1,400 results match your criteria Lesch-Nyhan Syndrome


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

Neuromodulation 2020 Jun 23. 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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1111/ner.13217DOI Listing

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

J R Coll Physicians Edinb 2020 03;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

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4997/JRCPE.2020.112DOI Listing

β-Amyloid precursor protein (APP) and the human diseases.

Authors:
Khue Vu Nguyen

AIMS Neurosci 2019 29;6(4):273-281. Epub 2019 Oct 29.

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.

Several pathophysiological functions of the human β-amyloid precursor protein (APP) have been recently proposed in different human diseases such as neurodevelopmental and neurodegenerative disorders including rare diseases such as autism, fragile X syndrome, amyotrophic lateral sclerosis, multiple sclerosis, Lesch-Nyhan disease; common and complex disorders such as Alzheimer's disease; metabolic disorders such as diabetes; and also cancer. APP as well as all of its proteolytic fragments including the amyloid-β (Aβ) peptide, are part of normal physiology. The targeting of the components of APP proteolytic processing as a pharmacologic strategy will not be without consequences. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.3934/Neuroscience.2019.4.273DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179352PMC
October 2019

Lesch-Nyhan disease: I. Construction of expression vectors for hypoxanthine-guanine phosphoribosyltransferase (HGprt) enzyme and amyloid precursor protein (APP).

Nucleosides Nucleotides Nucleic Acids 2020 20;39(6):905-922. Epub 2020 Apr 20.

Department of Pediatrics, School of Medicine, University of California, San Diego, California, USA.

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in HGprt enzyme activity can lead to the neurological syndrome, especially the self-injury of LND. Several studies have proposed different hypotheses regarding the etiology of this disease, and several treatments have been tried in patients. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/15257770.2020.1714653DOI Listing

Animal Model Contributions to Congenital Metabolic Disease.

Adv Exp Med Biol 2020 ;1236:225-244

Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, PA, USA.

Genetic model systems allow researchers to probe and decipher aspects of human disease, and animal models of disease are frequently specifically engineered and have been identified serendipitously as well. Animal models are useful for probing the etiology and pathophysiology of disease and are critical for effective discovery and development of novel therapeutics for rare diseases. Here we review the impact of animal model organism research in three examples of congenital metabolic disorders to highlight distinct advantages of model system research. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-981-15-2389-2_9DOI Listing

HPRT-related hyperuricemia with a novel p.V35M mutation in HPRT1 presenting familial juvenile gout.

CEN Case Rep 2020 Aug 3;9(3):210-214. Epub 2020 Mar 3.

Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.

Unlike complete deficiency of hypoxanthine phosphoribosyltransferase (HPRT) (i.e., Lesch-Nyhan syndrome), partial HPRT deficiency causes HPRT-related hyperuricemia without neurological symptoms. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s13730-020-00459-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320122PMC

Late diagnosis of Lesch-Nyhan disease complicated with end-stage renal disease and tophi burst: a case report.

Ren Fail 2020 Nov;42(1):113-121

Pediatric Nephrology Division, Department of Child Health, Faculty of Medicine, Cipto Mangunkusumo Hospital, University of Indonesia, Central Jakarta, Indonesia.

Lesch-Nyhan disease (LND) is a rare X-linked recessive inborn error of purine metabolism. Late diagnosis of LND may cause significant morbidity. LND cases have never been reported in Indonesia. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/0886022X.2020.1713805DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7034128PMC
November 2020

Anaesthetic management of a child with Lesch Nyhan syndrome.

Indian J Anaesth 2019 Dec 11;63(12):1051-1052. Epub 2019 Dec 11.

Department of Anaesthesia, Lady Hardinge Medical College and Smt. SK Hospital, New Delhi, India.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4103/ija.IJA_602_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6921318PMC
December 2019

Clinical outcome of prenatally suspected cardiac rhabdomyomas of the fetus.

J Perinat Med 2019 Dec;48(1):74-81

Department of Obstetrics, Charité - Universitätsmedizin Berlin, Berlin, Germany.

Background The main objective of this retrospective analysis in a large tertiary center was the clinical outcome of prenatally diagnosed cardiac rhabdomyomas as well as the identification of factors influencing fetal prognosis. Methods A total of 45 cases of fetuses with prenatally suspected rhabdomyoma and their clinical outcome were analyzed retrospectively. A review of the literature was also performed. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1515/jpm-2019-0246DOI Listing
December 2019

[Generation of cell strains containing point mutations in HPRT1 by CRISPR/Cas9].

Yi Chuan 2019 Oct;41(10):939-949

State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510006, China.

Mutations in Hypoxanthine-guanine Phosphoribosyltransferase1 (HPRT1) gene can lead to metabolic disorder of hypoxanthine and guanine metabolism, and other severe symptoms such as hypophrenia, gout, and kidney stones, called the Lesch-Nyhan disease (LND). Although the mutations are widely distributed throughout the HPRT1 gene, there are some isolated hot spots. In this study, we aim to introduce two previously reported hot spots, c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.16288/j.yczz.19-108DOI Listing
October 2019
1 Read

HPRT and Purine Salvaging Are Critical for Hematopoietic Stem Cell Function.

Stem Cells 2019 12 12;37(12):1606-1614. Epub 2019 Oct 12.

Institute of Molecular Medicine, Ulm University, Ulm, Germany.

Adult hematopoietic stem cells (HSCs) maintain tissue homeostasis and regenerative capacity of the hematopoietic system through self-renewal and differentiation. Metabolism is recognized as an important regulatory entity controlling stem cells. As purine nucleotides are essential for metabolic functions, we analyzed the role of hypoxanthine guanine phosphoribosyl transferase (HPRT)-associated purine salvaging in HSCs. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/stem.3087DOI Listing
December 2019
1 Read

Gout and the risk of advanced chronic kidney disease in the UK health system: a national cohort study.

BMJ Open 2019 08 28;9(8):e031550. Epub 2019 Aug 28.

OXON Epidemiology, London, UK.

Objective: Evaluate the association between gout and risk of advanced chronic kidney disease (CKD).

Design: Retrospective matched cohort study.

Setting: UK Clinical Practice Research Datalink. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1136/bmjopen-2019-031550DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6720233PMC
August 2019
3 Reads

Reduced Graphene Oxide-based Covalent Hybrid Film Electrode Self-assembled with Gold Nanoparticles for the Enzyme-Free Amperometric Sensing of Serum Uric Acid.

Authors:
Bhaskar Manna

Anal Sci 2020 Jan 23;36(1):121-126. Epub 2019 Aug 23.

Functional Materials and Electrochemistry Laboratory, Department of Chemistry, Indian Institute of Technology Kharagpur.

Purine metabolism in the human body leads to the production of uric acid (UA) at the end. But an abnormal level of UA in the human body creates health problems. The sensing and quantification of UA is essentially required to prevent and diagnose hypertension, arthritis, gout, hyperuricemia or Lesch-Nyhan syndrome, etc. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.2116/analsci.19P112DOI Listing
January 2020
1 Read

Positron Emission Tomography in Pediatric Neurodegenerative Disorders.

Authors:
Harry T Chugani

Pediatr Neurol 2019 11 17;100:12-25. Epub 2019 Jul 17.

Department of Neurology, NYU School of Medicine, New York, New York. Electronic address:

Application of molecular neuroimaging using positron emission tomographic techniques to assess pediatric neurodegenerative disorders has been limited, unlike in adults where positron emission tomography has contributed to clinical diagnosis, monitoring of neurodegenerative disease progression, and assessment of novel therapeutic approaches. Yet, there is a huge unexplored potential of molecular imaging to improve our understanding of the pathophysiology of neurodegenerative disorders in children and provide radiological biomarkers that can be applied clinically. The obstacles in performing PET scans on children include sedation, radiation exposure, and access but, as will be illustrated, these barriers can be easily overcome. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S08878994193042
Publisher Site
http://dx.doi.org/10.1016/j.pediatrneurol.2019.07.003DOI Listing
November 2019
4 Reads

Tongue Protrusion Dystonia in Pantothenate Kinase-Associated Neurodegeneration.

Pediatr Neurol 2020 02 13;103:76-78. Epub 2019 Jun 13.

Department of Neurology, Hazrat Rasool Hospital, Iran University of Medical Sciences, Tehran, Iran. Electronic address:

Background: Tongue protrusion dystonia is an uncommon focal dystonia involving the lingual muscles. Causes of tongue protrusion dystonia include tardive dystonia, posthypoxic dystonia, neuroacanthocytosis, pantothenate kinase-associated neurodegeneration, and Lesch-Nyhan syndrome.

Method: We summarize three children with pantothenate kinase-associated neurodegeneration and tongue protrusion dystonia. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pediatrneurol.2019.06.004DOI Listing
February 2020
8 Reads

Animal Models of Self-Injurious Behavior: An Update.

Authors:
Darragh P Devine

Methods Mol Biol 2019 ;2011:41-60

Behavioral and Cognitive Neuroscience Program, Department of Psychology, University of Florida, Gainesville, FL, USA.

Although self-injurious behavior is a common comorbid behavior problem among individuals with neurodevelopmental disorders, little is known about its etiology and underlying neurobiology. Interestingly, it shows up in various forms across patient groups with distinct genetic errors and diagnostic categories. This suggests that there may be shared neuropathology that confers vulnerability in these disparate groups. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/978-1-4939-9554-7_3DOI Listing

Clinical, biochemical and genetic characteristics of a cohort of 101 French and Italian patients with HPRT deficiency.

Mol Genet Metab 2019 06 3;127(2):147-157. Epub 2019 Jun 3.

Metabolic Biochemistry Laboratory, Hospital Necker Enfants Malades, APHP, University Paris Descartes, Paris, France.

Background: HPRT deficiency is a rare disorder of purine metabolism whose natural history is not fully understood. No optimal management recommendations exist. The objective of the present study is to characterize a large cohort of patients with HPRT deficiency, comparing Lesch-Nyhan Disease (LND) and its attenuated variants, with the purpose of helping clinicians in disease management and prognostic definition. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ymgme.2019.06.001DOI Listing
June 2019
8 Reads

Phenotypic and molecular spectrum of Korean patients with Lesch-Nyhan syndrome and attenuated clinical variants.

Metab Brain Dis 2019 10 25;34(5):1335-1340. Epub 2019 May 25.

Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Seoul, South Korea.

Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder caused by mutations in the HPRT1 gene. The clinical features and mutation spectrum of 26 Korean LNS patients from 23 unrelated families were retrospectively reviewed. The HPRT1 gene was analyzed by direct sequencing of genomic DNA. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11011-019-00441-0DOI Listing
October 2019
5 Reads

Microglial histamine HR in the pathophysiology of Parkinson's disease-a new actor on the stage?

Naunyn Schmiedebergs Arch Pharmacol 2019 06 24;392(6):641-645. Epub 2019 Apr 24.

Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, 30625, Hannover, Germany.

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00210-019-01635-0DOI Listing
June 2019
1 Read

Genetic mimics of cerebral palsy.

Mov Disord 2019 05 26;34(5):625-636. Epub 2019 Mar 26.

Department of Neurogenetics, Kolling Institute, Royal North Shore Hospital and University of Sydney, St Leonards, NSW, Australia.

The term "cerebral palsy mimic" is used to describe a number of neurogenetic disorders that may present with motor symptoms in early childhood, resulting in a misdiagnosis of cerebral palsy. Cerebral palsy describes a heterogeneous group of neurodevelopmental disorders characterized by onset in infancy or early childhood of motor symptoms (including hypotonia, spasticity, dystonia, and chorea), often accompanied by developmental delay. The primary etiology of a cerebral palsy syndrome should always be identified if possible. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1002/mds.27655DOI Listing
May 2019
23 Reads

Understanding the structure-function relationship of HPRT1 missense mutations in association with Lesch-Nyhan disease and HPRT1-related gout by in silico mutational analysis.

Comput Biol Med 2019 04 23;107:161-171. Epub 2019 Feb 23.

Department of Biomedical Sciences, College of Health and Sciences, Qatar University, Doha, Qatar. Electronic address:

The nucleotide salvage pathway is used to recycle degraded nucleotides (purines and pyrimidines); one of the enzymes that helps to recycle purines is hypoxanthine guanine phosphoribosyl transferase 1 (HGPRT1). Therefore, defects in this enzyme lead to the accumulation of DNA and nucleotide lesions and hence replication errors and genetic disorders. Missense mutations in hypoxanthine phosphoribosyl transferase 1 (HPRT1) are associated with deficiencies such as Lesch-Nyhan disease and chronic gout, which have manifestations such as arthritis, neurodegeneration, and cognitive disorders. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.compbiomed.2019.02.014DOI Listing
April 2019
20 Reads
1.240 Impact Factor

Analysis of synonymous codon usage patterns of HPRT1 gene across twelve mammalian species.

Genomics 2020 01 25;112(1):304-311. Epub 2019 Feb 25.

College of Agriculture, South China Agricultural University, Guangzhou, China. Electronic address:

Genetic changes in Hypoxanthine guanine phosphoribosyltransferace (HPRT1) gene can alter the expression of the dopamine neurotransmitter leads to abnormal neuron function, a disease called Lesch-Nyhan syndrome (LNS). Although different studies were conducted on LNS, information on codon usage bias (CUB) of HPRT1 gene is limited. The present study examines the genetic determinants of CUB in HPRT1 gene using twelve mammalian species. Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S08887543183073
Publisher Site
http://dx.doi.org/10.1016/j.ygeno.2019.02.010DOI Listing
January 2020
26 Reads
2.284 Impact Factor

Management of Self-injurious Behaviors in Children with Neurodevelopmental Disorders: A Pharmacotherapy Overview.

Pharmacotherapy 2019 06 27;39(6):645-664. Epub 2019 Mar 27.

Department of Pharmacy, Children's Hospital Colorado, Aurora, Colorado.

Neurodevelopmental disorders (NDDs), a group of disorders affecting ~1-2% of the general population, are caused by changes in brain development that result in behavioral and cognitive alterations, sensory and motor changes, and speech and language deficits. Neurodevelopmental disorders encompass a heterogeneous group of disorders including, but not limited to, Smith-Magenis syndrome, Lesch-Nyhan disease, cri du chat syndrome, Prader-Willi syndrome, pervasive developmental disorders, fragile X syndrome, Rett syndrome, Cornelia de Lange syndrome, and Down syndrome. Self-injurious behaviors (SIBs) are common in children with NDDs; depending on the specific NDD, the incidence of SIBs is nearly 100%. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1002/phar.2238
Publisher Site
http://dx.doi.org/10.1002/phar.2238DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6555654PMC
June 2019
11 Reads

Inhibiting PNP for the therapy of hyperuricemia in Lesch-Nyhan disease: Preliminary in vitro studies with analogues of immucillin-G.

J Inherit Metab Dis 2019 01;42(1):178-185

Department of Biotechnology, Chemistry, and Pharmacy, University of Siena, Via A. Moro 2, 53100 Siena, Italy.

Lesch-Nyhan disease (LND) is a rare X-linked genetic disorder, with complete hypoxanthine-guanine phosphoribosyltransferase (HGPRT) deficiency, uric acid (UA), hypoxanthine and xanthine accumulation, and a devastating neurologic syndrome. UA excess, causing renal failure, is commonly decreased by xanthine oxidoreductase (XOR) inhibitors, such as allopurinol, yielding a xanthine and hypoxanthine increase. Xanthine accumulation may result in renal stones, while hypoxanthine excess seems involved in the neurological disorder. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1002/jimd.12039
Publisher Site
http://dx.doi.org/10.1002/jimd.12039DOI Listing
January 2019
14 Reads

Intellectual Disability and Psychotropic Medications.

J Dev Behav Pediatr 2018 09;39(7):591-593

Division of Developmental Behavioral Pediatrics, University of Michigan Medical School, Ann Arbor, MI.

Case: Andrew is a 17-year-old male with trisomy 21, commonly known as Down syndrome, and accompanying severe intellectual disability who presents to your primary care office with his father for the first time to establish care and assistance with transition. Andrew has a history of a complete atrioventricular canal that was repaired as an infant and poorly controlled infantile spasms. Currently, he struggles with constipation, esophageal strictures, medullary nephrocalcinosis, urinary retention, sleep dysregulation, G-tube dependency, and hip dysplasia. Read More

View Article

Download full-text PDF

Source
http://Insights.ovid.com/crossref?an=00004703-900000000-9926
Publisher Site
http://dx.doi.org/10.1097/DBP.0000000000000613DOI Listing
September 2018
63 Reads

Recurrent kidney stones in a child with Lesch-Nyhan syndrome: Answers.

Pediatr Nephrol 2019 03 15;34(3):425-427. Epub 2018 Aug 15.

Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s00467-018-4037-9
Publisher Site
http://dx.doi.org/10.1007/s00467-018-4037-9DOI Listing
March 2019
8 Reads

Recurrent kidney stones in a child with Lesch-Nyhan syndrome: Questions.

Pediatr Nephrol 2019 03 15;34(3):423-424. Epub 2018 Aug 15.

Royal Manchester Children's Hospital, Manchester, M13 9WL, UK.

View Article

Download full-text PDF

Source
http://link.springer.com/10.1007/s00467-018-4035-y
Publisher Site
http://dx.doi.org/10.1007/s00467-018-4035-yDOI Listing
March 2019
10 Reads

Compositional complexity of rods and rings.

Mol Biol Cell 2018 09 19;29(19):2303-2316. Epub 2018 Jul 19.

Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.

Rods and rings (RRs) are large linear- or circular-shaped structures typically described as polymers of IMPDH (inosine monophosphate dehydrogenase). They have been observed across a wide variety of cell types and species and can be induced to form by inhibitors of IMPDH. RRs are thought to play a role in the regulation of de novo guanine nucleotide synthesis; however, the function and regulation of RRs is poorly understood. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1091/mbc.E18-05-0274DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6249804PMC
September 2018
17 Reads

Xanthine calculi in a patient with Lesch-Nyhan syndrome and factor V Leiden treated with allopurinol: case report.

BMC Pediatr 2018 07 12;18(1):231. Epub 2018 Jul 12.

Norton Children's Urology, Norton Healthcare, Louisville, KY, 40207, USA.

Background: Lesch-Nyhan syndrome is a rare inborn error of purine metabolism marked by a complete deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Inherited as an X-linked recessive genetic disorder that primarily affects males, patients with Lesch-Nyhan syndrome exhibit severe neurological impairments, including choreoathetosis, ballismus, cognitive dysfunction, and self-injurious behavior. Uric acid levels are usually abnormally high, leading to kidney and bladder stones which often necessitate urological intervention. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12887-018-1197-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043999PMC
July 2018
24 Reads

Congenital and acquired diseases related to stone formation.

Curr Opin Urol 2018 09;28(5):414-419

Department of Urology, Medical University, General Hospital Vienna, Wahringer Gurtel 18-20, Vienna, Austria.

Purpose Of Review: To summarize the latest findings of congenital and acquired diseases related to stone formation and help understanding the multitude of cofactors related to urolithiasis.

Recent Findings: Urolithiasis is related to a broad spectrum of congenital and acquired diseases and its management varies according to the stone type, underlying disease or recurrence rate, but it also changes according to recent findings and developments. As prevalence of urolithiasis is constantly increasing, identification of high-risk stone formers and early treatment is essential. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/MOU.0000000000000522DOI Listing
September 2018
33 Reads

GLUT9 influences uric acid concentration in patients with Lesch-Nyhan disease.

Int J Rheum Dis 2018 Jun;21(6):1270-1276

Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital, IdiPaz, Madrid, Spain.

Background: Patients with deficient hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity present hyperuricemia and/or hyperuricosuria, with a variable degree of neurological manifestations. Hyperuricemia in HPRT deficiency is due to uric acid overproduction and is frequently treated with allopurinol. Renal uric acid excretion is sharply increased in these patients. Read More

View Article

Download full-text PDF

Source
http://doi.wiley.com/10.1111/1756-185X.13323
Publisher Site
http://dx.doi.org/10.1111/1756-185X.13323DOI Listing
June 2018
23 Reads

Macrocytic anemia in Lesch-Nyhan disease and its variants.

Genet Med 2019 02 6;21(2):353-360. Epub 2018 Jun 6.

Department of Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.

Purpose: Lesch-Nyhan disease is an inherited metabolic disorder characterized by overproduction of uric acid and neurobehavioral abnormalities. The purpose of this study was  to describe macrocytic erythrocytes as another common aspect of the phenotype.

Methods: The results of 257 complete blood counts from 65 patients over a 23-year period were collected from 2 reference centers where many patients are seen regularly. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-018-0053-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281870PMC
February 2019
42 Reads

A review of HPRT and its emerging role in cancer.

Med Oncol 2018 May 5;35(6):89. Epub 2018 May 5.

Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT, USA.

Hypoxanthine guanine phosphoribosyltransferase (HPRT) is a common salvage housekeeping gene with a historically important role in cancer as a mutational biomarker. As an established and well-known human reporter gene for the evaluation of mutational frequency corresponding to cancer development, HPRT is most commonly used to evaluate cancer risk within individuals and determine potential carcinogens. In addition to its use as a reporter gene, HPRT also has important functionality in the body in relation to purine regulation as demonstrated by Lesch-Nyhan patients whose lack of functional HPRT leads to significant purine overproduction and further neural complications. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12032-018-1144-1DOI Listing
May 2018
7 Reads

Oral self-mutilation in Lesch-Nyhan Syndrome. Case Report.

Rev Chil Pediatr 2018 Feb;89(1):86-91

Unidad de Neurología Pediátrica, División de Pediatría, Escuela de Medicina, Pontificia Universidad Católica de Chile, Chile.

Introduction: Lesch-Nyhan syndrome (LNS) is an inherited recessive X-related disorder caused by the deficiency of the enzyme hypoxanthin-guanine phosphorribosyl transferase (HPRT). Compul sive self-mutilation and dystonia occurs before the first year of age and is expressed by persistent bites on the oral mucosa, lips, tongue, fingers, and shoulders. The dental intervention performed on most of these patients is multiple tooth extraction to prevent serious secondary lesions. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4067/S0370-41062018000100086DOI Listing
February 2018
8 Reads

Inborn Errors of Metabolism with Cognitive Impairment: Metabolism Defects of Phenylalanine, Homocysteine and Methionine, Purine and Pyrimidine, and Creatine.

Pediatr Clin North Am 2018 04;65(2):267-277

Division of Medical Genetics, Department of Pediatrics, Children's Hospital of Pittsburgh, University of Pittsburgh, UPMC, 4401 Penn Avenue, Pittsburgh, PA 15224, USA. Electronic address:

Phenylketonuria is a defect in phenylalanine metabolism resulting in the excretion of phenylketones and severe intellectual disability. The principle of eliminating the offending amino acid from the diet as a successful treatment strategy was demonstrated. The development of a low methionine diet to treat homocystinuria was established after identifying the transsulfuration pathway resulting in cysteine synthesis. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.pcl.2017.11.009DOI Listing
April 2018
15 Reads

Lesch-Nyhan Syndrome in a Chinese Family with Mutation in the Hypoxanthine-Guanine Phosphoribosyltransferase Gene.

Clin Lab 2018 Jan;64(1):197-200

Background: Lesch-Nyhan syndrome (LNS) is a congenital X-linked recessive neurogenetic disorder caused by mutations in the hypoxanthine-guanine phosphoribosyltransferase (HPRT) gene. The main clinical manifestation includes hyperuricemia, juvenile-onset gouty arthritis, and neurological developmental disorders. Studies have reported more than 400 HPRT gene mutation sites, but the incidence of LNS in the Chinese population is extremely low. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.7754/Clin.Lab.2017.170813DOI Listing
January 2018
9 Reads

Leveraging Rational Protein Engineering to Improve mRNA Therapeutics.

Nucleic Acid Ther 2018 04 13;28(2):74-85. Epub 2018 Feb 13.

1 Discovery Research, Alexion Pharmaceuticals, Inc. , Cambridge, Massachusetts.

Messenger RNA (mRNA) is a promising new class of therapeutics that has potential for treatment of diseases in fields such as immunology, oncology, vaccines, and inborn errors of metabolism. mRNA therapy has several advantages over DNA-based gene therapy, including the lack of the need for nuclear import and transcription, as well as limited possibility of genomic integration. One drawback of mRNA therapy, especially in cases such as metabolic disorders where repeated dosing will be necessary, is the relatively short in vivo half-life of mRNA (∼6-12 h). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1089/nat.2017.0697DOI Listing
April 2018
9 Reads

Altered gastrointestinal motility in an animal model of Lesch-Nyhan disease.

Auton Neurosci 2018 03 20;210:55-64. Epub 2017 Dec 20.

Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy.

Mutations in the HGPRT1 gene, which encodes hypoxanthine-guanine phosphoribosyltransferase (HGprt), housekeeping enzyme responsible for recycling purines, lead to Lesch-Nyhan disease (LND). Clinical expression of LND indicates that HGprt deficiency has adverse effects on gastrointestinal motility. Therefore, we aimed to evaluate intestinal motility in HGprt knockout mice (HGprt¯). Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.autneu.2017.12.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5904834PMC
March 2018
77 Reads

Lesch-Nyhan syndrome and its variants: examining the behavioral and neurocognitive phenotype.

Authors:
James C Harris

Curr Opin Psychiatry 2018 03;31(2):96-102

The Johns Hopkins University School of Medicine, Charlotte R. Bloomberg Children's Center, Baltimore, Maryland, USA.

Purpose Of Review: Lesch-Nyhan Syndrome (LNS) is a metabolic disorder involving mutations in the HGPRT1 gene that result in hyperuricemia, intellectual disability, a dystonic movement disorder, and compulsive self-injury with self-mutilation. The aim of this review is to summarize recent research that documents the extended behavioral, neurologic, and neurocognitive phenotype in classic LNS, to describe milder variants of HGprt deficiency that do not self-injure and have less severe neurological and cognitive deficits, and to provide an update on treatment for associated psychiatric and behavioral disorders.

Recent Findings: Psychiatric management utilizes combined behavioral and pharmacological treatment in conjunction with protective equipment and dental management to avert self-injury. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1097/YCO.0000000000000388DOI Listing
March 2018
77 Reads

Novel mutation in the human HPRT1 gene and the Lesch-Nyhan disease.

Nucleosides Nucleotides Nucleic Acids 2017 Nov 29;36(11):704-711. Epub 2017 Nov 29.

b Department of Pediatrics, School of Medicine , University of California, San Diego , CA , USA.

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report a novel point mutation that led to HGprt-related neurological dysfunction (HND) in a family in which there was a missense mutation in exon 6 of the coding region of the HPRT1 gene: g.34938G>T, c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/15257770.2017.1395037DOI Listing
November 2017
20 Reads

Skewed X inactivation in Lesch-Nyhan disease carrier females.

J Hum Genet 2017 Dec 14;62(12):1079-1083. Epub 2017 Sep 14.

Department of Internal Medicine, Metabolic-Vascular Unit, La Paz University Hospital, Madrid, Spain.

X chromosome inactivation (XCI) ratios of normal females can range from a highly skewed ratio of 0:100 to a 50:50 ratio. In several X-linked disorders, female carriers present skewed X inactivation. Hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency is an X-linked disorder. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1038/jhg.2017.88DOI Listing
December 2017
9 Reads

Uric acid, an important screening tool to detect inborn errors of metabolism: a case series.

BMC Res Notes 2017 Sep 6;10(1):454. Epub 2017 Sep 6.

Institute of Rheumatology, Prague, Czech Republic and Institute of Inherited Metabolic Disorders, First Faculty of Medicine, Charles University, Prague, Czech Republic.

Background: Uric acid is the metabolic end product of purine metabolism in humans. Altered serum and urine uric acid level (both above and below the reference ranges) is an indispensable marker in detecting rare inborn errors of metabolism. We describe different case scenarios of 4 Sri Lankan patients related to abnormal uric acid levels in blood and urine. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13104-017-2795-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588617PMC
September 2017
67 Reads

A Case of Attempted Bilateral Self-Enucleation in a Patient with Bipolar Disorder.

Ment Illn 2017 Mar 26;9(1):7141. Epub 2017 Jun 26.

Department of Ophthalmology, Gavin Herbert Eye Institute, CA, USA.

Attempted and completed self-enucleation, or removal of one's own eyes, is a rare but devastating form of self-mutilation behavior. It is often associated with psychiatric disorders, particularly schizophrenia, substance induced psychosis, and bipolar disorder. We report a case of a patient with a history of bipolar disorder who gouged his eyes bilaterally as an attempt to self-enucleate himself. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.4081/mi.2017.7141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509962PMC
March 2017
43 Reads

CRISPR/Cas9-Mediated Scanning for Regulatory Elements Required for HPRT1 Expression via Thousands of Large, Programmed Genomic Deletions.

Am J Hum Genet 2017 Aug 14;101(2):192-205. Epub 2017 Jul 14.

Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA; Howard Hughes Medical Institute, Seattle, WA 98195, USA. Electronic address:

The extent to which non-coding mutations contribute to Mendelian disease is a major unknown in human genetics. Relatedly, the vast majority of candidate regulatory elements have yet to be functionally validated. Here, we describe a CRISPR-based system that uses pairs of guide RNAs (gRNAs) to program thousands of kilobase-scale deletions that deeply scan across a targeted region in a tiling fashion ("ScanDel"). Read More

View Article

Download full-text PDF

Source
https://linkinghub.elsevier.com/retrieve/pii/S00029297173024
Publisher Site
http://dx.doi.org/10.1016/j.ajhg.2017.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544381PMC
August 2017
23 Reads

Self-injurious behavior.

Neurosci Biobehav Rev 2018 Jan 8;84:483-491. Epub 2017 Jul 8.

Department of Pediatrics, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, the Netherlands.

Self-injurious behavior (SIB) is a relatively common behavior in individuals with intellectual disabilities (ID). Severe SIB can be devastating and potentially life-threatening. There is increasing attention for somatic substrates of behavior in genetic syndromes, and growing evidence of an association between pain and discomfort with SIB in people with ID and genetic syndromes. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.neubiorev.2017.02.027DOI Listing
January 2018
56 Reads

Lesch-Nyhan disease in two families from Chiloé Island with mutations in the HPRT1 gene.

Nucleosides Nucleotides Nucleic Acids 2017 Jul 19;36(7):452-462. Epub 2017 May 19.

b Department of Pediatrics , University of California, San Diego, School of Medicine , San Diego, La Jolla , California , USA.

Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report two independent point mutations leading to splicing errors: IVS 2 +1G>A, c.134 +1G>A, and IVS 3 +1G>A, c. Read More

View Article

Download full-text PDF

Source
http://dx.doi.org/10.1080/15257770.2017.1315434DOI Listing
July 2017
43 Reads