RARE DISEASE
Lesch-Nyhan syndrome
Lesch-Nyhan syndrome
Lesch-Nyhan syndrome
Synonyms: HPRT complete deficiency, HPRT deficiency grade IV, Hypoxanthine guanine phosphoribosyltransferase complete deficiency, Hypoxanthine guanine phosphoribosyltransferase deficiency, grade IV
Synonyms: HPRT complete deficiency, HPRT deficiency grade IV, Hypoxanthine guanine phosphoribosyltransferase complete deficiency, Hypoxanthine guanine phosphoribosyltransferase deficiency, grade IV
Synonyms: HPRT complete deficiency, HPRT deficiency grade IV, Hypoxanthine guanine phosphoribosyltransferase complete deficiency, Hypoxanthine guanine phosphoribosyltransferase deficiency, grade IV
Drug discovery
5
drugs
With orphan designations
Overview
Lesch-Nyhan syndrome is an X-linked recessive disorder caused by HPRT1 gene mutations, leading to deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT). This results in hyperuricemia, progressive neurological dysfunction (dystonia, choreoathetosis), and compulsive self-injurious behaviors. Renal complications (nephrolithiasis) and gout arise from uric acid overproduction, while dopaminergic dysfunction underlies neurobehavioral manifestations [1][2][6][10].
Categories: rare genetic diseases, rare hematological diseases, rare inborn errors of metabolism, rare neurological diseases, rare renal diseases, rare transplant-related disorders
Research Papers
256 drug discovery papers about Lesch-Nyhan syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
256 drug discovery papers about Lesch-Nyhan syndrome, with 2 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-07-13 | Bioinformatic analysis of gene networks and molecular pathways in Lesch-Nyhan Syndrome: A comprehensive enrichment study
Aim: Lesch–Nyhan syndrome (LNS) is a rare X-linked recessive disorder caused by hypoxanthine-guanine phosphoribosyl transferase deficiency, resulting in neurological dysfunction, cognitive impairment, and self-injurious behaviour. Despite longstanding clinical characterisation, molecular networks linking purine metabolism defects to systemic manifestations remain poorly understood. This study aimed to define the functional characteristics, pathway associations, transcriptional regulation, and tissue-specific expression patterns of LNS-associated genes. Methodology: Ten LNS-implicated genes retrieved from GeneCards were analysed via Enrichr. Gene Ontology (GO) 2025 characterised biological processes, molecular functions, and cellular components. Reactome 2024 identified pathway interactions, ChEA predicted transcription factor regulation, HMDB mapped metabolite associations, and GTEx assessed tissue-specific expression. A significance threshold of p < 0.05 was applied. Results: Enrichment analyses highlighted the key roles in purine metabolism, urate transport, dopamine regulation, and nucleotide biosynthesis. Implicated genes were associated with metabolic enzymes, neurotransmitter balance, and lipoprotein particle components. Transcription factor analysis identified regulatory elements governing gene expression, whilst tissue-specific patterns indicated neurological and metabolic involvement. Interpretation: This integrative analysis connects purine metabolic dysregulation with the complex neurological and systemic features of LNS, proposing potential molecular targets warranting further preclinical investigation for therapeutic development. Key words: Bioinformatics, Gene enrichment analysis, HPRT1 deficiency, Lesch-Nyhan syndrome, Purine metabolism
2026-05-01 | Learning and memory disorders in impaired striatum lack sufficient HGPRTI on exposure to caffeine and KBr03, whereas its chemotherapeutic treatment with naringenin-7-O-neohesperidoside was elicited via NOS/cAMP/PKA and BDNF/TrkB signaling responses
• Mixture of caffeine and KBrO 3 causes vasoconstriction injury. • It also promotes striatum limbic neurotransmitter enzymes. • It also exerts the symptoms of Lesch-Nyhan-Syndrome (LNS) • Naringenin-7-O-neohesperidoside inhibits vasoconstriction injury. • It depletes the indicators of LNS in an in-vivo model. This study investigated the chemotherapeutic efficacy of naringenin-7-O-neohesperidoside (NAR) against Lesch-Nyhan syndrome and neurobehavioral abnormalities in rat models. Ninety male Wistar rats were grouped into nine groups (n = 10). Group I: control rats, Group II was exposed to 100 mg/kg KBrO 3 , Group III was exposed to 250 mg/kg CAF, Group IV was exposed to 100 mg/kg KBrO 3 + 250 mg/kg CAF. Group V was administered with 100 mg/kg KBrO 3 + 100 mg/kg HAL. Group VI was administered with 100 mg/kg KBrO 3 + 50 mg/kg NAR. Group VII was administered with 250 mg/kg CAF + 50 mg/kg NAR. Group VIII was treated with 100 mg/kg KBrO 3 + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The study lasted for five weeks. The result showed that striatal hypoxanthine–guanine-phosphoribosyl transferase-1 (HGPRT1) was suppressed on exposure to KBrO 3 only, CAF only and KBrO 3 + CAF by 52.5% when compared with the control. The post-administration with NAR remarkably elevated the expression of striatal HGPRT1 in relation to the corresponding exposed groups by 22.8%, 31.6%, 40.4% and 14.0%, respectively. NAR also inhibited the activities of arginase and phosphodiesterase-5 1 (PDE-5 1 ) with corresponding up-regulation of dopamine and cAMP-regulated-phosphoprotein (DARPP), brain-derived neurotrophic factor (BDNF), and tropomyosin-receptor-kinase-B (TrkB). Similarly, the gene coding for B-cell lymphoma/leukaemia 11b (Bcl11b) was down-regulated. Additionally, NAR remarkably reduced the activities of AChE, BuChE, MAO-A and enzymes of ATP hydrolysis (ATPase, AMPase and ADA) with consequential increase in NO level. Also, locomotion, coordination, and memory were improved upon post-treatment with NAR, followed by repression of self-mutilation, anxiety and depression. Also, vascular congestion of nigrostriatal tracts, cellular degeneration of striatum, plasma uric-acid and malonaldehyde (MDA) contents were essentially lowered. This study proposes that NAR could be a viable therapeutic agent for the up-regulation of striatal-HGPRTI-gene to inhibit Lesch-Nyhan Syndrome and neurobehavioral abnormalities through NOS/cAMP/PKA and BDNF/TrkB signalling cascades in a rat model
2026-01-17 | Conservative management of oral self-mutilation in Lesch–Nyhan syndrome enhanced by a digital workflow: a case report
Abstract Introduction Lesch-Nyhan Syndrome (LNS) is a rare X-linked disorder characterized by the triad of hyperuricemia, neurological dysfunction, and compulsive self-injurious behavior, often involving oral self-mutilation. Objective This report describes the conservative, multidisciplinary management of severe oral self-mutilation in a hospitalized child with LNS, combining botulinum toxin and a digitally fabricated customized bite plate. Case Report A 10-year-old male with LNS was admitted to the Intensive Care Unit due to gastrostomy-related perforation and sepsis. Oral examination revealed complete permanent dentition, generalized dental calculus and gingivitis, cicatricial lesions on the tongue, and partial loss of the lower lip due to chronic self-biting. Previous provisional bite plates had proven ineffective. Methods The patient underwent periodontal treatment, botulinum toxin application to the bilateral masseter and orbicularis oris muscles, and placement of a customized bite plate fabricated via digital intraoral scanning and 3D printing. Patients with additional neurological conditions might potentially benefit from it. Results Post-intervention, parafunctional movements decreased, soft tissue lesions partially healed, and oral function was preserved without adverse effects. Conclusion This case report reveals that combining tailored care, botulinum toxin therapy, and digital splint manufacture creates a realistic and patient-centered alternative to extreme interventions, preserving oral function and contributing to enhanced quality of life.
2025-12-22 | Understanding Lesch-Nyhan Syndrome: Overview and Pharmacotherapeutic Strategies
Lesch-Nyhan Syndrome is a rare genetic disorder related to chromosome X and characterized by a mutation in the HGPRT1 gene. This mutation leads to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). The lack of HGPRT results in the accumulation of uric acid in all body fluids, which in turn causes severe neurological and behavioral symptoms.Self-mutilating behavior, characterized by lip and finger biting, is a hallmark feature of this syndrome. High uric acid levels result in the accumulation of sodium urate crystals in joints, kidneys, the Central Nervous System, and other parts of the body, resulting in swelling of the joints, severe kidney problems, and neurological features. Symptom control is the mainstay of the treatment. Allopurinol can prevent excessive amounts of uric acid accumulation in joints. Kidney stones in Lesch-Nyhan 102Syndrome can be treated with lithotripsy, while physiotherapy is recommended to prevent contractures. However, no standard treatment currently exists to address the neurological symptoms of Lesh-Nyhan Syndrome. A variety of patients can benefit from drugs like diazepam, phenobarbital, haloperidol, levodopa, or carbidopa. Further research into more options, such as targeted gene therapy for the definitive management of the condition, is required to develop a standard treatment.
2025-12-19 | Umbilical Cord Blood Transplantation in Lesch-Nyhan Syndrome: A Case Report and Literature Review.
Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene mutations, leading to HPRT1 deficiency, hyperuricemia, and severe neurological dysfunction, including self-injurious behavior. Hematopoietic stem cell transplantation (HSCT) has been applied to some inborn errors of metabolism (IEM), yet only a few cases with limited success in LNS have been reported. This case was diagnosed with LNS at nine months of age due to developmental delays. He subsequently received 5/6 human leukocyte antigen-matched umbilical cord blood transplantation (UCBT) at 14 months of age. Myeloablative conditioning included fludarabine, busulfan, and antithymocyte globulin. This patient achieved complete donor chimerism on day 32 after UCBT. Before UCBT, the patient's HPRT1 protein was lower than his parents, but the levels increased after UCBT. At 36 months of age, no self-mutilation was noted, and neurological improvement was found. HSCT is more effective in preventing disease progression in IEM than in reversing established manifestations, making early diagnosis critical. In this case, LNS was diagnosed early, allowing prompt HSCT. To our knowledge, this is the youngest LNS patient to receive HSCT. We propose that early HSCT may contribute to neurological improvements. Early UCBT is feasible and may prevent self-mutilation and promote neurological recovery in LNS. Further studies are needed.
2026-07-13 | Bioinformatic analysis of gene networks and molecular pathways in Lesch-Nyhan Syndrome: A comprehensive enrichment study
Aim: Lesch–Nyhan syndrome (LNS) is a rare X-linked recessive disorder caused by hypoxanthine-guanine phosphoribosyl transferase deficiency, resulting in neurological dysfunction, cognitive impairment, and self-injurious behaviour. Despite longstanding clinical characterisation, molecular networks linking purine metabolism defects to systemic manifestations remain poorly understood. This study aimed to define the functional characteristics, pathway associations, transcriptional regulation, and tissue-specific expression patterns of LNS-associated genes. Methodology: Ten LNS-implicated genes retrieved from GeneCards were analysed via Enrichr. Gene Ontology (GO) 2025 characterised biological processes, molecular functions, and cellular components. Reactome 2024 identified pathway interactions, ChEA predicted transcription factor regulation, HMDB mapped metabolite associations, and GTEx assessed tissue-specific expression. A significance threshold of p < 0.05 was applied. Results: Enrichment analyses highlighted the key roles in purine metabolism, urate transport, dopamine regulation, and nucleotide biosynthesis. Implicated genes were associated with metabolic enzymes, neurotransmitter balance, and lipoprotein particle components. Transcription factor analysis identified regulatory elements governing gene expression, whilst tissue-specific patterns indicated neurological and metabolic involvement. Interpretation: This integrative analysis connects purine metabolic dysregulation with the complex neurological and systemic features of LNS, proposing potential molecular targets warranting further preclinical investigation for therapeutic development. Key words: Bioinformatics, Gene enrichment analysis, HPRT1 deficiency, Lesch-Nyhan syndrome, Purine metabolism
2026-05-01 | Learning and memory disorders in impaired striatum lack sufficient HGPRTI on exposure to caffeine and KBr03, whereas its chemotherapeutic treatment with naringenin-7-O-neohesperidoside was elicited via NOS/cAMP/PKA and BDNF/TrkB signaling responses
• Mixture of caffeine and KBrO 3 causes vasoconstriction injury. • It also promotes striatum limbic neurotransmitter enzymes. • It also exerts the symptoms of Lesch-Nyhan-Syndrome (LNS) • Naringenin-7-O-neohesperidoside inhibits vasoconstriction injury. • It depletes the indicators of LNS in an in-vivo model. This study investigated the chemotherapeutic efficacy of naringenin-7-O-neohesperidoside (NAR) against Lesch-Nyhan syndrome and neurobehavioral abnormalities in rat models. Ninety male Wistar rats were grouped into nine groups (n = 10). Group I: control rats, Group II was exposed to 100 mg/kg KBrO 3 , Group III was exposed to 250 mg/kg CAF, Group IV was exposed to 100 mg/kg KBrO 3 + 250 mg/kg CAF. Group V was administered with 100 mg/kg KBrO 3 + 100 mg/kg HAL. Group VI was administered with 100 mg/kg KBrO 3 + 50 mg/kg NAR. Group VII was administered with 250 mg/kg CAF + 50 mg/kg NAR. Group VIII was treated with 100 mg/kg KBrO 3 + 250 mg/kg CAF + 50 mg/kg NAR. Finally, group IX was treated with 50 mg/kg NAR. The study lasted for five weeks. The result showed that striatal hypoxanthine–guanine-phosphoribosyl transferase-1 (HGPRT1) was suppressed on exposure to KBrO 3 only, CAF only and KBrO 3 + CAF by 52.5% when compared with the control. The post-administration with NAR remarkably elevated the expression of striatal HGPRT1 in relation to the corresponding exposed groups by 22.8%, 31.6%, 40.4% and 14.0%, respectively. NAR also inhibited the activities of arginase and phosphodiesterase-5 1 (PDE-5 1 ) with corresponding up-regulation of dopamine and cAMP-regulated-phosphoprotein (DARPP), brain-derived neurotrophic factor (BDNF), and tropomyosin-receptor-kinase-B (TrkB). Similarly, the gene coding for B-cell lymphoma/leukaemia 11b (Bcl11b) was down-regulated. Additionally, NAR remarkably reduced the activities of AChE, BuChE, MAO-A and enzymes of ATP hydrolysis (ATPase, AMPase and ADA) with consequential increase in NO level. Also, locomotion, coordination, and memory were improved upon post-treatment with NAR, followed by repression of self-mutilation, anxiety and depression. Also, vascular congestion of nigrostriatal tracts, cellular degeneration of striatum, plasma uric-acid and malonaldehyde (MDA) contents were essentially lowered. This study proposes that NAR could be a viable therapeutic agent for the up-regulation of striatal-HGPRTI-gene to inhibit Lesch-Nyhan Syndrome and neurobehavioral abnormalities through NOS/cAMP/PKA and BDNF/TrkB signalling cascades in a rat model
2026-01-17 | Conservative management of oral self-mutilation in Lesch–Nyhan syndrome enhanced by a digital workflow: a case report
Abstract Introduction Lesch-Nyhan Syndrome (LNS) is a rare X-linked disorder characterized by the triad of hyperuricemia, neurological dysfunction, and compulsive self-injurious behavior, often involving oral self-mutilation. Objective This report describes the conservative, multidisciplinary management of severe oral self-mutilation in a hospitalized child with LNS, combining botulinum toxin and a digitally fabricated customized bite plate. Case Report A 10-year-old male with LNS was admitted to the Intensive Care Unit due to gastrostomy-related perforation and sepsis. Oral examination revealed complete permanent dentition, generalized dental calculus and gingivitis, cicatricial lesions on the tongue, and partial loss of the lower lip due to chronic self-biting. Previous provisional bite plates had proven ineffective. Methods The patient underwent periodontal treatment, botulinum toxin application to the bilateral masseter and orbicularis oris muscles, and placement of a customized bite plate fabricated via digital intraoral scanning and 3D printing. Patients with additional neurological conditions might potentially benefit from it. Results Post-intervention, parafunctional movements decreased, soft tissue lesions partially healed, and oral function was preserved without adverse effects. Conclusion This case report reveals that combining tailored care, botulinum toxin therapy, and digital splint manufacture creates a realistic and patient-centered alternative to extreme interventions, preserving oral function and contributing to enhanced quality of life.
2025-12-22 | Understanding Lesch-Nyhan Syndrome: Overview and Pharmacotherapeutic Strategies
Lesch-Nyhan Syndrome is a rare genetic disorder related to chromosome X and characterized by a mutation in the HGPRT1 gene. This mutation leads to a deficiency of the enzyme hypoxanthine-guanine phosphoribosyl transferase (HGPRT). The lack of HGPRT results in the accumulation of uric acid in all body fluids, which in turn causes severe neurological and behavioral symptoms.Self-mutilating behavior, characterized by lip and finger biting, is a hallmark feature of this syndrome. High uric acid levels result in the accumulation of sodium urate crystals in joints, kidneys, the Central Nervous System, and other parts of the body, resulting in swelling of the joints, severe kidney problems, and neurological features. Symptom control is the mainstay of the treatment. Allopurinol can prevent excessive amounts of uric acid accumulation in joints. Kidney stones in Lesch-Nyhan 102Syndrome can be treated with lithotripsy, while physiotherapy is recommended to prevent contractures. However, no standard treatment currently exists to address the neurological symptoms of Lesh-Nyhan Syndrome. A variety of patients can benefit from drugs like diazepam, phenobarbital, haloperidol, levodopa, or carbidopa. Further research into more options, such as targeted gene therapy for the definitive management of the condition, is required to develop a standard treatment.
2025-12-19 | Umbilical Cord Blood Transplantation in Lesch-Nyhan Syndrome: A Case Report and Literature Review.
Lesch-Nyhan syndrome (LNS) is a rare X-linked disorder caused by hypoxanthine phosphoribosyltransferase 1 (HPRT1) gene mutations, leading to HPRT1 deficiency, hyperuricemia, and severe neurological dysfunction, including self-injurious behavior. Hematopoietic stem cell transplantation (HSCT) has been applied to some inborn errors of metabolism (IEM), yet only a few cases with limited success in LNS have been reported. This case was diagnosed with LNS at nine months of age due to developmental delays. He subsequently received 5/6 human leukocyte antigen-matched umbilical cord blood transplantation (UCBT) at 14 months of age. Myeloablative conditioning included fludarabine, busulfan, and antithymocyte globulin. This patient achieved complete donor chimerism on day 32 after UCBT. Before UCBT, the patient's HPRT1 protein was lower than his parents, but the levels increased after UCBT. At 36 months of age, no self-mutilation was noted, and neurological improvement was found. HSCT is more effective in preventing disease progression in IEM than in reversing established manifestations, making early diagnosis critical. In this case, LNS was diagnosed early, allowing prompt HSCT. To our knowledge, this is the youngest LNS patient to receive HSCT. We propose that early HSCT may contribute to neurological improvements. Early UCBT is feasible and may prevent self-mutilation and promote neurological recovery in LNS. Further studies are needed.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
5 orphan drug designations for Lesch-Nyhan syndrome.
5 orphan drug designations for Lesch-Nyhan syndrome.
Drug | Therapy type | Regulator | Orphan designation | Approval | Sponsor |
|---|---|---|---|---|---|
6-fluoro-(18F)-L-3,4-dihydroxyphenylalanine | small molecules | FDA | 2016-09-07 | — | Advanced Imaging Projects, LLC |
Ecopipam | small molecules | EMA | 2010-02-03 | — | Dr Alain Munoz |
pegsitacase | proteins | FDA | 2009-12-03 | — | Swedish Orphan Biovitrum AB |
ecopipam hydrochloride | small molecules | FDA | 2009-07-21 | — | Emalex Biosciences, Inc. |
pramipexole | — | FDA | 2008-01-31 | — | Boehringer-Ingelheim Pharmaceuticals, Inc. |
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