1,369 results match your criteria Lesch-Nyhan Syndrome


Intellectual Disability and Psychotropic Medications.

J Dev Behav Pediatr 2018 Sep;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

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

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

Pediatr Nephrol 2018 Aug 15. Epub 2018 Aug 15.

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

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http://dx.doi.org/10.1007/s00467-018-4037-9DOI Listing

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

Pediatr Nephrol 2018 Aug 15. Epub 2018 Aug 15.

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

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http://dx.doi.org/10.1007/s00467-018-4035-yDOI Listing

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

BMC Pediatr 2018 Jul 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

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http://dx.doi.org/10.1186/s12887-018-1197-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043999PMC
July 2018
10 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

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http://doi.wiley.com/10.1111/1756-185X.13323
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http://dx.doi.org/10.1111/1756-185X.13323DOI Listing
June 2018
6 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 2018 Jun 4. Epub 2018 Jun 4.

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

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http://dx.doi.org/10.1007/s10545-018-0196-xDOI Listing
June 2018
3 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

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http://dx.doi.org/10.1007/s12032-018-1144-1DOI Listing
May 2018
2 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

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

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

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http://dx.doi.org/10.1016/j.pcl.2017.11.009DOI Listing
April 2018
5 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

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http://dx.doi.org/10.7754/Clin.Lab.2017.170813DOI Listing
January 2018
2 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

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

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

Authors:
James C Harris

Curr Opin Psychiatry 2018 Mar;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

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http://dx.doi.org/10.1097/YCO.0000000000000388DOI Listing
March 2018
46 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

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http://dx.doi.org/10.1080/15257770.2017.1395037DOI Listing
November 2017
12 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

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http://dx.doi.org/10.1038/jhg.2017.88DOI Listing
December 2017
5 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

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http://dx.doi.org/10.1186/s13104-017-2795-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5588617PMC
September 2017
18 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

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http://dx.doi.org/10.4081/mi.2017.7141DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5509962PMC
March 2017
5 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

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https://linkinghub.elsevier.com/retrieve/pii/S00029297173024
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http://dx.doi.org/10.1016/j.ajhg.2017.06.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544381PMC
August 2017
9 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

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http://dx.doi.org/10.1016/j.neubiorev.2017.02.027DOI Listing
January 2018
25 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

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

A Trivalent Enzymatic System for Uricolytic Therapy of HPRT Deficiency and Lesch-Nyhan Disease.

Pharm Res 2017 Jul 15;34(7):1477-1490. Epub 2017 May 15.

Department of Medicine and Surgery,, University of Parma, Parco Area delle Scienze 23/A, 43124, Parma, Italy.

Purpose: Because of the evolutionary loss of the uricolytic pathway, humans accumulate poorly soluble urate as the final product of purine catabolism. Restoration of uricolysis through enzyme therapy is a promising treatment for severe hyperuricemia caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). To this end, we studied the effect of PEG conjugation on the activity and stability of the enzymatic complement required for conversion of urate into the more soluble (S)-allantoin. Read More

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http://dx.doi.org/10.1007/s11095-017-2167-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5445154PMC
July 2017
21 Reads

Lesch-Nyhan syndrome: The saga of metabolic abnormalities and self-injurious behavior.

Intractable Rare Dis Res 2017 Feb;6(1):65-68

Pedodontics & Preventive Dentistry, Center for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India.

Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder of purine metabolism caused by a mutation in Xq26.2-q26.3 (OMIM 308000. Read More

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https://www.jstage.jst.go.jp/article/irdr/6/1/6_2016.01076/_
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http://dx.doi.org/10.5582/irdr.2016.01076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5359358PMC
February 2017
3 Reads

The renal phenotype of allopurinol-treated HPRT-deficient mouse.

PLoS One 2017 10;12(3):e0173512. Epub 2017 Mar 10.

Department of Life Sciences, University of Parma, Parma, Italy.

Excess of uric acid is mainly treated with xanthine oxidase (XO) inhibitors, also called uricostatics because they block the conversion of hypoxanthine and xanthine into urate. Normally, accumulation of upstream metabolites is prevented by the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme. The recycling pathway, however, is impaired in the presence of HPRT deficiency, as observed in Lesch-Nyhan disease. Read More

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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0173512PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5345830PMC
August 2017
4 Reads

Quantification of various APP-mRNA isoforms and epistasis in Lesch-Nyhan disease.

Neurosci Lett 2017 03 10;643:52-58. Epub 2017 Feb 10.

Department of Pediatrics, University of California, San Diego, School of Medicine, San Diego, La Jolla, CA, 92093, USA.

The present work is the development of a simple and specific kinetic method based on RT-PCR technique coupled with direct sequencing for quantification of various amyloid precursor protein-mRNA isoforms (APP-mRNA isoforms) in biological samples, especially for identifying the most abundant one that may decisive for the normal status or disease risk. Application of this kinetic method to the Lesch-Nyhan disease (LND) was performed and results indicated an epistasis between mutated hypoxanthine phosphoribosyltransferase1 (HPRT1) and APP genes. APP-mRNA isoform of 624bp, with a deletion starting after 49bp of the 5' end of exon 3 followed by a complete deletion of exons 4-15, mutations in exon 1: c. Read More

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http://dx.doi.org/10.1016/j.neulet.2017.02.016DOI Listing
March 2017
7 Reads

Oral Hemorrhage in a 3-year-old Boy Caused by Self-Mutilating Behavior.

Pak J Med Sci 2016 Nov-Dec;32(6):1583-1585

Prof. Dr. José Florencio F. Lapeña, Jr., MA, MD. Department of Otorhinolaryngology, College of Medicine, Philippine General Hospital, University of the Philippines Manila, Philippines.

A 3-year-old boy referred for persistent tongue bleeding was diagnosed with a rare self-mutilating disease that had also affected his lip and fingers. He underwent multiple odontectomy and partial glossectomy and continues to undergo behavior therapy and on-demand splints and restraints. He has stopped self-biting and has gained appetite and weight. Read More

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http://dx.doi.org/10.12669/pjms.326.12088DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5216325PMC
January 2017
2 Reads

Human HPRT1 gene and the Lesch-Nyhan disease: Substitution of alanine for glycine and inversely in the HGprt enzyme protein.

Nucleosides Nucleotides Nucleic Acids 2017 Feb 3;36(2):151-157. Epub 2017 Jan 3.

b Department of Pediatrics , University of California, San Diego, School of Medicine , San Diego, La Jolla , 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 three novel independent mutations in the coding region of the HPRT1 gene from genomic DNA of (a) a carrier sister of two male patients with LND: c.569G>C, p. Read More

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http://dx.doi.org/10.1080/15257770.2016.1231319DOI Listing
February 2017
6 Reads

Treatment of self-injurious behaviors in Lesch-Nyhan syndrome with S-adenosylmethionine.

No To Hattatsu 2017 Jan;49(1):25-7

An 11-year-old boy with Lesch-Nyhan syndrome (LNS) had persistently injured himself by biting his lips and buccal mucosa since infancy. Risperidone was only partially effective in suppressing this behavior. Oral administration of S-adenosylmethionine (SAMe), involving increasing the dose from 400 mg to 1 g, resulted in the amelioration of self-injurious behavior and anxiety as well as marked improvement in his self-esteem, performance at school, and friendships. Read More

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January 2017

[Recent advances in urate metabolism].

G Ital Nefrol 2016 Malattie Metaboliche e Rene;33(S68)

In the last fifteen years, genomics and other -omics sciences have revolutionized our understanding of biological processes at the molecular level. An illustrative example is urate metabolism. Before the publication of the complete human genome, in 2003 it was believed that a single enzyme (urate oxidase) was responsible for uricolysis that is the conversion of urate into the more soluble allantoin. Read More

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October 2017
8 Reads

Lesch-Nyhan Syndrome: Models, Theories, and Therapies.

Mol Syndromol 2016 Nov 24;7(6):302-311. Epub 2016 Sep 24.

Department of Psychiatry, Douglas Hospital Research Institute, McGill University, Montreal, Que., Canada.

Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by mutations in HPRT1, an important enzyme in the purine salvage pathway. Symptoms of LNS include dystonia, gout, intellectual disability, and self-mutilation. Despite having been characterized over 50 years ago, it remains unclear precisely how deficits in hypoxanthine and guanine recycling can lead to such a profound neurological phenotype. Read More

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http://dx.doi.org/10.1159/000449296DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5131334PMC
November 2016
3 Reads

A review of the implication of hypoxanthine excess in the physiopathology of Lesch-Nyhan disease.

Nucleosides Nucleotides Nucleic Acids 2016 Dec;35(10-12):507-516

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

Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. Read More

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http://dx.doi.org/10.1080/15257770.2016.1147579DOI Listing
December 2016
2 Reads

Development of new forms of self-injurious behavior following total dental extraction in Lesch-Nyhan disease.

Nucleosides Nucleotides Nucleic Acids 2016 Dec;35(10-12):524-528

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

We report two Lesch-Nyhan Disease (LND) patients who developed new forms of self-injurious behavior following total dental extraction. Patients 1 and 2 were submitted to total teeth extraction at the age of 13 and 8 years, respectively, due to continuous self-biting, not prevented by mouth guards. Severity of dystonia was markedly reduced and quality of life improved. Read More

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http://dx.doi.org/10.1080/15257770.2016.1184276DOI Listing
December 2016
4 Reads

Self-injurious Behavior in a Young Child with Lesch-Nyhan Syndrome.

Indian J Psychol Med 2016 Sep-Oct;38(5):477-479

Department of Psychiatry, Mental Health Institute, S.C.B. Medical College, Cuttack, Odisha, India.

Lesch-Nyhan syndrome (LNS) is a rare inherited disorder caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase-1. Few reports on behavioral aspects especially self-injurious behavior in LNS patients are available. We report a case of LNS in an 8-year-old male child, who presented with characteristic self-injurious behavior. Read More

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http://dx.doi.org/10.4103/0253-7176.191389DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5052966PMC
November 2016
4 Reads

Novel mutation in HPRT1 causing a splicing error with multiple variations.

Nucleosides Nucleotides Nucleic Acids 2017 Jan 18;36(1):1-6. Epub 2016 Oct 18.

a Department of Child Neurology , National Center Hospital, National Center of Neurology and Psychiatry (NCNP) , Tokyo , Japan.

Lesch-Nyhan disease (LND) is a rare X-linked recessive disorder caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT), encoded by the HPRT1. To date, nearly all types of mutations have been reported in the whole gene; however, duplication mutations are rare. We here report the case of a 9-month-old boy with LND. Read More

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http://dx.doi.org/10.1080/15257770.2016.1163381DOI Listing
January 2017
4 Reads

HPRTYale proposed as a pathogenic variant for Lesch-Nyhan syndrome: a case report.

Genet Mol Res 2016 Jun 24;15(2). Epub 2016 Jun 24.

Núcleo de Genética Humana e Molecular, Departamento de Ciências Biológicas, Universidade Federal do Espírito Santo, Vitória, ES, Brasil.

Lesch-Nyhan syndrome (LNS) is an X-linked recessive disorder caused by a deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT), an enzyme encoded by the HPRT1 gene. The classic disease phenotype described by Lesch and Nyhan in 1964 includes hyperuricemia, mental retardation, severe motor deficiency, and recurring self-mutilation. Here, we report the case of a family with 4 affected males and several female obligate carriers. Read More

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http://dx.doi.org/10.4238/gmr.15028251DOI Listing
June 2016
2 Reads

Mutation in the Human HPRT1 Gene and the Lesch-Nyhan Syndrome.

Nucleosides Nucleotides Nucleic Acids 2016 Aug 5;35(8):426-33. Epub 2016 Jul 5.

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

Lesch-Nyhan syndrome (LNS) 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 mutation which led to HGprt-related neurological dysfunction (HND) in two brothers from the same family with a missense mutation in exon 6 of the coding region of the HPRT1 gene: c.437T>C, p. Read More

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http://dx.doi.org/10.1080/15257770.2015.1098660DOI Listing
August 2016
3 Reads

Lesch-Nyhan Syndrome: Disorder of Self-mutilating Behavior.

Int J Clin Pediatr Dent 2016 Apr-Jun;9(2):139-42. Epub 2016 Jun 15.

Postgraduate Student, Department of Pedodontics and Preventive Dentistry, Sinhgad Dental College and Hospital, Pune, Maharashtra, India.

Lesch-Nyhan syndrome (LNS), a rare inborn error of metabolism, is characterized by self-injurious behavior, which results in partial or total destruction of oral and perioral tissues and/ or fingers. Persistent self-injurious behavior (biting the fingers, hands, lips, and cheeks; banging the head or limbs) is a hallmark of the disease. Prevention of self-mutilation raises significant difficulties. Read More

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http://dx.doi.org/10.5005/jp-journals-10005-1350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4921883PMC
July 2016
3 Reads

Towards rational drug treatment of Lesch-Nyhan disease.

Authors:
Roland Seifert

Mol Genet Metab 2016 07 9;118(3):145-6. Epub 2016 May 9.

Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Straße 1, D-30625 Hannover, Germany. Electronic address:

Lesch-Nyhan disease (LND) is a rare X-chromosomal purine metabolism disorder. LND is characterized by self-injurious behavior (SIB) for which there is no drug treatment. This commentary places a recent clinical study by Khasnavis et al. Read More

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http://dx.doi.org/10.1016/j.ymgme.2016.05.004DOI Listing
July 2016
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Neurotransmitter and their metabolite concentrations in different areas of the HPRT knockout mouse brain.

J Neurol Sci 2016 Jun 16;365:169-74. Epub 2016 Apr 16.

Institute of Pharmacology, Hannover Medical School, Hannover, Germany; Research Core Unit Metabolomics, Hannover Medical School, Hannover, Germany. Electronic address:

Lesch-Nyhan syndrome (LNS) is characterized by uric acid overproduction and severe neurobehavioral symptoms, such as recurrent self-mutilative behavior. To learn more about the pathophysiology of the disease, we quantified neurotransmitters and their metabolites in the cerebral hemisphere, cerebellum and the medulla oblongata of HPRT knockout mice, an animal model for LNS, in comparison to the corresponding wild-type. Our analyses included l-glutamate, 4-aminobutanoic acid (GABA), acetylcholine, serotonin, 5-hydroxyindoleacetic acid (5-HIAA), norepinephrine, l-normetanephrine, epinephrine and l-metanephrine and were conducted via high performance liquid chromatography (HPLC) coupled to tandem mass spectrometry (MS/MS). Read More

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http://dx.doi.org/10.1016/j.jns.2016.04.025DOI Listing
June 2016
11 Reads

Acute renal failure unmasking Lesch-Nyhan disease in a patient with tuberous sclerosis complex.

Eur J Paediatr Neurol 2016 Jul 3;20(4):649-51. Epub 2016 May 3.

Department of Pediatric Nephrology, Charité, Berlin, Germany.

Case Report: We report on a male patient with Tuberous Sclerosis Complex (TSC), which was prenatally diagnosed. At the age of 3 months the patient developed acute renal failure with excessive hyperuricemia. Kidney function improved after rehydration and application of rasburicase, however without full recovery. Read More

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http://dx.doi.org/10.1016/j.ejpn.2016.04.014DOI Listing
July 2016
27 Reads

Reduced levels of dopamine and altered metabolism in brains of HPRT knock-out rats: a new rodent model of Lesch-Nyhan Disease.

Sci Rep 2016 05 17;6:25592. Epub 2016 May 17.

The Roslin Institute and R(D)VS, University of Edinburgh, Easter Bush, Midlothian, EH25 9RG, Scotland.

Lesch-Nyhan disease (LND) is a severe neurological disorder caused by loss-of-function mutations in the gene encoding hypoxanthine phosphoribosyltransferase (HPRT), an enzyme required for efficient recycling of purine nucleotides. Although this biochemical defect reconfigures purine metabolism and leads to elevated levels of the breakdown product urea, it remains unclear exactly how loss of HPRT activity disrupts brain function. As the rat is the preferred rodent experimental model for studying neurobiology and diseases of the brain, we used genetically-modified embryonic stem cells to generate an HPRT knock-out rat. Read More

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http://dx.doi.org/10.1038/srep25592DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4869022PMC
May 2016
7 Reads

A double-blind, placebo-controlled, crossover trial of the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease.

Mol Genet Metab 2016 07 24;118(3):160-6. Epub 2016 Apr 24.

Department of Neurology, Emory University, Atlanta, GA 30322, USA; Department of Human Genetics, Emory University, Atlanta, GA 30322, USA; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address:

Lesch-Nyhan disease (LND) is a genetic disorder that has characteristic metabolic, neurologic, and behavioral features. There are multiple behavioral problems including impulsivity, aggressiveness, and severe recurrent self-injurious behavior (SIB). This last behavior varies considerably across subjects and may encompass self-biting, self-hitting, scratching, head banging, and other injurious actions. Read More

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http://dx.doi.org/10.1016/j.ymgme.2016.04.012DOI Listing
July 2016
3 Reads

Overcoming the oral aspects of -self-mutilation: description of a method.

Spec Care Dentist 2016 Sep 22;36(5):282-7. Epub 2016 Apr 22.

Department of Orthodontics, Hebrew University - Hadassah School of Dental Medicine, Jerusalem, Israel.

Background/aim: Self-injurious behavior (SIB) is a serious and chronic condition frequently seen in special needs populations, affecting 10% to 17% of individuals diagnosed with intellectual and/or developmental disabilities. A 2.5-year-old infant with SIB, whose presenting symptoms were severe tongue and lip lacerations accompanied by much hemorrhage, is presented here to illustrate the problem and to show how this may be prevented. Read More

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http://dx.doi.org/10.1111/scd.12181DOI Listing
September 2016
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Nephrocalcinosis and Renal Failure in Lesch-Nyhan Syndrome: Report of Two Familial Cases and Review of the Literature.

Urology 2016 11 11;97:194-196. Epub 2016 Apr 11.

1st Department of Pediatrics, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece. Electronic address:

Lesch-Nyhan syndrome is an X-linked recessive inborn error of purine metabolism, due to deficiency of the enzyme HPRT (hypoxanthine-guanine phosphoribosyl transferase) and underlying HPRT gene mutations (over 300 mutations identified up to date). It is characterized by a wide range of neurological symptoms and signs (mainly a combination of spastic diplegia with choreoathetosis and an overall psychomotor redardation). Herein, we report of two cousins with Lesch-Nyhan syndrome and a confirmed novel HPRT gene mutation: c. Read More

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http://dx.doi.org/10.1016/j.urology.2016.04.004DOI Listing
November 2016
6 Reads

The Use of Perinatal 6-Hydroxydopamine to Produce a Rodent Model of Lesch-Nyhan Disease.

Curr Top Behav Neurosci 2016;29:265-277

School of Medicine, Department of Psychiatry and Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, NC, 27599, USA.

Lesch-Nyhan disease is a neurologically, metabolically, and behaviorally devastating condition that has eluded complete characterization and adequate treatment. While it is known that the disease is intimately associated with dysfunction of the hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene that codes for an enzyme of purine metabolism (hypoxanthine-guanine phosphoribosyltransferase) and is associated with neurological, behavioral, as well as metabolic dysfunction, the mechanisms of the neurobehavioral manifestations are as yet unclear. However, discoveries over the past few decades not only have created useful novel animal models (e. Read More

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http://dx.doi.org/10.1007/7854_2016_444DOI Listing
June 2017
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A clinical trial of safety and tolerability for the selective dopamine D1 receptor antagonist ecopipam in patients with Lesch-Nyhan disease.

Mol Genet Metab 2016 Apr 18;117(4):401-6. Epub 2016 Feb 18.

Department of Neurology, Emory University, Atlanta, GA 30322, USA; Department of Human Genetics, Emory University, Atlanta, GA 30322, USA; Department of Pediatrics, Emory University, Atlanta, GA 30322, USA. Electronic address:

Lesch-Nyhan disease (LND) is an inherited metabolic disorder characterized by the overproduction of uric acid and distinct behavioral, cognitive, and motor abnormalities. The most challenging clinical problem is self-injurious behavior (SIB), which includes self-biting, self-hitting, self-abrasion, and other features. Currently, these behaviors are managed by behavioral extinction, sedatives, physical restraints, and removal of teeth. Read More

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http://dx.doi.org/10.1016/j.ymgme.2016.02.005DOI Listing
April 2016
4 Reads

The eye and the skin in nonendocrine metabolic disorders.

Clin Dermatol 2016 Mar-Apr;34(2):166-82. Epub 2015 Dec 7.

Department of Ophthalmology, Poznań City Hospital, ul. Szwajcarska 3, 61-285 Poznań, Poland; Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland. Electronic address:

As metabolism is controlled by the input of genes and the environment, metabolic disorders result from some disturbance in the interaction between genes and environmental factors. Many metabolic disorders consist in congenital enzyme deficiencies, also known as "inborn errors of metabolism," that may be disabling or cause severe illness and death and are predominantly inherited in an autosomal recessive fashion. The deposit in cells and tissues of storage substances from errors in metabolic processes may produce a wide variety of disorders affecting different organs and functions, with different degrees of severity, and often present around the time of birth or early childhood. Read More

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http://dx.doi.org/10.1016/j.clindermatol.2015.12.002DOI Listing
December 2016
9 Reads

An unusual case of renal failure: Answers.

Pediatr Nephrol 2017 01 11;32(1):79-80. Epub 2016 Jan 11.

Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1007/s00467-015-3300-6DOI Listing
January 2017
5 Reads

An unusual case of renal failure: Questions.

Pediatr Nephrol 2017 01 11;32(1):77-78. Epub 2016 Jan 11.

Department of Paediatric Nephrology, Great Ormond Street Hospital for Children NHS Foundation Trust, London, UK.

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http://dx.doi.org/10.1007/s00467-015-3288-yDOI Listing
January 2017
8 Reads

Altered histamine neurotransmission in HPRT-deficient mice.

Neurosci Lett 2015 Nov 19;609:74-80. Epub 2015 Oct 19.

Institute of Pharmacology, Hannover Medical School, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. Electronic address:

Lesch-Nyhan syndrome (LNS) is an X-chromosomal disorder with congenital deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as underlying defect. We determined the concentrations of dopamine, histamine and their metabolites in brains of HPRT knockout mice, which serve as an animal model for LNS, and compared the results to those obtained from wild-type controls. Analyses were performed by high performance liquid chromatography (HPLC)-coupled tandem mass spectrometry (MS/MS). Read More

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http://dx.doi.org/10.1016/j.neulet.2015.10.011DOI Listing
November 2015
4 Reads

Epigenetic Regulation in Amyloid Precursor Protein with Genomic Rearrangements and the Lesch-Nyhan Syndrome.

Authors:
Khue Vu Nguyen

Nucleosides Nucleotides Nucleic Acids 2015 23;34(10):674-90. Epub 2015 Sep 23.

a 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.

Recently, epigenetic regulation of alternative APP pre-mRNA splicing in the Lesch-Nyhan syndrome (LNS) has been studied (see Ref. 7) and showed for the first time, the presence of several APP-mRNA isoforms encoding divers APP protein isoforms ranging from 120 to 770 amino acids (with or without mutations and/or deletions). Here, by continuing on this work, I identified, for the first time new APP-mRNA isoforms with a deletion followed by an insertion (INDELS) in LNS and LNVs patients: c. Read More

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http://dx.doi.org/10.1080/15257770.2015.1071844DOI Listing
August 2016
2 Reads