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Lesch Nyhan

Shimpei Baba, Takashi Saito, Yasukazu Yamada, Eri Takeshita, Noriko Nomura, Kenichiro Yamada, Nobuaki Wakamatsu, Masayuki Sasaki
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. He showed developmental delay, athetosis, and dystonic posture from early infancy, but no self-injurious behaviors. Hyperuricemia was detected, and his HPRT enzyme activity in erythrocytes was completely deficient...
October 18, 2016: Nucleosides, Nucleotides & Nucleic Acids
E Stur, R S Reis, L P Agostini, A M A Silva-Conforti, I D Louro
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. In 1989, Fujimori et al. reported on a patient diagnosed with LNS who had an HPRT variant thereafter codenamed HPRTYale...
2016: Genetics and Molecular Research: GMR
Khue Vu Nguyen, William L Nyhan
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.L146S. Molecular diagnosis discloses the genetic heterogeneity of the HPRT1 gene responsible for HGprt deficiency...
August 2, 2016: Nucleosides, Nucleotides & Nucleic Acids
Prasad Jathar, Amey M Panse, Madhura Jathar, Pritesh N Gawali
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. A case of a 10-month-old boy with aggressive behavior and severe lower lip injuries is presented. How to cite this article: Jathar P, Panse AM, Jathar M, Gawali PN...
April 2016: International Journal of Clinical Pediatric Dentistry
Matthias Lauber, Barbara Plecko, Miriam Pfiffner, Jean-Marc Nuoffer, Johannes Häberle
BACKGROUND: Lesch-Nyhan disease (LND) is an X-chromosomal disorder of purine metabolism characterized by hyperuricemia, dystonia, and self-mutilation, leading to an extremely high burden of disease in affected patients and families. Although allopurinol therapy can control hyperuricemia, it has no effect on self-mutilation and neurological symptoms. Single reports describe a beneficial effect of S-adenosylmethionine (SAM) on the neurological symptoms, which motivated us to evaluate this alternative treatment...
June 14, 2016: JIMD Reports
Sarah K Tschirner, Heike Bähre, Alexander Kaever, Erich H Schneider, Roland Seifert, Volkhard Kaever
AIMS: Lesch-Nyhan disease (LND) is characterized by hyperuricemia as well as neurological and neuropsychiatric symptoms including repetitive self-injurious behavior. Symptoms are caused by a deficiency of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) as a result of a mutation on the X chromosome. To elucidate the pathophysiology of LND, we performed a metabolite screening for brain and serum extracts from HPRT knockout mice as an animal model for LND. MAIN METHODS: Analyses were performed by high performance liquid chromatography (HPLC)-coupled quadrupole time-of-flight mass spectrometry (QTOF-MS)...
July 1, 2016: Life Sciences
Roland Seifert
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. (Mol. Genetic. Metab., in press) on drug treatment of SIB into a broader context. Although the study by Khasnavis et al. was no break-through in terms of "positive" results, nonetheless, it presents an excellent model of how clinical studies in general and clinical studies on rare diseases should be conducted...
July 2016: Molecular Genetics and Metabolism
Sarah K Tschirner, Frank Gutzki, Erich H Schneider, Roland Seifert, Volkhard Kaever
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)...
June 15, 2016: Journal of the Neurological Sciences
Julia Thumfart, Bernhard Weschke, Hannelore Ringe, Natalie Weinhold, Dominik Müller
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. Due to the inappropriate high levels of uric acid compared to kidney function, screening of hypoxanthine-guanine phosphoribosyltransferase (HPRT) related diseases was initiated...
July 2016: European Journal of Paediatric Neurology: EJPN
Stephen Meek, Alison J Thomson, Linda Sutherland, Matthew G F Sharp, Julie Thomson, Valerie Bishop, Simone L Meddle, Yoann Gloaguen, Stefan Weidt, Karamjit Singh-Dolt, Mia Buehr, Helen K Brown, Andrew C Gill, Tom Burdon
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...
2016: Scientific Reports
Tanya Khasnavis, Rosa J Torres, Barbara Sommerfeld, Juan Garcia Puig, Richard Chipkin, H A Jinnah
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. Current treatments for SIB involve behavioral extinction, sedatives, physical restraints, and removal of teeth...
July 2016: Molecular Genetics and Metabolism
E Vargiami, N Printza, E Papadimiditriou, S Batzios, M Kyriazi, F Papachristou, D I Zafeiriou
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 HRPT 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...
April 11, 2016: Urology
Darin J Knapp, George R Breese
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...
2016: Current Topics in Behavioral Neurosciences
Helena Biasibetti, Paula Pierozan, André Felipe Rodrigues, Vanusa Manfredini, Angela T S Wyse
Hypoxanthine, the major oxypurine metabolite involved in purine's salvage pathway in the brain, is accumulated in Lesch-Nyhan disease, an inborn error of metabolism of purine. The purpose of this study was to investigate the effects of hypoxanthine intrastriatal administration on infant and young adult rats submitted to stereotactic surgery. We analyzed the effect of hypoxanthine on neuroinflammatory parameters, such as cytokine levels, immunocontent of NF-κB/p65 subunit, iNOS immunocontent, nitrite levels, as well as IBA1 and GFAP immunocontent in striatum of infant and young adult rats...
March 24, 2016: Molecular Neurobiology
Tanya Khasnavis, Gail Reiner, Barbara Sommerfeld, William L Nyhan, Richard Chipkin, H A Jinnah
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. More effective treatments are needed. Pre-clinical studies have led to the hypothesis that D1-dopamine receptor antagonists may provide useful treatments for SIB in LND...
April 2016: Molecular Genetics and Metabolism
W Harth
Self-injury often occurs for the first time in adolescence. The current classification distinguishes several groups: (1) factitious disorder imposed on self and factitious disorder imposed on another, (2) nonsuicidal self-injury (NSSI) and (3) obsessive-compulsive (OCD) and related disorders. The differential diagnosis includes a wide spectrum of psychiatric diseases, including borderline personality disorder (BPD), inherited disorders like Lesch-Nyhan syndrome (LNS) and also body modifications. In all these cases, self-harm is a subphenomenon...
April 2016: Der Hautarzt; Zeitschrift Für Dermatologie, Venerologie, und Verwandte Gebiete
Qin Sun
Inborn errors of purine metabolism, either deficiencies of synthesis or catabolism pathways, lead to a wide spectrum of clinical presentations: urolithiasis (adenine phosphoribosyltransferase), primary immune deficiency (adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency), severe intellectual disability, and other neurological symptoms (Lesch-Nyhan disease, adenylosuccinase deficiency, and molybdenum cofactor deficiency). A rapid quantitative purine assay was developed using UPLC-MS/MS to determine purine nucleoside and base concentrations in urine...
2016: Methods in Molecular Biology
Sarah K Tschirner, Frank Gutzki, Volkhard Kaever, Roland Seifert, Erich H Schneider
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)...
November 16, 2015: Neuroscience Letters
Khue Vu Nguyen
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.19_2295delinsG166TT…GAGTCC…CTTAGTC…TCT489,p...
2015: Nucleosides, Nucleotides & Nucleic Acids
Ghiabe-Henri Guibinga
MicroRNAs (miRNAs) are small regulatory RNAs that modulate the translation of mRNA. They have emerged over the past few years as indispensable entities in the transcriptional regulation of genes. Their discovery has added additional layers of complexity to regulatory networks that control cellular homeostasis. Also, their dysregulated pattern of expression is now well demonstrated in myriad diseases and pathogenic processes. In the current review, we highlight the role of miRNAs in Lesch-Nyhan disease (LND), a rare neurogenetic syndrome caused by mutations in the purine metabolic gene encoding the hypoxanthine-guanine phosphoribosyltransferase (HPRT) enzyme...
2015: Advances in Genetics
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