Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery.

BACKGROUND: The electrocardiogram is the most widely used test to assess cardiovascular risk during the preoperative period. The objective of the present study is to evaluate the incidence of electrocardiographic alterations in the general population scheduled for non-cardiac surgery and to determine if the age greater than or equal to 65 years or the revised cardiac risk index ≥1 represent a risk factor for presenting these alterations. MATERIAL AND METHODS: Over a period of one month, all preoperative electrocardiograms (ECG) from the anesthesia clinic were analyzed. Various epidemiological data were collected and the revised cardiac risk index was calculated. Major alterations were defined as those requiring Cardiology follow-up. RESULTS: 476 patients were recruited, of whom 40.8% were ≥65 years, 32.6% had HTN, 14.4% DM and 27.9% dyslipidemia. 16.16% of the patients had a Lee Index ≥1. Of the entire sample, 80.5% had a normal ECG, 6.5% minor alterations and 13.0% major alterations. In the multivariate analysis, age ≥65 years and the presence of HTN were shown as independent risk factors for presenting alterations in the total and major ECG. The Lee index ≥1 was not associated with an increased risk of electrocardiographic abnormalities. CONCLUSIONS: Patients ≥65 years old and those with HTN are at greater risk of presenting major electrocardiographic abnormalities, so we recommend including the ECG as a routine diagnostic test in the preoperative period of non-cardiac surgery.

Incidencia de alteraciones electrocardiográficas en el preoperatorio de cirugía no cardiaca / Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery

Antecedentes: El electrocardiograma es la prueba más utilizada para evaluar el riesgo cardiovascular durante el periodo preoperatorio. El objetivo del presente estudio es evaluar la incidencia de alteraciones electrocardiográficas en la población general programada para cirugía no cardiaca y determinar si la edad ≥ 65 años o el índice de riesgo cardiaco revisado ≥ 1 suponen un factor de riesgo para presentar dichas alteraciones. Material y métodos: Durante un periodo de un mes se analizaron todos los electrocardiogramas (ECG) preoperatorios de la consulta de anestesia. Se recogieron datos epidemiológicos y se calculó el índice de riesgo cardiaco revisado. Se definieron como alteraciones electrocardiográficas mayores aquellas que precisaban seguimiento por Cardiología. Resultados: Se reclutaron 476 pacientes, de los cuales 40,8% eran ≥ 65 años, 32,6% tenían HTA, 14,4% DM y 27,9% dislipemia. Un 16,16% de los pacientes tuvieron un índice de Lee ≥ 1.El 80,5% de los pacientes presentaban un ECG normal, el 6,5% alteraciones menores y el 13%, alteraciones mayores. En el análisis multivariante, la edad ≥ 65 años y la presencia de HTA se mostraron como factores de riesgo independiente para presentar alteraciones en el ECG totales y mayores.El índice de Lee ≥ 1 no se asoció con un mayor riesgo de alteraciones electrocardiográficas.ConclusiónLos pacientes ≥ 65 años o aquellos con HTA tienen mayor riesgo de presentar alteraciones electrocardiográficas mayores, por lo que recomendamos incluir en estos el ECG como prueba diagnóstica preoperatoria de rutina en cirugía no cardiaca.(AU)

BackgroundThe electrocardiogram is the most widely used test to assess cardiovascular risk during the preoperative period.The objective of the present study is to evaluate the incidence of electrocardiographic alterations in the general population scheduled for non-cardiac surgery and to determine if the age greater than or equal to 65 years or the revised cardiac risk index ≥ 1 represent a risk factor for presenting these alterations.Material and methods: Over a period of one month, all preoperative electrocardiograms (ECG) from the anesthesia clinic were analyzed. Various epidemiological data were collected and the revised cardiac risk index was calculated. Major alterations were defined as those requiring Cardiology follow-up.Results: 476 patients were recruited, of whom 40.8% were ≥ 65 years, 32.6% had HTN, 14.4% DM and 27.9% dyslipidemia. 16.16% of the patients had a Lee Index ≥ 1.Of the entire sample, 80.5% had a normal ECG, 6.5% minor alterations and 13.0% major alterations. In the multivariate analysis, age ≥ 65 years and the presence of HTN were shown as independent risk factors for presenting alterations in the total and major ECG.The Lee index ≥ 1 was not associated with an increased risk of electrocardiographic abnormalities.Conclusions: Patients ≥ 65 years old and those with HTN are at greater risk of presenting major electrocardiographic abnormalities, so we recommend including the ECG as a routine diagnostic test in the preoperative period of non-cardiac surgery.(AU)

Incidence of electrocardiographic alterations in the preoperative period of non-cardiac surgery. / Incidencia de alteraciones electrocardiográficas en el preoperatorio de cirugía no cardiaca.

BACKGROUND: The electrocardiogram is the most widely used test to assess cardiovascular risk during the preoperative period. The objective of the present study is to evaluate the incidence of electrocardiographic alterations in the general population scheduled for non-cardiac surgery and to determine if the age greater than or equal to 65 years or the revised cardiac risk index ≥ 1 represent a risk factor for presenting these alterations. MATERIAL AND METHODS: Over a period of one month, all preoperative electrocardiograms (ECG) from the anesthesia clinic were analyzed. Various epidemiological data were collected and the revised cardiac risk index was calculated. Major alterations were defined as those requiring Cardiology follow-up. RESULTS: 476 patients were recruited, of whom 40.8% were ≥ 65 years, 32.6% had HTN, 14.4% DM and 27.9% dyslipidemia. 16.16% of the patients had a Lee Index ≥ 1. Of the entire sample, 80.5% had a normal ECG, 6.5% minor alterations and 13.0% major alterations. In the multivariate analysis, age ≥ 65 years and the presence of HTN were shown as independent risk factors for presenting alterations in the total and major ECG. The Lee index ≥ 1 was not associated with an increased risk of electrocardiographic abnormalities. CONCLUSIONS: Patients ≥ 65 years old and those with HTN are at greater risk of presenting major electrocardiographic abnormalities, so we recommend including the ECG as a routine diagnostic test in the preoperative period of non-cardiac surgery.

Unapparent hypoxanthine-guanine phosphoribosyltransferase deficiency.

Complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity causes Lesch Nyhan disease (LND), characterized by hyperuricemia, severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit and self-injurious behavior. Partial HPRT deficiency is present in patients with Lesch-Nyhan variant (LNV), who present with HPRT-related gout and a variable degree of neurological involvement. The diagnosis of HPRT deficiency relies on clinical, biochemical, enzymatic and molecular data. Patients with HPRT deficiency present low or undetectable HPRT activity in hemolysates, with increased adenine phosphoribosyltransferase (APRT) activity. We present a 9-year-old boy who experienced an episode of macroscopic hematuria with dysuria and left flank pain. He presented hyperuricemia and hyperuricosuria. HPRT and APRT activities were both normal in hemolysate; however, HPRT activity assayed in intact erythrocytes was 50% of control levels. A new missense point mutation c.424 A>G (T142A) was found in the HPRT1 gene. The apparent Michaelis constant (Km) for 5-phosphoribosyl-pyrophosphate assayed in patient hemolysate was 20-fold of control levels. In conclusion, we report a patient with HPRT deficiency who presented with both normal HPRT and APRT activity in hemolysate, in which the enzyme activity determined in intact erythrocytes was of diagnostic utility.

Ultrasonography in the diagnosis of asymptomatic hyperuricemia and gout.

Sonography has detected urate deposits in 34%-42% of the patients with asymptomatic hyperuricemia. This may prompt reclassification of asymptomatic hyperuricemia into "asymptomatic gout" and consideration of urate lowering therapy (ULT) to resolve urate deposits. In patients with gout and no visible tophi, sonography has detected urate deposits in half of the patients. This may allow diagnosing "tophaceous gout" and influencing the serum urate target level, prophylaxis to avoid acute gout flares during ULT, and clinical follow-up. Current accessibility to sonography may better classify patients with hyperuricemia and gout and contribute to delineate therapeutic objectives and clinical guidance.

A review of the implication of hypoxanthine excess in the physiopathology of Lesch-Nyhan disease.

Lesch-Nyhan disease is caused by HGprt deficiency, however, the mechanism by which enzyme deficiency leads to the severe neurological manifestations is still unknown. We hypothesized that hypoxanthine excess leads, directly or indirectly, through its action in adenosine transport, to aberrations in neuronal development. We found that hypoxanthine diminishes adenosine transport and enhances stimulation of adenosine receptors. These effects cause an imbalance between adenosine, dopamine, and serotonin receptors in HGprt deficient cells, and cells differentiated with hypoxanthine showed an increase in dopamine, adenosine and serotonin receptors expression. Hypoxanthine deregulates early neuronal differentiation increasing WNT4 and EN1 gene expression.

Hypoxanthine deregulates genes involved in early neuronal development. Implications in Lesch-Nyhan disease pathogenesis.

Neurological manifestations in Lesch-Nyhan disease (LND) are attributed to the effect of hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency on the nervous system development. HPRT deficiency causes the excretion of increased amounts of hypoxanthine into the extracellular medium and we hypothesized that HPRT deficiency related to hypoxanthine excess may then lead, directly or indirectly, to transcriptional aberrations in a variety of genes essential for the function and development of striatal progenitor cells. We have examined the effect of hypoxanthine excess on the differentiation of neurons in the well-established human NTERA-2 cl.D1 (NT2/D1) embryonic carcinoma neurogenesis model. NT2/D1 cells differentiate along neuroectodermal lineages after exposure to retinoic acid (RA). Hypoxanthine effects on RA-differentiation were examined by the changes on the expression of various transcription factor genes essential to neuronal differentiation and by the changes in tyrosine hydroxylase (TH), dopamine, adenosine and serotonin receptors (DRD, ADORA, HTR). We report that hypoxanthine excess deregulate WNT4, from Wnt/ß-catenin pathway, and engrailed homeobox 1 gene and increased TH and dopamine DRD1, adenosine ADORA2A and serotonin HTR7 receptors, whose over expression characterize early neuro-developmental processes.

De la mutación al fenotipo; variabilidad clínica en la enfermedad de Lesch-Nyhan. El papel de la epigenética / From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics

La enfermedad de Lesch-Nyhan es una enfermedad genética considerada dentro de las enfermedades raras, caracterizada por un déficit en la función de la enzima hipoxantina-guanina fosforribosil transferasa (HPRT). Los pacientes afectados presentan hiperuricemia, trastornos motores, retraso mental y, en los casos más graves, automutilaciones. Las manifestaciones clínicas dependen de la actividad enzimática de la HPRT, que clásicamente se vincula al tipo de alteración en el gen HPRT, habiéndose encontrado más de 400 mutaciones. En la actualidad uno de los aspectos controvertidos de la enfermedad es la relación existente entre el genotipo y el fenotipo, habiéndose descrito casos en ausencia de mutación (como el paciente que presentamos), así como familias que, a pesar de compartir un mismo defecto genético, muestran afectaciones con distinta gravedad. Los procesos epigenéticos, que modifican la expresión genética sin alterar la secuencia del ácido desoxirribonucleico (ADN), podrían explicar la variabilidad clínica observada en esta enfermedad (AU)

Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease (AU)

Fenofibrate increases serum creatinine in a patient with familial nephropathy associated to hyperuricemia.

BACKGROUND: Kidney function progressively deteriorates in patients with familial juvenile hyperuricemiac nephropathy (FJHN, OMIN 162000) and chronic renal disease is commonly associated to dyslipidemia. We report for the first time abrupt renal insufficiency in a patient with FJHN and hypertrygliceridemia following fenofibrate administration. CASE REPORT: A 53-year-old man was diagnosed clinically with FJHN at age 24 years which was subsequently confirmed by genotypic analysis of the UMOD gene at age 40 years. His mother and two brothers suffered the disease. At that time, renal size and function were normal, as was his blood pressure and serum lipids. At age 34 years, serum urate was 8.5 mg/dL and creatinine 1.7 mg/dL (GFR, 58 mL/min/1.73 m2). He was treated with allopurinol, losartan, and lovastatin. Serum TG levels ranged between 150 and 250 mg/dL. At age 52 years, serum urate was 4.1 mg/dL, creatinine 3.2 mg/dL, LDLc 99 mg/dL (atorvastatin 40 mg/d), and TG 275 mg/dL. Fenofibrate (160 mg/d) was added. One month later, serum creatinine increased to 4.2 mg/dL and TG decreased to 125 mg/dL. He did not complain of muscle pain, weakness, or changes in urinary frequency or color and rabdomyolysis was discarded. Fenofibrate was withheld and three months later serum creatinine decreased to baseline levels (3.2 mg/dL) and TG increased to 197 mg/dL. CONCLUSION: To our knowledge, this is the first patient with FJHN in whom fenofibrate administration was associated to a further impairment in renal function not attributable to rabdomyolysis.

HPRT deficiency in Spain: what have we learned in the past 30 years (1984-2013)?

Since 1984, we have diagnosed at the La Paz University Hospital, Madrid, Spain, 41 patients with hypoxanthine phosphoribosyltransferase (HPRT) activity deficiency. These patients belonged to 34 families. We have also performed molecular and enzymatic diagnosis in three patients from India, one from Belgium, and three from Colombia. About 1/3 of these patients were followed up at La Paz University Hospital at least every year. This fact has allowed us to examine the complete spectrum of HPRT deficiency as well as to perform a more accurate diagnosis and treatment. In the present review, we also summarized our studies on the basis of physiopathology of the neurological manifestation of Lesch Nyhan disease (LND).

From genotype to phenotype; clinical variability in Lesch-Nyhan disease. The role of epigenetics. / De la mutación al fenotipo; variabilidad clínica en la enfermedad de Lesch-Nyhan. El papel de la epigenética.

Lesch-Nyhan disease is a rare genetic disease characterized by a deficiency in the function of the enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT). Patients affected by this disease experience hyperuricemia, motor disorders, mental retardation and, in the most severe cases, self-mutilation. Its clinical manifestations depend on the enzymatic activity of HGPRT, which is classically linked to the type of alteration in the HGPRT gene. More than 400 mutations of this gene have been found. At present, one of the controversial aspects of the disease is the relationship between the genotype and phenotype; cases have been described lacking a mutation, such as the patient presented in this article, as well as families who despite sharing the same genetic defect show disorders with differing severity. Epigenetic processes, which modify the genetic expression without changing the sequence of the deoxyribonucleic acid (DNA), could explain the clinical variability observed in this disease.

Partial HPRT deficiency phenotype and incomplete splicing mutation.

Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of enzyme deficiency. The complete deficiency causes Lesch-Nyhan syndrome (LNS). Partial HPRT-deficient patients can show a variable degree of neurological manifestations. Both diseases have been associated with mutations in the HPRT1 gene. Documented mutations in HPRT deficiency show a high degree of heterogeneity in type and location within the gene. In fact, more than 300 disease-associated mutations have been described. Splice mutations accounts for more that 16% of HPRT mutations and in most cases cause a complete LNS phenotype. A 16 year-old boy consulted to La Paz University Hospital because of hyperuricemia (9.4 mg/dL). At age one year he was given a diagnosis of dystonic cerebral palsy. Although he usually employs a wheelchair, under certain circumstances, he is able to stand up and walk by himself. He has never showed self injurious behavior. This patient presented a splice mutation (NM_000194.2: c.552 -2 A > G) causing exon 5 exclusion. An exon-5 specific PCR was designed, and a minor amount of normally spliced HPRT mRNA was found. Normally spliced HPRT mRNA was quantified by real-time PCR in this patient, in control subjects, and in two Lesch Nyhan patient with splice mutations excluding exon 4 (patient B) and exon 8 (patient C) who had clinically a Lesch Nyhan disease phenotype. A minor amount of normally spliced HPRT mRNA was found in all the patients. No correlation was found between the percentage of the normally spliced HPRT mRNA and the phenotype. We conclude that the partial HPRT deficient phenotype of this patient can not be explained by the finding of a minor amount of normally splice HPRT mRNA. It is possible that the amount of normally splice mRNA vary among different tissues.

Methylation status of HPRT1 promoter in HPRT deficiency with normal coding region.

UNLABELLED: Lesch-Nyhan syndrome is an X-linked recessive inborn error of metabolism due to a complete deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity (OMIM 300322). Partial deficiency of HPRT (OMIM 300323) is characterized by the effects of excess uric acid synthesis and a continuum spectrum of neurological manifestations, without the manifestations of full-blown Lesch-Nyhan syndrome. Both diseases have been associated with mutations in the HPRT1 gene. We have described one Lesch-Nyhan patient and four partial HPRT deficient patients with a normal HPRT1 coding region. These patients showed markedly decreased HPRT mRNA expression, but no mutation in their genomic regulatory sequences from HPRT1 gene. In this study, we analyzed the promoter region methylation status of the HPRT1 gene in these five HPRT deficient patients. METHODS: DNA was bisulphite modified and a 620 bp fragment including 320 bp 5' to start codon was amplified and sequenced. The methylation status of 35 CpG island 5' to start codon and 28 CpG island 3' to start codon were investigated in male controls, female controls, patients, and the patient's mothers. Primer pairs were designed for methylated-specific and unmethylated-specific amplification and PCR was performed employing DNA bisulphite treated as template. RESULTS: No alterations in the methylation pattern of the HPRT1 promoter were found in the five HPRT deficient patients. CONCLUSIONS: The promoter region methylation status of these five HPRT deficient patients was similar to that of normal subjects. Thus, some other genetic alteration must explain a reduced enzyme activity with a normal gene coding region.

Metabolic syndrome characteristics in gout patients.

Gout is commonly associated with obesity, arterial hypertension, diabetes, and dyslipidemia. However, the prevalence of metabolic syndrome has not been widely recognized in patients with gout. We studied 41 patients (37 males) with primary gout to assess the prevalence and characteristics of the associated metabolic syndrome. Twenty-one patients with gout (51%) showed >or=3 criteria for the metabolic syndrome. Pathological conditions associated were obesity (21/41), high blood pressure (30/41), dyslipidemia (30/41), and fasting plasma glucose >or= 100 mg/dL (22/41). The most frequent triad was the presence of increased waist circumference, elevated fasting plasma glucose, and hypertension. Mean serum urate concentration did not differ significantly in gout patients with the metabolic syndrome (8.5 mg/dl) and without (8.1 mg/dl). Given the complications associated with metabolic syndrome, its diagnosis may determine the long-term treatment of patients with gout.

Harmonised framework for ecological risk assessment of sediments from ports and estuarine zones of North and South Atlantic.

This paper presents a harmonised framework of sediment quality assessment and dredging material characterisation for estuaries and port zones of North and South Atlantic. This framework, based on the weight-of-evidence approach, provides a structure and a process for conducting sediment/dredging material assessment that leads to a decision. The main structure consists of "step 1" (examination of available data); "step 2" (chemical characterisation and toxicity assessment); "decision 1" (any chemical level higher than reference values? are sediments toxic?); "step 3" (assessment of benthic community structure); "step 4" (integration of the results); "decision 2" (are sediments toxic or benthic community impaired?); "step 5" (construction of the decision matrix) and "decision 3" (is there environmental risk?). The sequence of assessments may be interrupted when the information obtained is judged to be sufficient for a correct characterisation of the risk posed by the sediments/dredging material. This framework brought novel features compared to other sediment/dredging material risk assessment frameworks: data integration through multivariate analysis allows the identification of which samples are toxic and/or related to impaired benthic communities; it also discriminates the chemicals responsible for negative biological effects; and the framework dispenses the use of a reference area. We demonstrated the successful application of this framework in different port and estuarine zones of the North (Gulf of Cádiz) and South Atlantic (Santos and Paranaguá Estuarine Systems).

Abnormal adenosine and dopamine receptor expression in lymphocytes of Lesch-Nyhan patients.

Self-injurious behavior is the most outstanding feature of Lesch-Nyhan syndrome and has recently been ascribed to an obsessive-compulsive behavior. Lesch-Nyhan syndrome results from the complete enzyme deficiency of hypoxanthine-guanine phosphoribosyl transferase (HPRT) but the link between abnormal purine metabolism and its neurological and behavioral manifestations remains largely unknown. Previous studies led us to hypothesize that adenosine and dopamine receptor expression could be altered in HPRT-deficient cells. To test this hypothesis, we examined mRNA expressions of adenosine (ADORA2A and ADORA2B) and dopamine receptors (DRD1 and DRD2 like), and dopamine transporter (DAT1) in peripheral blood lymphocytes (PBLs) from Lesch-Nyhan patients. We also examined the influence of hypoxanthine in these expressions. As compared to normal PBLs, both ADORA2A and DRD5 expression were abnormal in PBLs from Lesch-Nyhan patients. In contrast, DAT1 expression was similar to control values in HPRT deficient PBLs. These results indicate an abnormal adenosine and dopamine receptor expression in HPRT-deficient cells and suggest disrupted adenosine and dopamine neurotransmission may have a significant role in the pathogenesis of the neurological manifestations of Lesch-Nyhan syndrome.

Integrated sediment quality assessment in Paranaguá Estuarine System, Southern Brazil.

Sediment quality from Paranaguá Estuarine System (PES), a highly important port and ecological zone, was evaluated by assessing three lines of evidence: (1) sediment physical-chemical characteristics; (2) sediment toxicity (elutriates, sediment-water interface, and whole sediment); and (3) benthic community structure. Results revealed a gradient of increasing degradation of sediments (i.e. higher concentrations of trace metals, higher toxicity, and impoverishment of benthic community structure) towards inner PES. Data integration by principal component analysis (PCA) showed positive correlation between some contaminants (mainly As, Cr, Ni, and Pb) and toxicity in samples collected from stations located in upper estuary and one station placed away from contamination sources. Benthic community structure seems to be affected by both pollution and natural fine characteristics of the sediments, which reinforces the importance of a weight-of-evidence approach to evaluate sediments of PES.

Development of site-specific sediment quality guidelines for North and South Atlantic littoral zones: comparison against national and international sediment quality benchmarks.

We aimed to develop site-specific sediment quality guidelines (SQGs) for two estuarine and port zones in Southeastern Brazil (Santos Estuarine System and Paranaguá Estuarine System) and three in Southern Spain (Ría of Huelva, Bay of Cádiz, and Bay of Algeciras), and compare these values against national and traditionally used international benchmark values. Site-specific SQGs were derived based on sediment physical-chemical, toxicological, and benthic community data integrated through multivariate analysis. This technique allowed the identification of chemicals of concern and the establishment of effects range correlatively to individual concentrations of contaminants for each site of study. The results revealed that sediments from Santos channel, as well as inner portions of the SES, are considered highly polluted (exceeding SQGs-high) by metals, PAHs and PCBs. High pollution by PAHs and some metals was found in São Vicente channel. In PES, sediments from inner portions (proximities of the Ponta do Félix port's terminal and the Port of Paranaguá) are highly polluted by metals and PAHs, including one zone inside the limits of an environmental protection area. In Gulf of Cádiz, SQGs exceedences were found in Ria of Huelva (all analysed metals and PAHs), in the surroundings of the Port of Cádiz (Bay of Cádiz) (metals), and in Bay of Algeciras (Ni and PAHs). The site-specific SQGs derived in this study are more restricted than national SQGs applied in Brazil and Spain, as well as international guidelines. This finding confirms the importance of the development of site-specific SQGs to support the characterisation of sediments and dredged material. The use of the same methodology to derive SQGs in Brazilian and Spanish port zones confirmed the applicability of this technique with an international scope and provided a harmonised methodology for site-specific SQGs derivation.

The diagnosis of HPRT deficiency in the 21st century.

We have studied 36 patients with HPRT deficiency, 25 with Lesch-Nyhan syndrome and 11 with partial HPRT deficiency (grades 1 to 3). Patients diagnosed with HPRT deficiency have increased 50% since 2000. The most relevant recent advances have been made in molecular diagnosis. Nevertheless, enzyme determinations are still essential for the diagnosis of HPRT deficiency. Therapy for the neurological manifestations of HPRT deficiency has not advanced. Allopurinol remains the drug of choice to diminish uric acid overproduction, but the optimal allopurinol dose must be established in each patient to prevent xanthine or uric acid urolithiasis, a process aided by sequential determination of urinary oxypurines and uric acid.

Urinary guanidinoacetate and creatine levels in patients with HPRT deficiency.

Neurobehavioral manifestations of complete HPRT deficiency include severe action dystonia, choreathetosis, alteration of executive functions, and self-injurious behavior. Dystonic manifestations are also present in patients with partial HPRT deficiency. Pathophysiology of these manifestations is unknown. Guanidinoacetate is a neurotoxin implicated in certain dystonic syndromes. We have examined guanidinoacetate and creatine levels in urine from 11 HPRT deficient patients (9 with Lesch-Nyhan syndrome and 2 with partial deficiency). Urinary guanidinoacetate and creatine levels in HPRT deficient patients were within the normal range. Guanidinoactetate alteration does not seem to be implicated in the pathogenesis of the neurological disease associated with HPRT deficiency.