A Novel Mutation in the INSR Gene Causes Severe Insulin Resistance and Rabson-Mendenhall Syndrome in a Paraguayan Patient.

Rabson-Mendenhall syndrome (RMS) is a rare autosomal recessive disorder characterized by severe insulin resistance, resulting in early-onset diabetes mellitus. We report the first case of RMS in a Paraguayan patient. The patient is a 6-year-old girl who presented with hypertrichosis, acanthosis nigricans, nephrocalcinosis, and elevated levels of glucose and insulin that served as diagnostic indicators for RMS. Genetic testing by next-generation sequencing (NGS) revealed two pathogenic variants in exons 2 and 19 of the INSR gene: c.332G>T (p.Gly111Val) and c.3485C>T (p.Ala1162Val), in combined heterozygosis. The novel INSR c. 332G>T variant leads to the substitution of glycine to valine at position 111 in the protein, and multiple in silico software programs predicted it as pathogenic. The c.3485C>T variant leads to the substitution of alanine to valine at position 1162 in the protein previously described for insulin resistance and RMS. The management of RMS is particularly challenging in children, and the use of metformin is often limited by its side effects. The patient was managed with nutritional measures due to the early age of onset. This report expands the knowledge of RMS to the Paraguayan population and adds a novel pathogenic variant to the existing literature.

Consolidation of the Neonatal Screening Program as a Public Health Program in Paraguay

Abstract In Paraguay, neonatal screening for congenital hypothyroidism (CH) and phenylketonuria (PKU) started in October 1999, in 2005 cystic fibrosis (CF) was selectively incorporated. The National Program for Neonatal Screening has a centralized laboratory that encompasses 1.132 Sample Collecting Sites (SCS) distributed in the 18 Health Regions, with over 80% coverage of live births; the incidence of CH being 1:2.060, HPA/PKU 1:6.328 and CF 1:5.671 newborns. The newborn screening program headed by the Ministry of Public Health and Social Welfare in Paraguay has been consolidated itself as a public health program. This publication describes the historic 20-year process, the strategies and activities carried out as well as the results and achievements, among which it is important to point out the achievement of newborns screening laws that make mandatory to detect, diagnose and treat those affected, as well as the human resources committed to newborn screening.

Síndrome de McCune-Albright. Reporte de un caso / McCune-Albright syndrome: a Case Report

El Síndrome de McCune-Albright (SMA) es una rara entidad que se caracteriza por displasia fibrosa ósea poliostótica, lesiones cutáneas hiperpigmentadas y endocrinopatías, la más frecuente es la pubertad precoz y sobre todo en niñas. Presentamos el caso de una paciente de sexo femenino de 5 años de edad, que se interna por fractura patológica del fémur derecho, constatándose lesiones líticas en fémur contralateral, pelvis, tórax y calota; manchas café con leche en regiones del tórax anterior, perineal y dorsolumbar; Tanner 2 mamario y púbico, con antecedente de sangrado vaginal en 2 oportunidades 1 mes antes; y con Rx de muñeca izquierda compatible con edad ósea de 9 años; además de microadenoma hipofisiario. El SMA resulta de mutaciones esporádicas somáticas postcigóticas en el gen que codifica la subunidad α de la proteína Gs (GNAS1). Esta proteína actúa en la transducción de señales mediante la unión a la adenil-ciclasa productora de adenosín monofosfato cíclico (AMPc). Es importante conocer esta asociación de signos a fin de obtener un diagnóstico precoz y manejo adecuado .

McCune-Albright syndrome (MAS)isa rare disease characterized by poly ostotic fibrous dysplasia of bone, hyperpigmented skin lesions, and endocrinopathies, most commonly precocious puberty, and especially in girls. We presented the case of a female patient aged 5years hospitalized for pathological fracture of the right femur with findings of lytic lesions of the contralateral femur pelvis, thorax, and calvarium, and café-au-lait spots of the anterior, perineal, and dorsolumbar thorax; Tanner stage 2 breasts and pubes, a history of vaginal bleeding on two occasionsone monthearlier, left-wrist X-ray compatible with abone age of 9years and pituitary microadenoma. MAS is caused by sporadic postzygotic somatic mutations of the gene that codifies the alpha subunit of the G(s) protein (GNAS1). This protein acts in the transduction of signals by binding with cyclic-adenosine-monophosphate (cAMP) producing adenylate cyclase. It is important to beaware of this group of associated signs in order to achiev e early diagnosis and appropriate treatment.

Valor de referencia de la hormona estimulante de la tiroides (TSH) por fluoroinmunoensayo en neonatos del Paraguay / The reference value of thyroid stimulating hormone (TSH) determined by fluoroimmunoassay in Paraguayan newborns

El término de valores de referencia es un concepto ampliamente aceptado y aplicado internacionalmente y puede ser expresado como el establecimiento y uso de datos relevantes para lainterpretación de observaciones médicas. La hormona estimulante de la tiroides (TSH), juega un papel determinante en la detección temprana de una de las pocas causas prevenibles de retardo mental, el hipotiroidismo congénito. Los valores de referencia utilizados en el PPFQRM han sido establecidos según la recomendación del valor dado por la prueba comercialutilizada (<9 Normal, 9-18 borderline, >18μU/ml hipotiroidismo), en muestras de sangre en papel de filtro de reciénnacidos entre 2 a 6 días de vida.Se realizó un estudio observacional de corte transverso con 20.168 muestras de sangre seca de recién nacidos de 1 a 7 días de vida a término, para determinar el valor de referencia de la TSH de la población de RN en el Paraguay, utilizándose las medidas de tendencia central y de dispersión: media, mediana, percentiles y ladistribución de frecuencias a fin de caracterizar a la variable deinterés. El 22% de las muestras presentó valores de TSH entre0.01-1.0, 25% entre 1.1-2, 19% entre 2.1-3.0, 12% entre 3.1-4, 8% entre 4.1-5 y 14% mayor a 5 μU/ml. Se encontraron los siguientes valores de TSH; media: 2.74, mediana: 2.22, moda:0.01 y el desvió estándar: 2.14 μU/ml. Para el percentil 75: 3.26, el 95: 6.68 y el percentil 99: 9 μU/ml. En base a estasobservaciones se confirma como punto de corte un valor de TSH igual a 10 μU/ml.

The term “reference values" is widely accepted and applied internationally and can be expressed as the establishment and use of data relevant to the interpretation of medical observations.Thyroid stimulating hormone (TSH) plays a role in early detection of one of the few preventable causes of mentalretardation, congenital hypothyroidism. The reference values used in the program for prevention of cystic fibrosis and mental retardation (PPFQRM) were those recommended by the commercial test used (<9 Normal, 9-18 borderline, >18 ìU/mL hypothyroidism) using filter paper with blood samples from newborns at 2-6 days of life. We performed a cross-sectional, observational study with 20,168 dried blood samples from fullterm newborns at 1-7 days of life to determine the reference value for TSH in the NB population of Paraguay using themeasures of central tendency and dispersion: mean, median, percentiles, and frequency distribution in order to describe the variable under study. A TSH of between 0.01--1.0 μU/ml wasfound in 22% of samples, 1.1—2 μU/ml in 25% of samples, from 2.1--3.0 μU/ml in 19%, between 3.1—4 μU/ml in 12%, from 4.1—5 μU/ml in 8%, and more than 5 μU/ml in 14%. TSH valuesfound were: mean: 2.74, median: 2.22, mode: 0.01, and standard deviation was 2.14 μU/ml. For the 75th percentile: 3.26 μU/ml; 95th: 6.68 μU/ml; and 99th: 9 μU/ml. Based on these observations a cutoff point for TSH was confirmed equivalent to 10 μU/ml.

Incidencia de hipotiroidismo congénito en 14 regiones sanitarias de Paraguay / Incidence of congenital hypothyroidism in 14 health regions of Paraguay

El Hipotiroidismo Congénito, una de las causas tratables más comunes de retardo mental, ocurre en aproximadamente uno en 3000 recién nacidos. Se investiga la incidencia del hipotiroidismo congénito en Paraguay,país considerado endémico para los Desordenes por Deficiencia de Yodo.