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

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.

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

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.

Physiological levels of folic acid reveal purine alterations in Lesch-Nyhan disease.

Lesch-Nyhan disease (LND), caused by a deficient salvage purine pathway, is characterized by severe neurological manifestations and uric acid overproduction. However, uric acid is not responsible for brain dysfunction, and it has been suggested that purine nucleotide depletion, or accumulation of other toxic purine intermediates, could be more relevant. Here we show that purine alterations in LND fibroblasts depend on the level of folic acid in the culture media.

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

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.

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

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.

Animal Model Contributions to Congenital Metabolic Disease.

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.

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

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

Rescuing compounds for Lesch-Nyhan disease identified using stem cell-based phenotypic screening.

Lesch-Nyhan disease (LND) is a rare monogenic disease caused by deficiency of the salvage pathway enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). LND is characterized by severe neuropsychiatric symptoms that currently cannot be treated. Predictive in vivo models are lacking for screening and evaluating candidate drugs because LND-associated neurological symptoms are not recapitulated in HGPRT-deficient animals.

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

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.

Clinical outcome of prenatally suspected cardiac rhabdomyomas of the fetus.

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.

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

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.

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

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.

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

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.

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

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.

Positron Emission Tomography in Pediatric Neurodegenerative Disorders.

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.

Tongue Protrusion Dystonia in Pantothenate Kinase-Associated Neurodegeneration.

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.

Animal Models of Self-Injurious Behavior: An Update.

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.

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

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.

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

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.

Genetic mimics of cerebral palsy.

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.

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

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.