A Single-Point Insulin Sensitivity Estimator (SPISE) of 5.4 is a good predictor of both metabolic syndrome and insulin resistance in adolescents with obesity.

Background: The Single-Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity estimated using BMI and triglycerides and high-density lipoprotein cholesterol. We assessed the accuracy of SPISE to screen obesity-related cardiometabolic risk in children and adolescents. Method: Cross-sectional validation study for a screening test in a sample of n=725 children and adolescents from an obesity clinic. Weight, height, waist circumference, blood arterial pressure, lipid profile, glucose, insulin and Tanner stage were measured. BMI, BMI for-age-and sex (BAZ), and HOMA-IR were estimated. HOMA-IR values ≥2.1 and ≥3.3 were considered IR in Tanner I-II, ≥3.3 for Tanner III-IV and ≥2.6 for Tanner V, respectively. Metabolic Syndrome (MetS) was diagnosed with the Cook phenotype. SPISE was estimated according to the following algorithm: [600* HDL^0.185/(TG^0.2* BMI^1.338)]. The optimal SPISE cut points for IR and MetS prediction were determined by ROC curve analysis. Results: In prepubertal obese patients (9.2 ± 2.1y; 18.4% males), the prevalence of IR and MetS was 28.2% y 46.9%, respectively; 58% had severe obesity (BAZ ≥4 SD). In pubertal obese patients (12.6 ± 1.8y; 57% males), the prevalence of IR and MetS was 34.1% and 55.3%, respectively; 34% had severe obesity. In prepubertal children, a SPISE of 6.3 showed the highest sensitivity (73.2%) and specificity (80%) to screen individuals with IR (AUC: 0.80; LR +: 3.3). Likewise, a SPISE of 5.7 got the highest sensitivity (82.6%) and specificity (86.1%) to screen patients with MetS (AUC: 0.87; LR +: 5.4). In pubertal patients, a SPISE of 5.4 showed the highest sensitivity and specificity to screen children and adolescents with both IR (Sn: 76.1%; Sp: 77.5%; AUC: 0.8; LR +: 3.1) and MetS (Sn: 90.4%; Sp: 76.1%; AUC: 0.90; LR +: 3.5). Conclusion: In children and adolescents with obesity, SPISE has good or very good performance in predicting IR and MetS. SPISE may be considered a relatively simple and low-cost diagnosis tool that can be helpful to identify patients with greater biological risk. In adolescents with obesity, the same cut point allows identification of those at higher risk of both IR and MetS.

El Estimador de Sensibilidad Insulínica de Punto Único (SPISE) supera a marcadores antropométricos de uso rutinario en la pesquisa de riesgo cardiometabólico asociado a obesidad: un estudio en adolescentes de la Región Metropolitana / The single Point Insulin Sensitivity Estimator (SPISE) outperforms routine anthropometric markers in the screening of obesity-related cardiometabolic risk: a study in adolescents from the Metropolitan Region

El Estimador de Sensibilidad a la Insulina de Punto Único (SPISE) es un biomarcador de sensibilidad a la insulina comparable al Índice de Matsuda. Se estima utilizando el IMC y los niveles de triglicéridos y HDL. El objetivo de este estudio fue comparar el rendimiento diagnóstico de SPISE con el de otros marcadores antropométricos de uso rutinario, como el IMC y la relación cintura | talla, en la pesquisa de insulinoresistencia (IR) y Síndrome Metabólico (MetS) en una muestra de 901 adolescentes de 11 a 16 años. En todos ellos se midió peso, talla, cintura, presión arterial, perfil lipídico, insulina y glicemia. La IR se diagnosticó con el HOMA-IR y el MetS con el criterio de Cook. Un zIMC ≥2.0 DE, un índice cintura/ talla ≥0.54 y un SPISE ≤ 5.4 fueron los puntos de corte utilizados para evaluar el rendimiento de estos marcadores en el diagnóstico de IR y MetS. No hubo diferencias por sexo en la prevalencia de obesidad, IR y MetS. Tanto en hombre como en mujeres, SPISE mostro una mejor capacidad para predecir el MetS (AUC: 0.95 y 0.89, respectivamente) e IR (AUC: 0.83 y 0.79, respectivamente) comparado con el rendimiento diagnóstico de la relación cintura | talla y el IMC-z. De igual manera, el SPISE mostro una mayor sensibilidad para identificar a los portadores de MetS e IR (96% y 75% en varones y 81% y 67% en mujeres, respectivamente). SPISE mostró una mejor capacidad para identificar el riesgo cardiometabólico asociado a la malnutrición por exceso al compararlo con otros indicadores de uso frecuente en clínica. Un índice de SPISE ≤5.4 fue un mejor predictor de MetS e IR que un IMC ≥2.0 DE y una relación cintura | talla ≥0.54.

The Single Point Insulin Sensitivity Estimator (SPISE) is a biomarker of insulin sensitivity comparable to the Matsuda Index. It is estimated using data on BMI, TG, and HDL. We aim to compare the diagnostic performance of SPISE with other routinely used anthropometric markers, such as BMI and waist-to-height ratio, in diagnosing insulin resistance (IR) and Metabolic Syndrome (MetS) in adolescents from 11 to 16 years. Weight, height, waist, blood pressure, lipid profile, insulin, and glycemia were measured. IR was diagnosed with the HOMA-IR and the MetS with the Cook criteria. A BMIz ≥2.0 SD, a waist-to-height ratio ≥0.54, and a SPISE ≤ 5.4 were the cut-off points used for diagnosing IR and MetS. There were no sex differences in the prevalence of obesity, IR, and MetS. In both males and females, SPISE showed a better ability to predict MetS (AUC: 0.95 and 0.89, respectively) and IR (AUC: 0.83 and 0.79, respectively) compared to the waist-to-height ratio and BMI-z. Similarly, SPISE showed greater sensitivity to identify adolescents with MetS and IR (96% and 75% in men and 81% and 67% in women, respectively) than the waist-to-height ratio and BMI-z. SPISE performed better in identifying obesity-related cardiometabolic risk than other frequently used clinical indicators. A SPISE index ≤5.4 was a better predictor of MetS and RI than a BMI ≥2.0 SD and a waist-to-height ratio ≥0.54.

Lessons from a 30 year follow-up of monozygotic twins with discordant phenotype due to a ring 13 chromosomal mosaicism in one of them.

At the 43rd annual meeting of the ASHG in 1993, the senior author reported monozygotic twins with discordant phenotype due to a ring 13 chromosomal mosaic syndrome in one of them. Her major manifestations included: intrauterine growth restriction (IUGR), failure to thrive (FTT), delayed developmental milestones/intellectual disability (DDM/ID), left hemihypoplasia of her body with leg length discrepancy, left profound deafness due to inner ear malformation, telecanthus, dental anomalies mainly on the left side, congenital torticollis due to Klippel-Feil anomaly, 13 ribs, scoliosis, dislocation of the left hip, and distinctive left hand and feet. A blood karyotype at age 31/2 was normal. Silver-Russell syndrome was initially suspected; however, at age 4, a karyotype on skin fibroblasts showed a ring 13 chromosomal mosaicism, 46,XX,15s+/46,XX,-13,+r(13),15s+, with a higher frequency on the left side of the body. Since then, we have been involved in the management of this patient for 30 years. This has ultimately allowed us to compare her achievements with her normal monozygotic twin. In this long term follow-up, we want to emphasize the importance of: (a) early recognition of genetic syndromes, especially of mosaicisms, and of early intervention programs, (b) the involvement of different specialists in the management of patients with MCA, and (c) mentioning how familial and socioeconomic issues may limit or enhance the full potential of patients with some genetic disorders.

A Deletion of More than 800 kb Is the Most Recurrent Mutation in Chilean Patients with SHOX Gene Defects.

BACKGROUND: Deletions in the SHOX gene are the most frequent genetic cause of Leri-Weill syndrome and Langer mesomelic dysplasia, which are also present in idiopathic short stature. AIM: To describe the molecular and clinical findings observed in 23 of 45 non-consanguineous Chilean patients with different phenotypes related to SHOX deficiency. METHODS: Multiplex ligation-dependent probe amplification was used to detect the deletions; the SHOX coding region and deletion-flanking areas were sequenced to identify point mutations and single-nucleotide polymorphisms (SNPs). RESULTS: The main genetic defects identified in 21 patients consisted of deletions; one of them, a large deletion of >800 kb, was found in 8 patients. Also, a smaller deletion of >350 kb was observed in 4 patients. Although we could not precisely determine the deletion breakpoint, we were able to identify a common haplotype in 7 of the 8 patients with the larger deletion based on 22 informative SNPs. CONCLUSION: These results suggest that the large deletion-bearing allele has a common ancestor and was either introduced by European immigrants or had originated in our Amerindian population. This study allowed us to identify one recurrent deletion in Chilean patients; also, it contributed to expanding our knowledge about the genetic background of our population.

Síndrome de Sengers: comunicación de dos casos en Chile / Sengers syndrome: report of two cases in chile

El Síndrome de Sengers es una enfermedad mitocondrial autosómica recesiva, producida por mutación del gen de la Acil-Glicerol Kinasa (AGK), recientemente descubierto. Se caracteriza por cataratas congénitas bilaterales, miocardiopatía hipertrófica y acidosis láctica. Puede tener miopatía esquelética leve, intolerancia al ejercicio y desarrollo mental normal. Los pacientes fallecen tempranamente debido a falla cardíaca. Dada la alta letalidad, lo infrecuente de este síndrome y la presencia de un diagnóstico confirmado, se presenta el caso clínico de 2 hermanos chilenos, fallecidos por la enfermedad, que se presentaron con el cuadro característico de cataratas congénitas bilaterales, miocardiopa-tía hipertrófica y acidosis láctica. El mayor, se operó las cataratas a los 4 meses de edad y falleció a la edad de 13 meses debido a falla cardíaca severa refractaria y falla orgánica múltiple, descompensado por una infección respiratoria. El menor se diagnosticó a los 3 meses de edad y se le confirmó la mutación del gen de AGK en Alemania. Se decidió no operarlo de las cataratas dado el mal pronóstico vital. Presentó progresión de la miocardiopatía hipertrófica y falleció súbitamente a los 8 meses de edad.

Senger's Syndrome is a recessive autosomal mitochondrial disease due to a recently discovered mutation of the Acyl-Glycerol Kinase (AGK) gen,. It is characterized by congenital bilateral cataracts, progressive hypertrophic cardiomyopathy and lactic acidosis. It may present skeletal myopathy, exercise intolerance and usually normal mental development. Patients die early in life due to heart failure. The clinical cases of two brothers with a confirmed diagnosis of Senger's syndrome are reported. The older brother was operated on for cataracts at the age of 4 months and he died when he was 13 months old due to severe refractory heart failure and multi-organ failure, decompensated by a respiratory infection. The younger brother was diagnosed at 3 month of age and the AGK gene mutation was confirmed in Germany. Cataracts were not operated on due to the the patient's extremely poor prognosis. He had progressive hypertrophic cardiomyopathy and died suddenly at 8 month of age.

VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study.

Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80% of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

VEGFA polymorphisms and cardiovascular anomalies in 22q11 microdeletion syndrome: a case-control and family-based study

Microdeletion 22q11 in humans causes velocardiofacial and DiGeorge syndromes. Most patients share a common 3Mb deletion, but the clinical manifestations are very heterogeneous. Congenital heart disease is present in 50-80 percent of patients and is a significant cause of morbidity and mortality. The phenotypic variability suggests the presence of modifiers. Polymorphisms in the VEGFA gene, coding for the vascular endothelial growth factor A, have been associated with non-syndromic congenital heart disease, as well as with the presence of cardiovascular anomalies in patients with microdeletion 22q11. We evaluated the association of VEGFA polymorphisms c.-2578C>A (rs699947), c.-1154G>A (rs1570360) and c.-634C>G (rs2010963) with congenital heart disease in Chilean patients with microdeletion 22q11. The study was performed using case-control and family-based association designs. We evaluated 122 patients with microdeletion 22q11 and known anatomy of the heart and great vessels, and their parents. Half the patients had congenital heart disease. We obtained no evidence of association by either method of analysis. Our results provide further evidence of the incomplete penetrance of the cardiovascular phenotype of microdeletion 22ql 1, but do not support association between VEGFA promoter polymorphisms and the presence of congenital heart disease in Chilean patients with this syndrome.

Incidencia de cardiopatías congénitas en nacidos vivos / Incidence of congenital heart diseases in live born infants

De un total de 7.370 nacidos vivos durante 1983 en un hospital metropolitano de Santiago, 730 fueron referidos para estudio en la Unidad de Cardiología pediátrica, encontrando 101 pacientes con cardiopatías congénitas, lo que representa una incidencia de 13,70 por mil nacidos vivos. La mayoría de ellas (74%) fueron pesquisadas durante el primer mes de vida, el resto, en edades mayores, a lo largo de un período de seguimiento de 20 a 32 semanas. La presencia de soplos anorgánicos se detectó en 68 de 730 niños referidos a cardiología, desapareciendo en 30 de ellos (45%) en los controles sucesivos. De los 22 síndromes genéticos detectados en la población estudiada, 14 correspondieron a síndrome de Down y 11 de ellos (79%) tenían cardiopatías congénitas. Se encontraron malformaciones asociadas en 15 de los 101 (14,8%) pacientes con cardiopatías congénitas. Durante el primer año de vida, fallecieron 17 de los 101 pacientes: letalidad 168 por mil. La tasa descrita para cardiopatías congénitas en este estudio es la primera que se comunica en nuestro medio, y es mayor que la descrita en el extranjero. La distribución porcentual relativa concuerda en general con la descrita por otros autores

Uso profiláctico de antibióticos en cateterismo umbilical en recién nacidos / Prophylactic use of antibiotics in umbilical catheterism in newborn infants

Para estimar la utilidad de los antibióticos en la prevención de septicemias en RN sometidos a exanguineotransfusión o globuloforesis mediante cateterismo umbilical, se estudiaron 29 RN de término, en el Hospital Regional de Temuco, distribuidos al azar en dos grupos, uno que recibió antibióticos en la forma habitual y otro no. Se practicaron hemogramas y hemocultivos al tercer día del procedimiento en ambos grupos. Se encontraron 5 hemocultivos positivos entre 15 RN con antibióticos y 5 entre 14 sin antibióticos. Todos los hemocultivos se consideraron contaminados porque no se acompañaron de signos clínicos ni hematológicos sugerentes de septicemia. Se concluye que en nuestro medio de trabajo no está indicado el uso profiláctico de antobióticos en los RN de término, sin otra mortalidad, que se somenten a cateterismo umbilical