Metabolic disorder of amino acids, fatty acids and purines reflects the decreases in oocyte quality and potential in sows.

Oocyte quality is closely related to female fertility. Nevertheless, core nutritional metabolites influencing oocyte quality are unclear. Herein, comprehensive metabolomics analysis of follicular fluid, serum, and urine from low reproductive performance (LRP) and normal reproductive performance (NRP) sows was conducted. Twenty-seven, fourteen and sixteen metabolites (involved in metabolism of amino acids, fatty acids, purine and pyrimidine) were altered in follicular fluid, serum and urine, respectively, in LRP compared with NRP sows, and could decrease oocyte quality and developmental potential, ultimately leading to low fertility. Deoxyinosine, guanidine acetate, thymidine, 5,6-epoxy-eicosatrienoic acid, carnosine, docosahexaenoic acid and carbamoyl phosphate in follicular fluid, cysteine, carnitine, serotonin, hypoxanthine, valine and arginine in serum, as well as carnitine, phenyl glycine, N-acetyl glutamine, propionyl carnitine and choline in urine could be selected as diagnostic markers to indicate oocyte quality. Consistent with metabolomics data, we confirmed changes in concentrations of fatty acids and amino acids in follicular fluid. Targeting purine metabolism, elevating levels of deoxyinosine in in-vitro maturation medium of porcine oocyte significantly promoted the blastocyst rate. Collectively, this study provided new information of potential targets for predicting oocyte quality and developmental potential, and may help with strategies for early diagnosis or therapeutic/dietary intervention in improving reproductive outcomes.

Association of urinary concentrations of four chlorophenol pesticides with cardiometabolic risk factors and obesity in children and adolescents.

This study was undertaken to determine the association of four chlorophenol pesticides with cardiometabolic risk factors and obesity in children and adolescents. This cross-sectional study was conducted in 2016 on 242 children and adolescents, aged 6 to 18 years. The concentrations of 2,4-dichlorophenol (2,4-DCP), 2,5-dichlorophenol (2,5-DCP), 2,4,5-trichlorophenol (2,4,5-TCP), and 2,4,6-trichlorophenol (2,4,6-TCP) in the urine were examined and their association with indices of obesity and cardiometabolic risk factors was determined. Multivariate linear regression and multinomial logistic regression analyses were applied. Overall, 242 participants with mean (SD) ages of 11.3 (2.5) years completed the survey. After adjustment for confounders, a significant positive association was found between body mass index (BMI) z-score and waist circumference (WC) with 2,5-DCP (0.07 (95% CI 0.04, 0.1)) and 0.79 (95% CI 0.54, 1.03), respectively. A significant association of 2,4,5-TCP was only found with WC (0.23 (95% CI 0.0, 0.46), but the relationship with 2,4-DCP was not significant. 2,5-DCP had a significant relationship only with obesity (1.09 (95% CI 1.1, 1.19)), while 2,4-DCP and 2,4,5-TCP showed no significant correlation with overweight or obesity. 2,4-DCP showed a significant positive relationship with high density lipoprotein-cholesterol (HDL-C). Moreover, 2,5-DCP showed a significant negative relationship only with systolic blood pressure and 2,4,5-TCP had a statistically significant inverse association with total cholesterol and HDL-C (-0.71 (95% CI -0.98, -0.45)). This study suggests potential associations of chlorophenol pesticides with overweight, obesity, lipid profile, and blood pressure in children and adolescents. Longitudinal studies are necessary to assess the clinical impact of these findings.

Intraventricular Glioblastoma Multiforme in A Child with L2-Hydroxyglutaric Aciduria.

L2-hydroxyglutaric aciduria (L2-HGA) is a rare neurometabolic disease characterized by accumulation of L2-hydroxyglutarate (L2-HG), a potential oncometabolite resulting in significant lifetime risk for cerebral tumors. Herein, we present a case of intraventricular glioblastoma multiforme (GBM) in a 16-year-old child with L2-HGA who presented with rapid functional decline and persistent vomiting. The tumor was completely resected, and the patient remained well at 2-year follow-up. Clinicians should be aware of the usual insidious nature of the disease. Rapid deterioration is unusual and should raise the suspicion of tumor development. This case also illustrates the importance of surveillance neuroimaging in patients with L2-HGA. To the best of our knowledge, only 1 case of GBM has been reported and it was sited in the temporal lobe, unlike the unusual intraventricular location in our case.

Metabolic Work-up of Patients with Urolithiasis: Indications and Diagnostic Algorithm.

CONTEXT: The incidence of urinary tract stone disease is increasing and the risk of recurrent stone formation is high. Appropriate therapeutic procedures with the aim of counteracting the progress of stone formation are highly desirable. Metabolic work-up is considered essential as a base for optimal design and follow-up of effective recurrence prevention. OBJECTIVE: To scrutinize the current literature with regard to principles of metabolic work-up for this heterogeneous group of patients. EVIDENCE ACQUISITION: Relevant articles in PubMed, guideline documents, consensus reports, and the Cochrane Library published during the past 20 yr were consulted. EVIDENCE SYNTHESIS: Grades of recommendation were used according to the principles applied in the European Association of Urology and American Urological Association guidelines. Medical efforts to prevent recurrent stone formation should be part of the care of patients with urinary tract stone disease (grade of recommendation A). A careful medical history and imaging together with analysis of stone composition, blood, and urine provide the basis for appropriate measures, but the treatment has to be individualized (grade of recommendation D). Whenever possible, stone analysis should be carried out at least once for every patient or each time when a long time has elapsed between two stone episodes because the risk factors explaining stone formation may have changed (clinical principle). The medical history, including information on dietary and drinking habits as well as lifestyle, is necessary for appropriate advice (grade of recommendation C). The medical history, together with imaging and stone composition, is used to estimate the severity of the disease (clinical principle). Identification of specific medical conditions should be supported by blood and/or urine analysis (grade of recommendation B). Pharmacological agents associated with an increased risk of stone formation should be identified (grade of recommendation C). Patients who have formed noncalcium stones should always be given recurrence preventive treatment. Analysis of urine composition for these patients is optional, but might be of value in the follow-up to support decisions on appropriate dosage regimens (grade of recommendation C). For patients with idiopathic calcium stone disease information from 24-h urine samples should be used, although the number of samples to be taken is debated (grade of recommendation C). Information from 24-h urine analysis should be used for selective dietary and drinking advice as well as for selection of the most appropriate pharmacological agent (grade of recommendation B). The treatment effects on the risk of stone formation can be followed by estimates of supersaturation based on urine composition (grade of recommendation C). CONCLUSIONS: It is clear that the metabolic work-up of patients with urinary tract stone disease should be individualized according to stone type and severity of the disease, and that the different therapeutic approaches are closely associated with the availability of therapeutic tools and motivation by the patient. PATIENT SUMMARY: Effective prevention of recurrent stone formation is determined by several factors such as the current and previous stone episodes and surgical procedures, stone composition, medical history, dietary and drinking habits, lifestyle, and ongoing pharmacological therapy. Analysis of blood and urine is an important part of the metabolic evaluation, but how extensive the risk evaluation should be is determined by the type of stone and the severity of the disease.

Fabrication of nitrogen-doped carbon dots for screening the purine metabolic disorder in human fluids.

Fabrication of nitrogen-doped carbon dots (N-CDs) electrode for the screening of purine metabolic disorder was described in this paper. Peroxynitrite is a short-lived oxidant species that is a potent inducer of cell death. Uric acid (UA) can scavenge the peroxynitrite to avoid the formation of nitrotyrosine, which is formed from the reaction between peroxynitrite and tyrosine (Try). Scavenging the peroxynitrite avoids the inactivation of cellular enzymes and modification of the cytoskeleton. Reduced level of UA decreases the ability of the body from preventing the peroxynitrite toxicity. On the other hand, the abnormal level of UA leads to gout and hyperuricemia. Allopurinol (AP) is administered in UA lowering therapy. Thus, the simultaneous determination of UA, Try and AP using N-CDs modified glassy carbon (GC) electrode was demonstrated for the first time. Initially, N-CDs were prepared from L-asparagine by pyrolysis and characterized by different spectroscopic and microscopic techniques. The HR-TEM image shows that the average size of the prepared N-CDs was 1.8±0.03nm. Further, the N-CDs were directly attached on GC electrode by simple immersion, follows Micheal's nucleophilic addition. XPS of N-CDs shows a peak at 285.3eV corresponds to the formation of C-N bond. The GC/N-CDs electrode shows higher electrocatalytic activity towards UA, Tyr and AP by not only shifting their oxidation potentials toward less positive potential but also enhanced their oxidation currents in contrast to bare GC electrode. The GC/N-CDs electrode shows the limit of detection of 13×10-10M (S/N=3) and the sensitivity of 924µAmM-1cm-2 towards the determination of UA. Finally, the N-CDs modified electrode was utilized for the determination of UA, Tyr and AP in human blood serum and urine samples.

Cadmium-Induced Oxidative Stress Impairs Glycemic Control in Adolescents.

Experimental evidence suggests that cadmium (Cd) boosts oxidative stress that may result in toxicity on the endocrine system also in humans. The aim of this study was to investigate the glycemic control and oxidative stress markers in male adolescents with increased urinary levels of cadmium. We investigated 111 males, aged 12-14 years, living in a polluted area of Sicily and a control age-matched population (n = 60) living 28-45 km far from the polluted site. Malondialdehyde (MDA), total antioxidant activity (TAC), metallothionein-1A (MT-1A) gene expression, insulin resistance by the homeostatic model assessment (HOMA-IR), and urinary cadmium were investigated. Cd levels were significantly higher in adolescents living in the polluted area than in control age-matched subjects. Adolescents with elevated Cd levels had a significant increase in MDA, MT-1A, and HOMA-IR and reduced TAC compared to the control group. A robust correlation was found between urinary cadmium and MT-1A, HOMA-IR, and MDA whereas an inverse correlation was identified between urinary cadmium and TAC. This study indicates that cadmium burden alters glycemic control in adolescents and suggests that oxidative stress plays a key role in cadmium-induced insulin resistance, increasing the risk of developing metabolic disorders.

Are patients with lichen planus really prone to urolithiasis? Lichen planus and urolithiasis

ABSTRACT Purpose to investigate whether patients with lichen planus (LP) are really prone to urolithiasis or not. Patients and Methods We performed a prospective analysis of 40 patients diagnosed with lichen planus (LP) (group I), and 40 volunteers did not have LP before (group II). Participants were all checked for urolithiasis by radiological investigations. Blood samples were analyzed for biochemistry parameters including calcium and uric acid. 24-h urine samples were analyzed to investigate oxalate, citrate calcium, uric acid, magnesium, sodium and creatinine. Results Men/women ratio and mean age were similar between group I and II (p>0.05). A presence or history of urolithiasis was detected in 8 (20%) and 2 (%5) patients in group I and II, respectively (p<0.05). Hypocitraturia was the most common anomaly with 35% (n:14) in group I. The rate of hypocitraturia in group II was 12.5% (n:5) and the difference was statistically significantly different (p=0.036). In group I, hyperuricosuria and hyperoxaluria followed with rates of 27.5% (n:11) and 25% (n:10), respectively. The rate of hyperuricosuria and hyperoxaluria were both 5% (n:2) in group II and the differences were significant (p<0.05). Hyperuricemia was another important finding in the patients with LP. It was detected in 13 (32.5%) patients in group I and in 1 (2.5%) participant in group II (p=0.001). Conclusion According to our results, metabolic disorders of urolithiasis were highly detected in the patients with LP. However, similar to the etiology of LP, the exact reasons for these metabolic abnormalities in LP remain a mystery.

Qualitative urinary organic acid analysis: 10 years of quality assurance.

Over the last 10 years, a total of 90 urine samples from patients with metabolic disorders and controls were circulated to different laboratories in Europe and overseas, starting with 67 laboratories in 2005 and reaching 101 in 2014. The participants were asked to analyse the samples in their usual way and to prepare a report as if to a non-specialist pediatrician. The performance for the detection of fumarase deficiency, glutaric aciduria type I, isovaleric aciduria, methylmalonic aciduria, mevalonic aciduria, phenylketonuria and propionic aciduria was excellent (98-100 %). Over the last few years, detection has clearly improved for tyrosinaemia type I (39 % in 2008 to over 80 % in 2011/2014), maple syrup urine disease (85 % in 2005 to 98 % in 2012), hawkinsinuria (62 % in 2010 to 88 % in 2014), aminoacylase I deficiency (43 % in 2009 to 73 % in 2012) and 3-methylcrotonyl-CoA carboxylase deficiency (60 % in 2005 to 93 % by 2011). Normal urines were mostly considered as normal (83-100 %), but laboratories often made additional diagnostic suggestions. When the findings were unambiguous, the reports were mostly clear. However, when they were less obvious, the content and quality of reports varied greatly. Repetition of organic acid measurements on a fresh sample was rarely suggested, while more complex or invasive diagnostic strategies, including further metabolic screening or biopsy were recommended. Surprisingly very few participants suggested referral from the general paediatrician to a specialist metabolic centre to confirm a diagnosis and, if applicable, to initiate treatment despite evidence suggesting that this improves the outcome for patients with inherited metabolic disorders. The reliability of qualitative organic acid analysis has improved over the last few years. However, several aspects of reporting to non-specialists may need discussion and clinicians need to be aware of the uncertainty inherent in all forms of laboratory diagnostic analysis.

Crystalluria.

Crystalluria is a marker of urine supersaturation with substances deriving from metabolic disorders, inherited diseases or drugs. The investigation of crystalluria must be done according to a protocol which includes the delivery to the laboratory of a proper urine sample, the use of a microscope equipped with polarized light, the accurate knowledge of urine pH, and a comprehensive examination of the crystals, which is based on their identification, quantification and size measurement. For unusual crystals, infrared spectroscopy may also be needed. The main urinary crystalline categories include: calcium oxalates, calcium phosphates, uric acids and urates, struvite, aminoacids (cystine), purines (2,8-dihydroxyadenine and xanthine) and drugs (e.g. sulfamethoxazole, amoxycillin, ceftriaxone, atazanavir). The investigation of crystalluria is a cheap and valuable tool for the detection and the monitoring of inherited and acquired diseases associated with urinary stone formation or renal function impairment - either acute or chronic - due to intrarenal crystal precipitation.

Biochemical diagnosis in 3040 kidney stone formers in Argentina.

Nephrolithiasis is a frequent condition in urology that has an important recurrence and high impact in health economy. Knowing the biochemical abnormalities implicated in its pathogenesis is mandatory to establish therapeutic aims. Our objectives are to present the results in 3040 kidney stone formers in Argentina. All patients were selected after completing an ambulatory metabolic protocol with diagnostic purposes. There were 1717 men, (56.48%), with a mean age of 45±12 years, and 1323 women, (43.52%), mean age 44±12 years. 2781 patients had biochemical abnormalities, (91.49%), and were arbitrarily divided in two groups: those who had only one (single) biochemical abnormality (n=2156) and those who had associated abnormalities (n=625). No biochemical abnormalities were found in 259 patients (8.51%). The abnormalities present, single and associated, in order of frequency, were idiopathic hypercalciuria, (56.88%), hyperuricosuria (21.08%), unduly acidic urine (10.95%), hypocitraturia (10.55%), hypomagnesuria (7.9%), primary hyperparathyroidism (3.01%), hyperoxaluria (2.6%), and cystinuria (0.32%). We performed in 484 patient's stone composition and found calcium oxalate stones related to idiopathic hypercalciuria predominantly while uric acid stones to unduly acidic urine. In conclusion, the biochemical abnormalities described are similar to those found in a previous series of our own and to those reported in the literature. Its diagnosis is important to therapeutic purposes to avoid eventual recurrence.

Screening of Inherited Metabolic Disorders in Infants with Infantile Spasms.

The objective of this study is to explore the incidence of inherited metabolic disorders (IMD) in infants with infantile spasms (IS), with an attempt to improve the early diagnosis and etiological and symptomatic treatment. Urine and blood samples were collected from 60 IS patients and analyzed for the quantification of amino acids, organic acids, and fatty acids by gas chromatography-mass spectrometry and tandem mass spectrum. Routine urine tests, hepatic function tests, blood biochemistry, brain imaging, as well as examinations of the brain stem auditory/visual evoked potentials were also examined. In addition to antiepileptic therapy, etiological and symptomatic treatments were also conducted in infants with confirmed IMD and the follow-up lasted for 6 months in these pediatric patients. Metabolic disorders were found in 28 (46.67 %) of 60 IS infants, among them 13 (21.67 %) were confirmed to be with IMD. Twelve of these 13 IS patients with definite IMD diagnoses (92.31 %) experienced varying degrees of delayed development of intelligence and motor function, 8 patients (61.54 %) had abnormal cranial CT or MRI findings, 11 patients (84.61 %) had abnormal brain stem evoked potentials, 4 patients (30.77 %) had abnormal hepatic functions, 3 patients (23.07 %) had abnormal blood biochemistry, 2 patients (15.38 %) had positive (+ to ++) results for routine urine ketones, and 2 patients (15.38 %) had skin lesions. After treatment in children who were diagnosed IMD, the well controlled epileptic seizures and the satisfactory developments in mental and motor were found in 4 cases of methylmalonic acidemia, 2 cases of classical phenylketonuria, and one case of biotin deficiency disease, glutaric acidemia type I, and 4-hydroxybutyric aciduria in each. IMD is a key biological cause in IS. Early screening for IMD is warranted in IS infants to facilitate the improvement for the prognosis and an early etiological treatment.

Ezetimibe ameliorates metabolic disorders and microalbuminuria in patients with hypercholesterolemia.

AIM: Ezetimibe, an inhibitor of Niemann-Pick C1-like 1 protein, has been shown to reduce the intestinal absorption of cholesterol. We investigated whether it also has beneficial effects on metabolic disorder and/or renal insufficiency in patients with hypercholesterolemia. METHODS: Ezetimibe was administered to 38 Japanese patients with hypercholesterolemia to obtain appropriate low-density lipoprotein cholesterol (LDL-chol) levels. Age- and sex-matched patients with hypercholesterolemia (n=38) were the controls. We evaluated the effects of ezetimibe before and 4 to 8 weeks after ezetimibe treatment. RESULTS: Ezetimibe significantly decreased LDL-chol levels and metabolic syndrome-related factors, including body weight, waist circumference, blood pressure; homeostasis model assessment insulin resistance (HOMA-IR), and urinary albumin excretion, were significantly reduced. In addition, it decreased the level of high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor (TNF)-alpha, the urinary excretion of 8-hydroxy-2'-deoxyguanosine, a parameter of oxidative stress, and increased the urinary excretion of nitrate and nitrite (NOx). In the controls we observed no such changes. Excepting the decrease in the serum TNF-alpha level, the effects of ezetimibe were not correlated with decreased LDL-chol levels. CONCLUSION: Ezetimibe ameliorated the status of metabolic syndrome and microalbuminuria, reduced inflammation and oxidative stress, and increased nitric oxide bioavailability in a LDL-chol reduction-dependent and -independent manner.

Clinical manifestations and etiology of renal stones in children less than 14 years age.

Urolithiasis is one of the commonest problems in pediatric nephrology. Prevalence of urolithiasis in pediatric patients is increasing. The purpose was to properly diagnose and treat with the special attention to the risk factors. This study is case-series and was performed on 100 pediatric patients for evaluation of clinical manifestation and etiology of renal stone in Qom. Hundred Children, fewer than 14 years old with mean age of 3.32 years, were included (54% male). Etiology of urolithiasis in 5% was unclear. Metabolic disorders found in patients were mainly: Hypocitraturia in 54, hyperoxaluria in 14, hyperuricosuria in 25, cystinuria in 6, hypercalciuria in 28 and phosphaturia in 8 patients. The main clinical presentation was fever, pain, irritability, dysuria and hematuria. Family history of urolithiasis was found in 23% of patients and 54% presented with urinary tract infection (UTI). We conclude that majority of patients were symptomatic and hypocitraturia was the commenest risk factor among others.

Urolithiasis in the first year of life.

Data on urolithiasis (UL) in infancy are limited. The objective of this study was to increase awareness of infant UL and to investigate the influence of possible risk factors in this very specific age group. Nonfasting, second-voiding urine samples were obtained to test for urinary excretions of calcium, oxalate, citrate, magnesium, uric acid, and creatinine. Blood analysis included calcium, phosphate, magnesium, uric acid, creatinine, sodium, potassium, chloride, and alkaline phosphatase. Patients received follow-up testing every 1-2 months; serial ultrasonography was used to track UL status. Fifty infants with a median age of 5 months were enrolled in the study. Hypercalciuria was detected in 9/47, hyperoxaluria in 5/39, hypocitraturia in 4/31, and cystinuria in 2/50 infants. We identified at least one metabolic abnormality in 46% of our patients; no metabolic abnormality was identified in 27 infants. Within a mean follow-up period of 14 months, 17 infants became stone free, stones increased in number in ten patients and decreased in number in 16, and recurrence was detected in seven. This study showed that UL could be detected in very early life, even in the newborn period, and could be the source of late childhood/adulthood UL. Infants with nonspecific symptoms such as restlessness may have UL and should undergo ultrasonographic examination. Metabolic evaluation of UL in this specific age group carries some diagnostic challenges, e.g. unsatisfactory data regarding normal ranges of urinary mineral excretion, and collection of 24-h urine samples.

Quality of analytical performance in inherited metabolic disorders: the role of ERNDIM.

External quality assurance (EQA) schemes are essential for improvement of accuracy, reliability and comparability of results of biochemical genetic tests. ERNDIM (European Research Network for evaluation and improvement of screening, Diagnosis and treatment of Inherited disorders of Metabolism), established in 1994, operates nine EQA schemes for biochemical genetic testing according to international norms and recommendations. These comprise qualitative schemes for amino acids, organic acids, purines and pyrimidines, special assays in serum and urine and white cell cystine, qualitative organic acid and acylcarnitine schemes, as well as diagnostic proficiency testing. The total number of participants has increased from 123 in 1994 to 268 in 2007. Additional activities include participation in the Eurogentest project, a laboratory directory, training, education and development of guidelines. Results from the quantitative amino acid scheme with 170 participants reveal good variation within and between laboratories of below 10% for 10 amino acids; good within-laboratory variation but intermediate inter-laboratory variation of 10-22% for 11 amino acids; and higher variation within and between laboratories for 8 amino acids. Results on samples from 51 inherited metabolic disorders from two of five centres organizing diagnostic proficiency testing indicate overall diagnostic efficiency above 80% and improved performance of individual laboratories. Comparison of results for 10 and 12 compounds in the serum and urine special assay schemes respectively for 2000 and 2007 reveal clear improvement of precision within laboratories and in inter-laboratory variation. There is considerable evidence that performance in biochemical genetic testing has improved since the introduction of ERNDIM schemes.

Improvement of sample throughput using fast gas chromatography mass-spectrometry for biochemical diagnosis of organic acid disorders.

BACKGROUND: Gas chromatograph mass-spectrometric (GC/MS) method of analysis for urinary organic acids is used for the diagnosis of a variety of metabolic disorders. The method is time-consuming and does not allow for improvements in sample throughput. Although the sample preparation and the data processing have been improved, the long GC/MS analysis time still remains to be problematic. METHODS: The fast-GC/MS method, which utilizes a short microbore capillary GC column and fast temperature programming, was applied to the analysis for urinary organic acids. Urine samples obtained from 15 patients with 9 different disorders and 16 healthy controls were analyzed using conventional GC/MS and fast-GC/MS. RESULTS: Analysis cycle time was shortened from 1 h to 15 min. The automated data system uses retention indices determined by conventional-GC/MS for the identification of 134 organic acids. These retention indices can also be used in data obtained by fast-GC/MS. New fast-GC/MS method with the automated data system gave the same diagnostic results as conventional-GC/MS except for 1 healthy control. CONCLUSIONS: The combined system of fast-GC/MS and the automated data system will be powerful tools in clinical laboratories due to increased sample throughput and reduced analysis costs.

Investigation of a wide spectrum of inherited metabolic disorders by 13C NMR spectroscopy.

High-resolution (1)H NMR spectroscopy of body fluids has proved to be very useful in diagnostics of inherited metabolic diseases, whereas (13)C NMR remains almost unexploited. In this paper the application of (13)C NMR spectroscopy of fivefold concentrated urine samples for diagnosis of selected metabolic diseases is reported. Various marker metabolites were identified in test urine samples from 33 patients suffering from 10 different diseases, providing information which could be crucial for their diagnoses. Spectra were accumulated for 2 h or overnight when using spectrometers operating at 9.4 or 4.7 T magnetic fields, respectively. Interpretation of the measurement results was based on a comparison of the peak positions in the measured spectrum with reference data. The paper contains a table with (13)C NMR chemical shifts of 73 standard compounds. The method can be applied individually or as an auxiliary technique to (1)H NMR or any other analytical method.

Medical evaluation and treatment of urolithiasis.

Nephrolithiasis is responsible for 1 in 1000 to 1 in 7600 pediatric hospital admissions annually throughout the United States. Seventy-five percent of children with nephrolithiasis have an identifiable predisposition to stone formation. This article reviews the different causes and disease states associated with nephrolithiasis in the pediatric population. The initial evaluation and the metabolic evaluation of children with nephrolithiasis are reviewed. Treatment modalities for the different stone types are also described.

The W258X mutation in SLC22A12 is the predominant cause of Japanese renal hypouricemia.

Recently, a urate transporter, hURAT1 (human uric acid transporter 1) encoded by SLC22A12, was isolated from the human kidney. hURAT1 is presumed to play the central role in reabsorption of urate from glomerular filtrate. In the present study, we analyzed SLC22A12 in seven unrelated Japanese patients with renal hypouricemia whose serum level of urate was less than 1.0 mg/dl, and their family members. We performed direct DNA sequencing of the exon and exon-intron boundaries of SLC22A12 using genomic DNA. Six of the seven patients (86%) possess mutations in SLC22A12. In five patients, a homozygous G to A transition at nucleotide 774 within exon 4 of SLC22A12, which forms a stop codon (TGA) at codon 258 (TGG), was identified (W258X). In one patient, the C to T transition within exon 3, which changes threonine at codon 217 to methionine (T217 M), and the W258X mutation were found (compound heterozygote). Thus, among 12 mutational alleles in six patients, 11 were the W258 X mutation (92%). Family members with the heterozygous W258X mutation (carriers) show relatively low levels of serum urate. The present study demonstrates that homozygous W258X mutation is the predominant genetic cause of idiopathic renal hypouricemia in Japanese patients.

Metabolic findings after colocystoplasty in children.

OBJECTIVES: To investigate whether colocystoplasty has resulted in metabolic changes in the growing child during long-term follow-up according to whether cecum with ascending or sigmoid colon was used. METHODS: Twenty-eight patients (mean age at surgery 11 years) were included in the study and divided into two groups: group 1, cystoplasty with cecum and ascending colon (12 patients) and group 2, sigmoid cystoplasty (16 patients). Patients' linear growth, body mass index, and the following parameters were estimated before surgery and at 3, 6, and 12 months, and then yearly after surgery: blood and urine electrolytes (sodium, potassium, chloride, calcium, phosphorus, magnesium), creatinine, urea, blood gases, blood pH, urine pH, and blood alkaline phosphatase (ALP). All the data were statistically analyzed. RESULTS: In group 1, the blood ALP increased significantly (P = 0.026) during follow-up. Severe metabolic acidosis with or without hyperchloremia was found in 7 patients. In group 2, the serum sodium and serum calcium levels decreased significantly (P = 0.014 and P = 0.003, respectively); however, the blood ALP, urine sodium, and urine phosphorus levels increased significantly (P = 0.033, P = 0.027, and P = 0.026, respectively) during follow-up. A statistically significant decrease in blood pH (P = 0.022) was found after surgery. Severe metabolic acidosis with or without hyperchloremia was detected in 5 patients. The average linear growth decreased significantly (P = 0.001 and P = 0.016, respectively) 1 and 2 years postoperatively. CONCLUSIONS: The statistically significant increase in blood ALP and decrease in serum calcium indicate bone demineralization after colocystoplasty. Our investigations in children suggest that bone demineralization is more frequent after sigmoid cystoplasty than after the use of cecum and ascending colon.