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.

Association of class II HLA alleles with susceptibility to develop immune-mediated diseases in Paraguayan patients.

Genetic and nongenetic factors are involved in the pathogenesis of immune-mediated inflammatory diseases (IMIDs). The best-known genetic factor for susceptibility to IMIDs is the human leukocyte antigen (HLA). The aim of the present study was to evaluate the association of HLA class II genes with the risk of systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and systemic sclerosis (SSc) in the Paraguayan population. We included 254 patients with IMIDs (101 SLE, 103 RA, and 50 SSc) and 50 healthy controls. The haplotypes of five genes corresponding to HLA class II genes and their relationship to the IMIDs studied were determined. Note that 84.6% were women, with a mean age of 43.4 ± 14 years. Among the associated HLA alleles, we found the previously identified risk factors in other populations like HLA-DRB1*03:01 and HLA-DRB1*14:02 for RA, as well as new ones not previously identified, such as DPA1*02:01 for SLE and, DB1*02:01 for RA and SSc. In the genetic association analysis, already known associations have been replicated, and unpublished associations have been identified in Paraguayan patients with IMIDs. This is the first genetic association study in Paraguayan patients with IMIDs.

The burden of venipuncture pain in neonatal intensive care units: EPIPPAIN 2, a prospective observational study.

BACKGROUND: Newborns in intensive care units (ICUs) undergo numerous painful procedures including venipunctures. Skin-breaking procedures have been associated with adverse neurodevelopment long-term effects in very preterm neonates. The venipuncture frequency and its real bedside pain management treatment are not well known in this setting. OBJECTIVES: To describe venipuncture frequency, its pain intensity, and the analgesic approach in ICU newborns; to determine the factors associated with the lack of preprocedural analgesia and with a high pain score during venipuncture. DESIGN: Further analysis of EPIPPAIN 2 (Epidemiology of Procedural Pain In Neonates), which is a descriptive prospective epidemiologic study. SETTING: All 16 neonatal and pediatric ICUs in the Paris region in France. PARTICIPANTS: All newborns in the ICU with a maximum corrected age under 45 weeks of gestation on admission who had at least one venipuncture during the study period. METHODS: Data on all venipunctures, their pain score assessed with the DAN scale and their corresponding analgesic therapies were prospectively collected. The inclusion period lasted six weeks, from June 2, 2011, to July 12, 2011. Newborns were followed from their admission to the 14th day of their ICU stay or discharge, whichever occurred first. RESULTS: 495 newborns who underwent venipunctures were included. The mean (SD) gestational age was 33.0 (4.4) weeks and duration of participation was 8.0 (4.5) days. A total of 257 (51.9%) neonates were very preterm (<33 weeks). The mean (SD; range) number of venipunctures per neonate during the study period was 3.8 (2.8; 1-19) for all neonates and 4.1 (2.9; 1-17) for neonates <33 weeks. Of the 1887 venipunctures, 1164 (61.7%) were performed successfully in one attempt, 437 (23.2%) with continuous analgesia, 1434 (76.0%) with specific preprocedural analgesia. In multivariate models, lack of preprocedural analgesia was associated with higher disease-severity score, intrauterine growth retardation, invasive or noninvasive ventilation, venipuncture performed on the first day of hospitalization or at nighttime, and the use of continuous sedation/analgesia. High pain scores were significantly associated with absence of parents during procedures, surgery during the study period, and higher number of attempts. CONCLUSIONS: Venipuncture is very frequent in preterm and term neonates in the ICUs. 76% were performed with preprocedural analgesia. Strategies to reduce the number of attempts and to promote parental presence seem necessary.