Disorder Of Uric Acid Metabolism Research Articles

Metabolic syndrome and hyperuricemia: features of patient management (clinical case)

Metabolic syndrome (MS) is a group of interrelated metabolic disorders such as high blood pressure, central obesity, insulin resistance (IR), dyslipidemia. The main mechanisms that indicate a metabolic disorder and contribute to its development are IR and a large amount of circulating free fatty acids. In turn, tissue IR is often combined with other abnormalities including disorders of uric acid metabolism, changes in the hemostasis system, endothelial dysfunction, increased levels of C-reactive protein. At the same time, metabo­lic disorders are a risk factor for hyperuricemia. MS occurs in 25–60 to 90 % of all gout patients. About 50 % of patients with hyperuricemia have symptoms of MS. Hyperuricemia as a component of MS is a predictor of cardiovascular mortality, development of diabetes mellitus, hypertension and nephrolithiasis. Hyperuricemia is closely related to diabetes, obesity, coronary heart disease, hypertension. On the example of a clinical case, the main components of MS are considered, as well as the issue of the relationship between hyperuricemia, gout and the components of MS. The main idea behind the creation of the MS concept is to select a population of patients at a high cardiovascular risk in whom preventive measures such as lifestyle modification and the use of adequate drugs can significantly affect the main health indicators. The goal of managing patients with MS is to minimize cardiovascular risk and mortality as much as possible. Accordingly, the therapeutic strategy should include optimal ways to modify the lifestyle; lowering blood pressure to the target level and treating comorbid conditions; reducing low-density lipoprotein cholesterol according to the risk profile: > 50 %, and < 70 mg/dL (1.4 mmol/L) in patients at a very high cardiovascular risk; > 50 %, and < 100 mg/dL (1.8 mmol/l) in high-risk patients; reducing fasting serum glucose < 126 mg/dl (7 mmol/l) or glycated hemoglobin < 7 % (53 mmol/mol); maintaining uric acid level < 6.5 mg/dL (0.387 mmol/L), in patients with gout — below 6 mg/dL (0.357 mmol/L). Thus, according to the results of the research, a causal relationship was found between insulin resistance and serum uric acid levels in patients with metabolic syndrome. The strategy for managing patients with metabolic syndrome should include screening and correction of hypertension, carbohydrate purine metabolism, dyslipidemia, and prevention of cardiovascular events.

Anti-hyperuricemia bioactive peptides: a review on obtaining, activity, and mechanism of action.

Hyperuricemia, a disorder of uric acid metabolism, serves as a significant risk factor for conditions such as hypertension, diabetes mellitus, renal failure, and various metabolic syndromes. The main contributors to hyperuricemia include overproduction of uric acid in the liver or impaired excretion in the kidneys. Despite traditional clinical drugs being employed for its treatment, significant health concerns persist. Recently, there has been growing interest in utilizing protein peptides sourced from diverse food origins to mitigate hyperuricemia. This article provides a comprehensive review of bioactive peptides with anti-hyperuricemia properties derived from animals, plants, and their products. We specifically outline the methods for preparing these peptides from food proteins and elucidate their efficacy and mechanisms in combating hyperuricemia, supported by in vitro and in vivo evidence. Uric acid-lowering peptides offer promising prospects due to their safer profile, enhanced efficacy, and improved bioavailability. Therefore, this review underscores significant advancements and contributions in identifying peptides capable of metabolizing purine and/or uric acid, thereby alleviating hyperuricemia. Moreover, it offers a theoretical foundation for the development of functional foods incorporating uric acid-lowering peptides.

Potential of Leave and Fruit Ethanolic Extract of Etlingera hemisphaerica as Antihyperuricemic in Mice (Mus musculus).

<b>Background and Objective:</b> Hyperuricemia is a disease triggered by disorders of uric acid metabolism. Therefore, this study evaluated the potential of leaves ethanolic extract of <i>Etlingera hemisphaerica</i> (LE3H) and fruits ethanolic extract <i>E. hemisphaerica</i> (FE3H) to restore hyperuricemia in mice. <b>Materials and Methods:</b> Six groups (A0, A1, A2, A3, A4 and A5) each consisted of four male mice. Hyperuricemia in mice was induced by giving 0.3 mL of fresh chicken liver juice (FCLJ) for seven days (A1, A2, A3, A4 and A5). The condition of hyperuricemia in A1 is not neutralized. Meanwhile, hyperuricemia conditions in A2, A3, A4 and A5 were neutralized for seven days by giving 0.01 mg g<sup></sup><sup>1</sup> body weight (BW) allopurinol, 0.13, 0.26 and 0.36 mg g<sup></sup><sup>1</sup> BW LE3H. The control group (A0) only received double-distilled water in the same way. Blood uric acid levels were measured with the GCU Meter Device before and after the induction of hyperuricemia and after efforts to neutralize the hyperuricemia condition. Six groups (B0, B1, B2, B3, B4, B5) each consisting of four male mice were also provided to test the potential of FE3H. The recovery potential FE3H against hyperuricemia was tested separately in the same way as was done for LE3H. <b>Results:</b> Giving FCLJ significantly increased (140.00-187.00%) uric acid compared to the control, so hyperuricemia was achieved. Doses of 0.13, 0.26 and 0.36 mg g<sup></sup><sup>1</sup> BW LE3H significantly recovered hyperuricemia as much as 54.09, 56.14 and 60.88%, respectively. Meanwhile, doses of 0.13, 0.26 and 0.36 mg g<sup></sup><sup>1</sup> FE3H significantly recovered hyperuricemia as much as 60.37, 62.24 and 65.572%, respectively. The LE3H and FE3H at the same dose showed that FE3H had a higher potential to restore hyperuricemia than LE3H. <b>Conclusion:</b> Leave and fruit ethanolic extract of <i>E. hemisphaerica</i> can potentially restore hyperuricemia in mice.

Role of microRNA alternation in the pathogenesis of gouty arthritis.

Gouty arthritis is a common inflammatory disease. The condition is triggered by a disorder of uric acid metabolism, which causes urate deposition and gout flares. MicroRNAs are a class of conserved small non-coding RNAs that bind to the 3’ untranslated region (UTR) of mRNA and regulate the expression of a variety of proteins at the post-transcriptional level. In recent years, attention has been focused on the role of miRNAs in various inflammatory diseases, including gouty arthritis. It is thought that miRNAs may regulate immune function and inflammatory responses, thereby influencing the onset and progression of the disease. This article mainly reviewed the roles of miRNAs in the pathogenesis of gouty arthritis and prospected their potential as diagnostic and prognostic relevant biomarkers and as possible therapeutic targets.

Features of disorders of uric acid metabolism in male patients with hypertension and atrial fibrillation

Abstract Background In recent decades, a significant number of epidemiological studies showed the association between asymptomatic hyperuricemia and development of arterial hypertension (HTN) and atrial fibrillation (AF). The key enzyme participating in disintegration purines to uric acid is xanthine oxidase (XO). The accumulated data suggest the existence of a direct pathophysiological role of increased level of serum uric acid (SUA) and XO activity with a risk of HTN and AF. Purpose To evaluate the features of disorders of UA metabolism in patients with HTN and AF. Materials and methods The study included male patients 27 to 65 years, with a body mass index (BMI) less than 30 kg/m2 and more than 18.5 kg/m2. All patients were investigated of the level of a SUA, hypoxanthine/xanthine, inosine/adenosine, XO enzyme activity. Depending on the presence of AF, all patients were divided into 2 groups: group 1 (n=16) patients with HTN, group 2 (n=16) patients with HTN and AF. Results Table 1 shows the indicators of purine metabolism in the compared groups. The analysis of the results demonstrates that in group 1 the smallest level of a SUA in comparison with group 2 (0.35 [0.31; 0.41] vs 0.41 [0.39; 0.40](μmol/l), p=0.003), hypoxanthine 3.02 [1.80; 5.63] vs 7.35 [4.56; 8.25](μmol/l), p=0.008; inosine 1.59 [1.25; 4.48] vs 7.41 [1.49; 17.24](μmol/l), p=0.002. An increase level of a SUA is noted in 31.2% of patients from group 1 (5 patients out of 16) and 68.7% of patients from group 2 (11 patients out of 16). As a result of Spearman's correlation analysis in the group of patients with HTN and AF, a direct correlation was found between the experience of AF and BMI (r=0.681), SBP (r=0.487); level of hypoxanthine and inosine (r=0.808) and the inverse correlation between the level of xanthine and inosine (r=−0.547), as well as the association between the level of XO and SUA (r=0.796), XO and BMI (r=0.812). In the group of patients with HTN was determined association between the level of hypoxanthine and inosine (r=0.604), xanthine and adenosine (r=0.539), inosine and adenosine (r=0.657), a direct association between the level of XO and adenosine (r=0.642), inosine (r=0.502), BMI (r=0.791). Conclusions As a result of the study of patients with isolated HTN in combination with AF at the age of 27 to 65 years and a BMI of less than 30 kg/m2 and more than 18.5 kg/m2, an increase level of SUA and intermediate metabolites of UA synthesis such as inosine and hypoxanthine is observed compared with group with isolated HTN. An increase in level of XO is associated with an increase level of SUA and BMI. In the group of patients with HTN, an increase in level of inosine is associated with an increase level of hypoxanthine, but an increased level of inosine is associated with a decrease in level of xanthine. The XO level in this group is associated with an increase in level of adenosine and inosine, BMI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Grodno State Medical University, Grodno, Belarus Table 1. Comparative characteristics of indicators in groups 1 and 2

Function of Uric Acid Transporters and Their Inhibitors in Hyperuricaemia.

Disorders of uric acid metabolism may be associated with pathological processes in many diseases, including diabetes mellitus, cardiovascular disease, and kidney disease. These diseases can further promote uric acid accumulation in the body, leading to a vicious cycle. Preliminary studies have proven many mechanisms such as oxidative stress, lipid metabolism disorders, and rennin angiotensin axis involving in the progression of hyperuricaemia-related diseases. However, there is still lack of effective clinical treatment for hyperuricaemia. According to previous research results, NPT1, NPT4, OAT1, OAT2, OAT3, OAT4, URAT1, GLUT9, ABCG2, PDZK1, these urate transports are closely related to serum uric acid level. Targeting at urate transporters and urate-lowering drugs can enhance our understanding of hyperuricaemia and hyperuricaemia-related diseases. This review may put forward essential references or cross references to be contributed to further elucidate traditional and novel urate-lowering drugs benefits as well as provides theoretical support for the scientific research on hyperuricemia and related diseases.

Подагрическая (уратная) нефропатия

Clinical variants of kidney damage in gout including asymptomatic disorders of uric acid metabolism are discussed. The risk factor for hyperuricemia and associated kidney damage, clinical variants of gouty nephropathy and approaches to its treatment are presented. Keywords: gout, urate nephropathy, hyperuricemia, uric acid For citation: Fomin VV. Gouty (urate) nephropathy. Consilium Medicum. 2021; 23 (1): 11–14. DOI: 10.26442/20751753.2021.1.200709

Investigation of the Effects and Mechanisms of Dendrobium loddigesii Rolfe Extract on the Treatment of Gout.

Objective Gout is a chronic disease that causes inflammatory arthritis, which is closely related to urate accumulation induced by a disorder of uric acid metabolism and the consequent deposition of monosodium urate crystals. Dendrobium loddigesii Rolfe is an herbal medicine that has been used in some traditional Chinese medicine formulae in the treatment of gout. This study aimed to explore and verify the antigout activity of Dendrobium loddigesii extract (DLE) on alleviating the hyperuricaemia of mice and the acute gouty arthritis of rats. Methods An animal model of hyperuricaemia was established using potassium oxonate (PO). We analysed the expression of uric acid transporter mRNA in the kidney in the hyperuricaemic mice after treatment with DLE. Simultaneously, a monosodium urate crystal-induced acute gouty arthritis rat model was used to evaluate the effects of DLE, according to the level of ankle swelling, as well as the protein levels of inflammatory receptors and cytokines, as assayed by WB and ELISA. Results DLE alleviated hyperuricaemia in mice and inhibited acute gouty arthritis in rats (P < 0.05). Meanwhile, DLE regulated the levels of uric acid transporters mRNA transcripts, including mouse organic anion transporter 1 (mOAT1), organic anion transporter 3 (mOAT3), urate transporter 1 (mURAT1), and glucose transporter 9 (mGLUT9) in the kidney (P < 0.05), suggesting that DLE promoted uric acid metabolism. Furthermore, DLE significantly suppressed the protein levels of TLRs, MyD88, and NF-κB in the ankle joint's synovium (P < 0.05), and the serum levels of IL-1β, IL-6, and TNF-α were also reduced, which demonstrated the anti-inflammatory effects of DLE. Conclusion DLE alleviates hyperuricaemia by regulating the transcription level of uric acid transporters in the kidney. It also inhibits acute gouty arthritis by inhibiting the pathway of TLRs/MyD88/NF-κB in the ankle joint's synovium. The findings of the present study imply that DLE alleviates gout by promoting uric acid metabolism and inhibiting inflammation related to the TLRs/MyD88/NF-κB pathway.

Cytodiagnosis of multiarticular chronic tophaceous gout

Gout is a disorder of uric acid metabolism that causes deposition of Monosodium Urate (MSU) crystals in joint spaces, which, in turn, elicit an acute inflammatory reaction. Gout causes intense pain, swelling and stiffness in a joint. It usually affects the joint in the big toe. We present a case in which diagnosis of gout was made by fine needle aspiration of tophus. FNAC of gouty tophus is an easy alternative to synovial biopsy. It is simpler, easier and less painful. Keywords: Gout, Fine needle aspiration cytology (FNAC), Tophus, Monosodium Urate, Arthropathy.

1869-P: Nonalcoholic Fatty Liver Disease and Insulin Resistance Are Associated via Xanthine Oxidoreductase Activity

Xanthine oxidoreductase (XOR), which is mainly produced by the liver, has been reported to be associated with insulin resistance in addition to disorder of uric acid metabolism, which is common in obese people. Moreover, nonalcoholic fatty liver disease (NAFLD) is known to trigger insulin resistance, but the mechanism has not been sufficiently elucidated. In this study, we used FibroScan equipped with controlled attenuation parameter (CAP) estimation to measure intrahepatic fat accumulation and to evaluate the association of insulin resistance with intrahepatic fat accumulation and XOR activity by adjusting for the effects of visceral fat. Of the 200 individuals who had undergone health checkups at our medical center, 142 individuals (59 men) were included in the study after excluding 58 individuals because of incomplete data, habitual alcohol consumption, or ongoing treatment with hypoglycemic and antihyperuricemic agents. NAFLD was defined as a CAP value ≥236 dB/m. Plasma XOR activity was measured by liquid chromatography-triple quadrupole mass spectrometry using [13C2, 15N2] xanthine as a stable isotope substrate developed by Sanwa Kagaku Kenkyusho Co., Ltd. The association of insulin resistance (HOMA-IR ≥2.5) with NAFLD was analyzed by multivariate logistic analysis while adjusting the effects of other factors. NAFLD, as well as visceral fat area, were found to be an independent explanatory factor for insulin resistance. However, when logarithmic values of XOR activity levels (ln-XOR) were added to the analysis model, ln-XOR, but not NAFLD, was a significant explanatory factor for insulin resistance (odds ratio [95% confidence interval]: 4.36 [2.21-8.60]). This finding suggested that XOR of the liver was involved in the association between NAFLD and insulin resistance. In conclusion, NAFLD and insulin resistance are associated via XOR Activity. Disclosure S. Fukumoto: Research Support; Self; Astellas Pharma Inc., Chugai Pharmaceutical Co., Ltd., Kowa Pharmaceutical Europe Co. Ltd., Mitsubishi Tanabe Pharma Corporation, Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Novo Nordisk Inc., Sanofi K.K. M. Kurajoh: None. T. Nakamura: None. T. Murase: None. Y. Kakutani: None. Y. Yamazaki: None. A. Ochi: None. K. Motoyama: None. T. Morioka: Research Support; Self; Eli Lilly and Company, Merck &amp; Co., Inc., Mitsubishi Tanabe Pharma Corporation, Novartis Pharmaceuticals Corporation, Sanofi K.K., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Merck &amp; Co., Inc., Novo Nordisk Inc., Roche Diagnostics K.K., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Other Relationship; Self; Ono Pharmaceutical Co., Ltd. T. Shoji: Research Support; Self; Bayer Yakuhin, Ltd., Chugai Pharmaceutical Co., Ltd., Ono Pharmaceutical Co., Ltd. Speaker's Bureau; Self; Kissei Pharmaceutical Co., Ltd., Kowa, Kyowa Hakko Kirin Co., Ltd. M. Emoto: Research Support; Self; Ono Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd. Speaker's Bureau; Self; Astellas Pharma Inc., Boehringer Ingelheim Pharmaceuticals, Inc., Daiichi Sankyo Company, Limited, Eli Lilly and Company, Kowa Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Novartis Pharmaceuticals Corporation, Novo Nordisk Inc., Ono Pharmaceutical Co., Ltd., Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical CO., Ltd., Takeda Pharmaceutical Company Limited. M. Inaba: None. Funding Japan Society for the Promotion of Science

50 Years Ago in The Journal of Pediatrics: Uric Acid Levels in Full-Term and Low-Birth-Weight Infants

Marks JF, Kay J, Baum J, Curry L. J Pediatr 1968;73:609-11. In the 1960s, uric acid became a metabolite of interest in the newborn. The main reason was the description by Lesch and Nyhan in 1964 of a new X-linked syndrome characterized by mental retardation, spasticity, and self-mutilation.1Lesch M. Nyhan W.L. A familial disorder of uric acid metabolism and central nervous system function.Am J Med. 1964; 36: 561-570Abstract Full Text PDF PubMed Scopus (900) Google Scholar In 1967, it was reported that deficiency of the enzyme hypoxanthine guanine phosphoribosyl transferase, which is needed for purine salvage, was present in these patients.2Seegmiller J.E. Rosenbloom F.M. Kelly W.N. Enzyme defect associated with a human sex-linked neurological disorder and excessive purine synthesis.Science. 1967; 155: 1682-1684Crossref PubMed Scopus (729) Google Scholar This is the background for the study by Marks et al in The Journal 50 years ago reporting serum uric acid levels in full term and low-birth weight infants the first days of life. In full-term infants cord blood levels were higher than maternal levels peaking at day 1 declining to maternal levels at day 2. In low birth weight infants, uric acid reached higher levels than in full-term infants with a peak 1 day later. Still, the values of 5-6 mg/100 mL was far below levels of a patient with the Lesch-Nyhan syndrome of 8.0 mg/100 mL in cord blood and 18.9 mg/100 mL at the age of 24 hours.3Marks J.F. Baum J. Keele D.K. Kay J.L. MacFarlen A. Lesch-Nyhan syndrome treated from early neonatal period.Pediatrics. 1968; 42: 357-359PubMed Google Scholar In the early 1970s, a new interest in uric acid among newborns was aroused due to its potentiality as an asphyxia marker. Thus, Raivio found higher serum uric acid concentrations the first 3 days of life in premature infants with respiratory distress syndrome compared with normal term infants.4Raivio K. Neonatal hyperuricemia.J Pediatr. 1976; 88: 625-630Abstract Full Text PDF PubMed Scopus (32) Google Scholar It was, however, understood that hypoxanthine—the precursor of uric acid—is a more sensitive marker of hypoxia than uric acid. Today uric acid is recognized as an important antioxidant in the newborn period explaining why a peak immediately after birth may be beneficial. However, in spite of a high uric acid level, an increased oxidative stress probably is present in patients with Lesch-Nyhan.5Saugstad O.D. Marklund S.L. High activities of erythrocyte glutathione peroxidase in patients with the Lesch-Nyhan syndrome.Acta Med Scand. 1988; 224: 281-285Crossref PubMed Scopus (11) Google Scholar

Hyperuricemia and diuretic therapy – how not to harm the patient?

Hyperuricemia is a disorder of uric acid metabolism, which can become a prerequisite for the development of gout. It can be primary (idiopathic) or secondary (acquired), both of these types of hyperuricemia may be the result of an increase in the production or a reduction in the excretion of uric acid from the body. Such a pathological condition can serve as an independent predictor of the development of cardiovascular diseases, and also contribute to the fatal outcome of arterial hypertension or coronary heart disease. Therefore, in the treatment of cardiovascular diseases, when there is a need for diuretics, it is recommended to appoint thorasemide, since it, in comparison with other representatives of the group (indapamide, furosemide) does not affect the level of uric acid, but also does not lead to the development of hyperuricemia.

Gouty tophi without hyperuricemia, an interesting case diagnosed by fine-needle aspiration cytology

Gout is a disorder of uric acid metabolism characterized by deposition of monosodium urate crystals in joint spaces or soft tissues. Gouty tophi can be the presenting feature of gout and can occur despite normal serum uric acid levels. Periarticular nodules can be a diagnostic dilemma for both clinicians and radiologists. A 39-year-old man presented with a nontender, firm swelling in right medial malleolus. His serum uric acid level was normal. Computed tomography scan report gave a differential diagnosis of synovial sarcoma and pigmented villonodular synovitis. Fine-needle aspiration cytology from the swelling revealed abundant granular amorphous deposits with needle-shaped crystals in a background of chronic inflammatory infiltrate. Biopsy from the swelling demonstrated the presence of needle-shaped crystals in a radial arrangement along with foreign-body giant cells and histiocytes. On the basis of cytological and histopathological findings, a diagnosis of gouty tophi was rendered.

Unusual Gouty Tophi Simulating Malignancy.

©2016 Turkish League Against Rheumatism. All rights reserved. Gout is a disorder of uric acid metabolism, characterized by deposition of monosodium urate crystals in joints and periarticular soft tissues as well as renal calculi and chronic nephropathy. The accumulation of crystals in the joints and periarticular soft tissues may cause recurrent episodes of inflammatory arthritis. Over the years, chronic form may occur with the presence of tophi and chronic arthropathy frequently in peripheral and rarely in axial joints. Surgical intervention is usually reserved for cases of recurrent attacks with deformities, severe pain and joint destruction.1 In this article, we present a case of tophaceous gout with destructive bony changes simulating malignancy in X-ray which, to the best of our knowledge, has not been reported previously. In addition, we emphasize the importance of early debridement of tophi to avoid amputation.

Gout and Hyperuricemia: an Historical Perspective

Gout is a common disorder of uric acid metabolism. A disease of antiquity its’ often dramatic presentation and unique manifestations have been familiar for eons to clinicians and to its sufferers. Effective modern therapies may have downgraded its status, yet it’s long, rich history remains a source of fascination, indeed entertainment to those with an interest in the pathophysiology of disease, therapeutic discovery, indeed with the annals of medicine. This paper reviews the history of one of the oldest afflictions of mankind. ᅟ

Cytodiagnosis of Gouty Arthritis

Gout is a disorder of uric acid metabolism that causes deposition of Monosodium Urate (MSU) crystals in joint spaces, which, in turn, elicit an acute inflammatory reaction. We present a case in which diagnosis of gout was made by fine needle aspiration of tophus. FNAC of gouty tophus is an easy alternative to synovial biopsy. It is simpler, easier and less painful.

Defining neurogenetic phenotypes (or how to compare needles in haystacks)

Accurate diagnosis is the foundation of clinical neurology, providing both the physician and the patient with a guide to the future, hopefully leading to a treatment, and sometimes pointing towards a cure. Unlike many other clinical disciplines, the day-to-day practice of neurology involves a pantheon of symptoms and long lists of differential diagnoses. The challenge is to spot the rarities, especially if this is going to influence clinical management. This should be much easier in 2010, given recent advances in the routine diagnostic armamentarium; but paradoxically it seems more difficult, as we continue to dissect sub-categories of common disorders and overlapping clinical spectrums expand. So what are the distinguishing features of a particular disorder, and how can we reliably define them? This is particularly difficult if they are exceptionally rare ‘once in a lifetime’ diagnoses. Two papers in this edition of Brain tackle this issue for two important genetic neurometabolic disorders (Jinnah et al. , 2010; Leen et al. , 2010), illustrating an emerging approach to this thorny topic. In 1964, the medical student Michael Lesch and the paediatrician Bill Nyhan published the classic description of two brothers, aged 4 and 8, with a new familial disorder of uric acid metabolism and central nervous system dysfunction (Lesch and Nyhan, 1964). The primary biochemical defect was defined within a few years, affecting the enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT) (Seegmiller et al. , 1967), ultimately leading to the identification of recessive mutations in the X-chromosomal disease gene HPRT1 . After a normal pregnancy and birth, Lesch–Nyhan disease typically presents with developmental delay in the first year of life, most noticeably affecting the motor system, and leading to delayed sitting, crawling and walking. Involuntary movements develop before school age, with dystonia and choreoathetosis, leading on to spasticity that prevents affected boys from walking …

Lesch–Nyhan syndrome: Reconstruction of a calcaneal defect with a sural flap

Lesch-Nyhan syndrome is a familial disorder of uric acid metabolism and dysfunction of the central nervous system. We present a patient with the syndrome, who had a defect of the left calcaneal tissue with osteomyelitis caused by repeated self-mutilation. The defect was reconstructed with a sural flap.

Genomewide Scan for Gout in Taiwanese Aborigines Reveals Linkage to Chromosome 4q25

Gout is a disorder of uric-acid metabolism. The Pacific Austronesian population, including Taiwanese aborigines, has a remarkably high prevalence of hyperuricemia and gout, which suggests a founder effect across the Pacific region. We report here a genomewide linkage study of 21 multiplex pedigrees with gout from an aboriginal tribe in Taiwan. From observations of familial clustering, early onset of gout, and clinically severe manifestations, we hypothesized that a major gene plays a role in this trait. Using 382 random polymorphic markers spread across 22 autosomes, we demonstrated a highly significant linkage for gout at marker D4S2623 on chromosome 4q25 (P=.0002 by nonparametric linkage [the NPL(all) statistic]; empirical P=.0006; LOD=4.3, P=4.4x10-6 by logistic regression). When alcohol consumption was included as a covariate in the model, the LOD score increased to 5.66 (P=1.3x10-6). Quantitative traits, including serum uric acid and creatinine, also showed a moderate linkage to this region. To our knowledge, this is the first genome-scan report to identify a genetic locus harboring a gout-susceptibility gene.

Hirsutism–skeletal dysplasia–mental retardation syndrome with abnormal face and a uric acid metabolism disorder

We report on a German boy, born to nonconsanguineous parents, with an apparently new combination of multiple congenital anomalies including extraordinary hirsutism, marked brachycephaly, abnormal position of thumbs, pedes excavati with claw-toes, an abnormal face, and mental retardation. Additionally the boy manifests a disorder of uric acid metabolism. This sporadic case may represent a new syndrome due to a fresh autosomal or X-linked mutation, or chance-isolated case due to segregation of an autosomal recessive gene.