery. Upregulated protein translation is a hallmark of cancer and is implicated in autism spectrum disorder, but the risks of developing each disease do not appear to be correlated with one another. In this study we identified two siblings from the NIH Undiagnosed Diseases Program with loss of function variants in PUS7, a gene previously implicated in the regulation of total protein translation. Read More

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Congenital anomalies-associated Riga-Fede disease as an early manifestation of Lesch-Nyhan syndrome: rare entities in the same pediatric patient-a case report.

BMC Oral Health 2022 02 2;22(1):26. Epub 2022 Feb 2.

Faculty of Dentistry, Oral Medicine, Periodontology, Diagnosis and Radiology Department, Alexandria University, Alexandria, Egypt.

Background: Riga-Fede disease is a rare begnin disorder of the oral tissues, it can be associated with congenital anomalies and neurological disturbances. Lesch-Nyhan syndrome is a rare X-linked recessive disorder characterized by neurological and behavioral manifestations. A patient can rarely be diagnosed with both diseases in a lifetime. Read More

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February 2022

Safety and Efficacy of Botulinum Toxin in the Treatment of Self-Biting Behavior in Lesch-Nyhan Disease.

Pediatr Neurol 2022 02 1;127:6-10. Epub 2021 Nov 1.

Department of Pediatric Neurology, Hospital Universitario La Paz, Madrid, Spain; Department of Pediatrics, Universidad Autonoma de Madrid, Madrid, Spain.

Background: Lesch-Nyhan disease (LND) is a disease of purine metabolism linked to chromosome X due to the absence or near-absence of enzyme hypoxanthine-guanine phosphoribosyltransferase. Patients with LND have a compulsive autoaggressive behavior that consists of self-mutilation by biting.

Methods: The objective of this study was to explore the safety and efficacy of botulinum toxin (BoNT) injected into the masticatory muscles and biceps brachii to reduce self-mutilation in patients with LND. Read More

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February 2022

Potential molecular link between the β-amyloid precursor protein (APP) and hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme in Lesch-Nyhan disease and cancer.

Authors:
Khue Vu Nguyen

AIMS Neurosci 2021 28;8(4):548-557. Epub 2021 Oct 28.

Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego, Building CTF, Room C-103, 214 Dickinson Street, San Diego, CA 92103-8467, USA.

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorders of purine metabolic in which the cytoplasmic enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 60 years ago, however, up to now, there is no satisfactory explanation of how deficits in enzyme HGprt can lead to LND with the development of the persistent and severe self-injurious behavior. Recently, a role for epistasis between the mutated hypoxanthine phosphoribosyltransferase 1 () and the β-amyloid precursor protein (APP) genes affecting the regulation of alternative APP pre-mRNA splicing in LND has been demonstrated. Read More

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October 2021

Paroxysmal hyperthermia, dysautonomia and rhabdomyolysis in a patient with Lesch-Nyhan syndrome.

JIMD Rep 2021 Nov 28;62(1):30-34. Epub 2021 Sep 28.

Department of Pediatrics, Division of Pediatric Neurology Boston University School of Medicine, Boston Medical Center Boston Massachusetts USA.

Lesch-Nyhan syndrome is an x-linked genetic disorder of purine metabolism that results in the overproduction of uric acid and neurologic deficits manifesting as intellectual disability, dystonia, other movement disorders and self-mutilation. We describe a 12-year-old patient with a history of Lesch-Nyhan syndrome, G6PD deficiency and central diabetes insipidus and multiple admissions for fever, acute kidney injury and transaminitis in the setting of rhabdomyolysis. The patient's temperature dysregulation and dysautonomia is likely attributable to abnormal neurotransmitter release, particularly that of dopamine, in the central nervous system. Read More

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November 2021

Microstructural white matter abnormalities in Lesch-Nyhan disease.

Eur J Neurosci 2022 01 6;55(1):264-276. Epub 2021 Dec 6.

Department of Psychiatry and Behavioral Sciences, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Lesch-Nyhan disease is a rare, sex-linked, genetic neurodevelopmental disorder that is characterized by hyperuricemia, dystonia, cognitive impairment and recurrent self-injury. We previously found reduced brain white matter volume in patients with Lesch-Nyhan disease compared with healthy adults using voxel-based morphometry. Here, we address the structural integrity of white matter via diffusion tensor imaging. Read More

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January 2022

50 Years Ago in TheJournalofPediatrics: Diagnosis of Self-Mutilation and Hyperuricemia.

J Pediatr 2021 Oct;237:86

Department of Pediatric Research, University of Oslo, Oslo, Norway; Ann and Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine, Chicago, Illinois.

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October 2021

Cerebral Venous Sinus Thrombosis in a Child with Lesch-Nyhan Syndrome.

Neurol India 2021 Jul-Aug;69(4):1021-1023

Child Neurology Division, Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.

Lesch-Nyhan syndrome is a rare neurometabolic condition characterized by progressive choreoathetosis, intellectual disability, and peculiar manifestations like self-mutilation. Occasional case reports in adults have suggested an association between Lesch-Nyhan syndrome and hypercoagulability; however, no such report of either a venous or arterial stroke in children with Lesch-Nyhan Syndrome exists in literature. We present a 3-year-old boy with global developmental delay, dystonic posturing, choreoathetoid movements, and self-mutilation involving fingers and lips. Read More

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September 2021

Selecting for and Checking Cells with HGPRT Deficiency for Hybridoma Production.

Cold Spring Harb Protoc 2021 09 1;2021(9). Epub 2021 Sep 1.

For drug-selective media to work for hybridoma selection, myeloma cells expressing a mutation abrogating the function of their HGPRT gene (and subsequently unable to produce purines for DNA biosynthesis) are used. HGPRT will recognize 8-AG as a substrate and convert it to the monophosphate nucleotide. The 8-AG-containing nucleotide is then processed further and incorporated into DNA and RNA, where it is toxic. Read More

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September 2021

Lesch-Nyhan disease causes impaired energy metabolism and reduced developmental potential in midbrain dopaminergic cells.

Stem Cell Reports 2021 07 1;16(7):1749-1762. Epub 2021 Jul 1.

Psychiatric Genetics Group, McGill University, Montreal, QC, Canada; Department of Psychiatry, McGill University and Douglas Hospital Research Institute, 6875 LaSalle Boulevard, Frank Common Building, Room 2101.2, Montreal, QC H4H 1R3, Canada. Electronic address:

Mutations in HPRT1, a gene encoding a rate-limiting enzyme for purine salvage, cause Lesch-Nyhan disease which is characterized by self-injury and motor impairments. We leveraged stem cell and genetic engineering technologies to model the disease in isogenic and patient-derived forebrain and midbrain cell types. Dopaminergic progenitor cells deficient in HPRT showed decreased intensity of all developmental cell-fate markers measured. Read More

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Living with Lesch-Nyhan disease

Rev Prat 2021 03;71(3):291-292

Administratrice de l'Association Lesch-Nyhan Action (LNA).

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Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

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Lesch-Nyhan syndrome due to a splice-site mutation in a 14-month-old boy presenting as acute renal failure.

Clin Nephrol 2021 Aug;96(2):120-123

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited disorder caused by mutations in gene resulting in deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). LND is characterized by hyperuricemia and a spectrum of neurological and behavioral manifestations. We describe a rare case of a 14-month-old boy presenting with acute renal failure and hyperuricemia. Read More

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Problems associated with antiviral drugs and vaccines development for COVID-19: approach to intervention using expression vectors via GPI anchor.

Authors:
Khue Vu Nguyen

Nucleosides Nucleotides Nucleic Acids 2021 13;40(6):665-706. Epub 2021 May 13.

Department of Medicine, Biochemical Genetics and Metabolism, The Mitochondrial and Metabolic Disease Center, School of Medicine, University of California, San Diego, San Diego, CA, USA.

The outbreak of a novel coronavirus responsible for the severe acquired respiratory syndrome: SARS-CoV-2, also known as coronavirus disease 2019: COVID-19, represents a pandemic threat that has been declared a public health emergency of international concern. The CoV spike (S) glycoprotein is a key target for diagnostic, development of antibodies, entry inhibitors, and vaccines. COVID-19 also recognizes angiotensin-converting enzyme 2 (ACE2) as its host receptor binding to viral S protein. Read More

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Induced pluripotent stem cells from subjects with Lesch-Nyhan disease.

Sci Rep 2021 04 19;11(1):8523. Epub 2021 Apr 19.

Department of Neurology, Emory University School of Medicine, 101 Woodruff Circle, 6305 Woodruff Memorial Building, Atlanta, GA, 30322, USA.

Lesch-Nyhan disease (LND) is an inherited disorder caused by pathogenic variants in the HPRT1 gene, which encodes the purine recycling enzyme hypoxanthine-guanine phosphoribosyltransferase (HGprt). We generated 6 induced pluripotent stem cell (iPSC) lines from 3 individuals with LND, along with 6 control lines from 3 normal individuals. All 12 lines had the characteristics of pluripotent stem cells, as assessed by immunostaining for pluripotency markers, expression of pluripotency genes, and differentiation into the 3 primary germ cell layers. Read More

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Reduction of self-mutilating behavior and improved oromotor function in a patient with Lesch-Nyhan syndrome following botulinum toxin injection: A case report.

J Pediatr Rehabil Med 2021 ;14(1):133-136

Rutgers New Jersey Medical School, Department of Physical Medicine and Rehabilitation, Newark, NJ, USA.

Lesch-Nyhan syndrome is a genetic metabolic disorder often involving dystonia and self-mutilating behavior. This case report describes a 13-year-old boy with Lesch-Nyhan syndrome and self-mutilating behavior who received botulinum toxin injections to his bilateral masseter muscles after failing multiple other treatments. Following injections, the patient had reduction in self-biting, along with improvements in speech, mastication and feeding observed in speech therapy. Read More

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October 2021

Deep brain stimulation in Lesch-Nyhan disease: outcomes from the patient's perspective.

Dev Med Child Neurol 2021 08 10;63(8):963-968. Epub 2021 Mar 10.

Departments of Neurology and Human Genetics, Emory University School of Medicine, Atlanta.

Aim: To provide insight into outcome and long-term safety and efficacy of deep brain stimulation (DBS), from the perspective of individuals with Lesch-Nyhan disease (LND) and their families.

Method: We used patient-centered outcome measures to assess long-term outcomes of DBS for 14 individuals (mean [SD] age 10y 10mo [5y 6mo], range 5-23y, all males) with LND, after an average duration of 5y 6mo (range 11mo-10y 5mo) after surgery. We compared these results with a comprehensive review of previously published cases. Read More

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Recurrent Xanthine Stones in a Young Patient with Lesch-Nyhan Syndrome.

J Endourol Case Rep 2020 29;6(4):268-270. Epub 2020 Dec 29.

Department of Urology, Comprehensive Kidney Stone Center, UC San Diego Health, San Diego, California, USA.

Lesch-Nyhan syndrome results from a rare X-linked inborn error of metabolism leading to a total body accumulation of uric acid. Clinical manifestations include self-mutilating behavior, poor muscle control, intellectual disability, gout, and kidney disease. Unfortunately, life expectancy is limited to the second or third decade of life because of symptoms associated with hyperuricemia, particularly renal failure. Read More

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December 2020

Oxidopamine and oxidative stress: Recent advances in experimental physiology and pharmacology.

Chem Biol Interact 2021 Feb 13;336:109380. Epub 2021 Jan 13.

Ben-Gurion University of the Negev, Zlotowski Center for Neuroscience, Faculty of Health Sciences, Department of Physiology and Cell Biology, P.O.B. 653, Beersheba, Israel.

Oxidopamine (6-hydroxydopamine, 6-OHDA) is a toxin commonly used for the creation of experimental animal models of Parkinson's disease, attention-deficit hyperactivity disorder, and Lesch-Nyhan syndrome. Its exact mechanism of action is not completely understood, although there are many indications that it is related to the generation of reactive oxygen species (ROS), primarily in dopaminergic neurons. In certain experimental conditions, oxidopamine may also cause programmed cell death via various signaling pathways. Read More

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February 2021

Clinical and molecular findings in a Turkish family with an ultra-rare condition, ELP2-related neurodevelopmental disorder.

Mol Biol Rep 2021 Jan 3;48(1):701-708. Epub 2021 Jan 3.

Department of Pediatrics, Faculty of Medicine, Duzce University, Duzce, Turkey.

Elongator is a multi-subunit protein complex bearing six different protein subunits, Elp1 to -6, that are highly conserved among eukaryotes. Elp2 is the second major subunit of Elongator and, together with Elp1 and Elp3, form the catalytic core of this essential complex. Pathogenic variants that affect the structure and function of the Elongator complex may cause neurodevelopmental disorders. Read More

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January 2021

CT, US and MRI of xanthine urinary stones: in-vitro and in-vivo analyses.

BMC Urol 2020 Oct 12;20(1):157. Epub 2020 Oct 12.

Division of Pediatric Radiology, Department of Radiology, Montefiore Medical Center, Albert Einstein College of Medicine, 111 East, 210th Street, Bronx, NY, 10467, USA.

Background: Xanthine urinary stones are a rare entity that may occur in patients with Lesch-Nyhan syndrome receiving allopurinol. There is little literature describing imaging characteristics of these stones, and the most appropriate approach to imaging these stones is therefore unclear. We performed in-vitro and in-vivo analyses of xanthine stones using computed tomography (CT) at different energy levels, ultrasound (US), and magnetic resonance imaging (MRI). Read More

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October 2020

Atypical Cadherin FAT3 Is a Novel Mediator for Morphological Changes of Microglia.

eNeuro 2020 Nov/Dec;7(6). Epub 2020 Dec 16.

Faculty of Life and Environmental Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8577, Japan

Microglia are resident macrophages that are critical for brain development and homeostasis. Microglial morphology is dynamically changed during postnatal stages, leading to regulating synaptogenesis and synapse pruning. Moreover, it has been well known that the shape of microglia is also altered in response to the detritus of the apoptotic cells and pathogens such as bacteria and viruses. Read More

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Hypoxanthine phosphoribosyltransferase (HPRT)-deficiency is associated with impaired fertility in the female rat.

Mol Reprod Dev 2020 09 27;87(9):930-933. Epub 2020 Aug 27.

The Roslin Institute and R(D)VS, University of Edinburgh, Edinburgh, UK.

The purine hypoxanthine plays important role in regulating oocyte maturation and early embryonic development. The enzyme hypoxanthine phosphoribosyltransferase (HPRT) recycles hypoxanthine to generate substrates for nucleotide synthesis and key metabolites, and here we show that HPRT deficiency in the rat disrupts early embryonic development and causes infertility in females. Read More

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September 2020

Delayed emergence from propofol anesthesia in a patient with Lesch-Nyhan syndrome: A case report.

Medicine (Baltimore) 2020 Aug;99(34):e21847

Department of Anesthesiology and Pain Medicine, Yeungnam University School of Medicine, Daegu, Republic of Korea.

Rationale: Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder presenting with uric acid overproduction, neurocognitive disability, and behavioral disturbances. Inhalational anesthesia has been frequently used in LNS patients undergoing surgery. Characteristic compulsive self-injurious behavior and high risk of emesis may hinder inhalational induction. Read More

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An electrochemical biosensor based on multi-wall carbon nanotube-modified screen-printed electrode immobilized by uricase for the detection of salivary uric acid.

Anal Bioanal Chem 2020 Oct 13;412(26):7275-7283. Epub 2020 Aug 13.

School of Public Health, Nantong University, Nantong, 226019, Jiangsu, China.

The amounts of uric acid (UA) in non-invasive biological samples, such as saliva, are critical for diagnosis and therapy of gout, hyperuricemia, Lesch-Nyhan syndrome, and several other diseases. Here, disposable UA biosensors were fabricated with the screen printing technique on the substrate of flexible PET. The working electrode was modified with carbon nanotubes followed by uricase for UA detection with excellent selectivity. Read More

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October 2020

Deep Brain Stimulation of the Internal Pallidum in Lesch-Nyhan Syndrome: Clinical Outcomes and Connectivity Analysis.

Neuromodulation 2021 Feb 23;24(2):380-391. Epub 2020 Jun 23.

Department of Neurosurgery, King's College Hospital NHS Foundation Trust, London, UK.

Background: Lesch-Nyhan syndrome (LNS) is a rare genetic disorder characterized by a deficiency of hypoxanthine-guanine phosphoribosyltransferase enzyme. It manifests during infancy with compulsive self-mutilation behavior associated with disabling generalized dystonia and dyskinesia. Clinical management of these patients poses an enormous challenge for medical teams and carers. Read More

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February 2021

A case of a 'rude' but not to be missed manifestation of epilepsy: ictal swearing.

J R Coll Physicians Edinb 2020 Mar;50(1):46-48

Department of Neurology, Haeundae Paik Hospital, Inje University College of Medicine, Haeundae-ro 875, Haeundae-gu, Busan 612896, Republic of Korea, Email:

Swearing is described in various neurological conditions such as Tourette syndrome, Lesch-Nyhan syndrome and post stroke or encephalitis. However, swearing as an ictal manifestation or automatism has rarely been reported. We herein describe a case with swearing as a predominant manifestation in focal epilepsy. Read More

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