Search Results (6)

Background: Lesch–Nyhan syndrome (LNS) is a rare X-linked recessive metabolic disorder caused by mutations in the HPRT1 gene, resulting in hypoxanthine–guanine phosphoribosyltransferase (HPRT) deficiency. Early diagnosis is critical for optimizing management and improving outcomes. This study presents a case series of three Taiwanese patients diagnosed at a single medical center. Methods: Exome sequencing and biochemical testing were used to confirm the diagnoses. Early clinical manifestations, including hyperuricemia, hypotonia, and developmental delay, were documented during the initial stages of the disease. Results: All three patients had hyperuricemia, hypotonia, spasticity, and motor developmental delay. Pathogenic variants in the HPRT1 gene were identified in two patients, while the third was confirmed by biochemical testing. Two patients had orange-colored crystalline deposits in their diapers, indicative of hyperuricosuria. Self-injurious behavior had not yet developed in two patients due to their young age. Conclusions: Early clinical features such as hyperuricemia, hypotonia, and motor delay may suggest LNS in infancy. Molecular genetic testing, particularly whole exome sequencing, can facilitate an early diagnosis before specific manifestations occur, enabling timely interventions and improving patient outcomes. Full article

Lesch–Nyhan syndrome (LN) is an is an X-linked recessive inborn error of metabolism that arises from a deficiency of purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). The disease manifests severely, causing intellectual deficits and other neural abnormalities, hypercoagulability, uncontrolled self-injury, and gout. While allopurinol is used to alleviate gout, other symptoms are less understood, impeding treatment. Herein, we present a high-throughput multi-omics analysis of red blood cells (RBCs) from three pediatric siblings carrying a novel S162N HPRT1 mutation. RBCs from both parents—the mother, a heterozygous carrier, and the father, a clinically healthy control—were also analyzed. Global metabolite analysis of LN RBCs shows accumulation of glycolytic intermediates upstream of pyruvate kinase, unsaturated fatty acids, and long chain acylcarnitines. Similarly, highly unsaturated phosphatidylcholines are also elevated in LN RBCs, while free choline is decreased. Intracellular iron, zinc, selenium, and potassium are also decreased in LN RBCs. Global proteomics documented changes in RBC membrane proteins, hemoglobin, redox homeostasis proteins, and the enrichment of coagulation proteins. These changes were accompanied by elevation in protein glutamine deamidation and methylation in the LN children and carrier mother. Treatment with allopurinol incompletely reversed the observed phenotypes in the two older siblings currently on this treatment. This unique data set provides novel opportunities for investigations aimed at potential therapies for LN-associated sequelae. Full article

Lesch–Nyhan syndrome (LNS) is a rare genetic condition resulting from an inherited disorder of purine metabolism. It is characterized by the lack of one enzyme, hypoxanthine-guanine phos-phoribosyltransferase (HGPRT), which is responsible for purine salvage. The main manifestations of this syndrome are hyperuricaemia, reduction in cognitive abilities, self-aggressive behavior, choreoathetosis, spasticity, and retarded development. The aim of the study was to investigate the means of treatment and efficacy of prevention of oral self-injury behavior (SIB) in patients with LNS. Information regarding the type and treatment of oral SIB in 19 LSN Italian patients (mean age 23.3 years) was gathered via a structured telephone interview of their parents. A total of 84% of the patients showed some form of self-injury behavior; the first form to manifest itself was finger biting (37%), followed by lip biting (25%), and then tongue biting (18%). Furthermore, 74% of cases featured oral SIB, and tooth extraction was found to be the most frequent form of treatment practiced (71%). This study has revealed the great difficulty parents and carers face in managing forms of oral SIB; dental extraction was the most common choice, despite its invasive nature and far-reaching consequences in regard to the psychosocial status of the patients. Full article

Lesch-Nyhan syndrome (LNS) is a serious form of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, a hereditary purine metabolism disorder. The prevalence reported in the literature is 1/380,000 to 235,000 births. Males are affected and females are heterozygous carriers. LNS patients present a combination of hypotonia, spasticity, and neurological and behavioral disorders. They also show an obsessive-compulsive self-injurious behavior with bites and injuries to the lips, tongue, cheeks and fingers. The literature offers little scientific contribution related to the management of this problem. The authors describe their experience with a 4-year-old LNS patient and present a viable solution to control and avoid bite injuries, namely a specifically modified bite. The patient was treated at the Pediatric Dentistry Department of “Sapienza” University of Rome with a modified bite with the internal surface, in contact with the teeth, realized in 2-mm-thick soft silicone, and the exterior part consisting of a transparent resin shell with front and rear shields to separate lips and cheeks from the dental arches. At a 12-month follow-up visit, compliance was excellent: the child wore the device with regularity and without discomfort, even during soft-food feeding. No intraoral bite injuries were found, with a general improvement of the young patient’s quality of life. Full article

Lesch–Nyhan syndrome (LNS) is a rare X-linked recessive disorder with an incidence of 1/100,000–380,000 live births. It is characterized by neurological manifestations, including symptoms of compulsive self-mutilation, which result in the destruction of oral and perioral tissues. This report describes a case of a four-year-old boy diagnosed with LNS, who was referred for evaluation and treatment of self-injury behaviour (SIB). The parents requested the prevention of self-mutilation of the lower lip and tongue by the child’s own teeth. After a thorough discussion with the parents, it was agreed that a conservative approach, avoiding extraction, should be followed initially. A removable dental appliance was fabricated. The parents were instructed and trained about insertion, removal, and cleaning of the appliance. The child was re-examined after one week: biting of the lips and tongue improved immediately after the insertion of the appliances. Initial healing of the lesion was observed. After two and four weeks, positive results were seen. The lesion had resolved completely. In conclusion, appropriate preventive methods have to be developed for each individual patient on the basis of the observation of each single case. Oral appliances represent a conservative solution for SIB and an alternative to more invasive approaches. They can be the initial solution for the management of oral self-injury in LNS patients. Full article

Nucleotide balance is critically important not only in replicating cells but also in quiescent cells. This is especially true in the nervous system, where there is a high demand for adenosine triphosphate (ATP) produced from mitochondria. Mitochondria are particularly prone to oxidative stress-associated DNA damage because nucleotide imbalance can lead to mitochondrial depletion due to low replication fidelity. Failure to maintain nucleotide balance due to genetic defects can result in infantile death; however there is great variability in clinical presentation for particular diseases. This review compares genetic diseases that result from defects in specific nucleotide salvage enzymes and a signaling kinase that activates nucleotide salvage after DNA damage exposure. These diseases include Lesch-Nyhan syndrome, mitochondrial depletion syndromes, and ataxia telangiectasia. Although treatment options are available to palliate symptoms of these diseases, there is no cure. The conclusions drawn from this review include the critical role of guanine nucleotides in preventing neurodegeneration, the limitations of animals as disease models, and the need to further understand nucleotide imbalances in treatment regimens. Such knowledge will hopefully guide future studies into clinical therapies for genetic diseases. Full article