Newborn Screening Program for Cystic Fibrosis in Cuba: Three Years' Experience

ABSTRACT In Cuba, newborn screening (NBS) for cystic fibrosis (CF) was introduced in January 2019. The results from the first three years of the CF NBS program are presented. An IRT/IRT protocol was followed using a cut-off value of 50 ng/mL. In this period 281,717 neonates were screened, 2,197 samples had increased IRT values, and a second sample was necessary (recall rate=0.78%). In 686 (0.24%) neonates, IRT was still elevated, and they were referred for clinical evaluation. Twenty-one children were confirmed by sweat test and molecular biology. Eighteen newborns presented variant F508del. A false negative case was reported. Demographic data of 32,764 neonates were collected. The average age of sampling was six days with results available at 11 days of life, but 1.7% of the samples were collected 20 days after birth. The mean IRT value was 12.7±11.7 ng/mL (ranging 0-283 ng/mL) with a calculated 98.5 percentile value of 42.4 ng/mL. On average, the samples were processed five days after collection and two days after they were received at the laboratory. Although CF NBS program in Cuba is just beginning, it can be predicted that CF will be one of the most frequent inherited-metabolic diseases in the Cuban population.

Pilot study for cystic fibrosis neonatal screening: the Cuban experience.

Background In Cuba, no screening program for cystic fibrosis (CF) has been implemented yet. The ultramicro enzyme-linked immunosorbent assay (UMELISA)® TIR NEONATAL has been developed for the measurement of immunoreactive trypsin (IRT) in dried blood spots on filter paper. The analytical performance of the kit was evaluated in the national network of laboratories. Methods Newborn dried blood samples (DBS) were evaluated in 16 laboratories. An IRT/IRT/DNA protocol was followed using a cut-off value of 50 ng/mL. The mean, median and percentiles of the distribution were calculated and a two-sample t-test with unequal variance was used for statistical analysis. Influence of perinatal factors on IRT levels was analyzed. Results From January to June 2018, 6470 newborns were studied, obtaining a mean IRT value of 12.09 ng/mL (ranging 0-358 ng/mL) and a median of 8.99 ng/mL. Fifty-two samples (0.78%) were above the cut-off level and 16 samples (0.24%) were elevated in the re-screening process. One of them was confirmed positive by molecular biology (phe508del/c.3120 + 1G > A), constituting the first newborn screened and diagnosed early in Cuba. Second DBS samples were collected on average at 14 days and processed in the laboratory at 16 days of birth. Significant differences were observed (p < 0.05) when evaluating the influence of gender, birth weight (BW) and gestational age (GA) on the IRT values. Lower IRT concentrations were found in samples processed after 10 days of collection. Conclusions The performance of UMELISA® TIR NEONATAL in the laboratories has been satisfactory; hence CF newborn screening (NBS) was extended throughout the country from January 2019.

Antenatal testing for cystic fibrosis in Cuba, 1988-2011.

INTRODUCTION Cystic fibrosis is a multisystem autosomal recessive disease with wide variability in clinical severity. It is incurable and characterized by elevated and premature mortality, as well as poor quality of life. Its frequency, lethality and devastating impact on both the physical and psychological wellbeing of patients and their families, make it a serious health problem. Its frequency in Cuba is 1 in 9862 live births, where marked molecular heterogeneity of the CFTR gene makes molecular diagnosis difficult. Six mutations have been identified that together enable molecular characterization of only 55.5% of cystic fibrosis chromosomes. This paper presents national results of antenatal diagnostic testing, using direct and indirect methods, for detection of cystic fibrosis. OBJECTIVE Characterize the Cuban public health system's experience with antenatal molecular testing for cystic fibrosis from 1988 through 2011. METHODS A retrospective descriptive study was conducted with results of antenatal diagnostic testing of amniotic fluid, performed nationwide from 1988 through 2011, for 108 fetuses of couples with some risk of having children affected by cystic fibrosis, who requested testing. Polymerase chain reaction detected mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A, and markers XV2C and KM19. Data were analyzed using absolute frequencies and percentages, and presented in tables. RESULTS For 93 cases (86.1%), testing for cystic fibrosis was done using direct analysis of mutations p.F508del, p.G542X, p.R1162X, p.R334W, p.R553X and c.3120+1G>A; five cases (4.6%) were tested indirectly using markers XV2C/Taq I and KM19/Pst I; and 10 (9.3%) were tested using a combination of the two methods. A total of 72 diagnoses (66.7% of studies done) were concluded, of which there were 20 healthy fetuses, 16 affected, 27 carrier, and 9 who were either healthy or carriers of an unknown mutation. CONCLUSIONS Direct or indirect molecular study was successfully used in over half of antenatal tests requested by couples throughout Cuba at risk of having children affected by cystic fibrosis, which is of great social value because of CF's burden on affected persons and their families.

Manejo de la patología quirúrgica de la glándula parótida: revisión de 54 casos / Management of the surgical pathology of the parotid gland: A review of 54 cases

Introducción y objetivos: El abordaje de la patología quirúrgica de la glándula parótida y los resultados obtenidos son relativamente uniformes. Sin embargo, tanto en la vertiente diagnóstica como en la terapéutica, existen algunos aspectos controvertidos cuya discusión planteamos a partir de la experiencia reciente de nuestro servicio. Métodos: Se realizó un estudio descriptivo retrospectivo sobre pacientes sometidos a parotidectomía por cualquier indicación entre julio de 2004 y junio de 2009 (5 años). Resultados: Se realizaron 54 parotidectomías en 52 pacientes. La TC fue el estudio de imagen preoperatorio más utilizado. La validez de la PAAF fue del 93,3%. El 76% fueron procesos benignos; entre ellos el 7,3% de causa inflamatoria. Todas las intervenciones se realizaron con monitorización electrofisiológica del nervio facial a partir de abril de 2005. Se realizó parotidectomía superficial en el 75,6% de los procesos benignos. La incidencia de paresias faciales transitorias en patología benigna fue del 14,6% (todas grados II y III). Dos casos (ambos con parotidectomía total) tuvieron secuelas permanentes de movilidad facial. La incisión de ritidectomía se utilizó preferentemente en mujeres jóvenes. Conclusiones: Identificamos como puntos de controversia, bien por discrepancia con la evidencia científica o por evidencia insuficiente: el papel diagnóstico de la RM, la validez y utilidad de la PAAF, las indicaciones del tratamiento quirúrgico, la necesidad de monitorización del nervio facial, y la consideración de los aspectos cosméticos, en particular las indicaciones de la incisión de ritidectomía (AU)

Introduction and aim of the study: The management of the surgical pathology of the parotid gland and its results are relatively uniform. However, both in the diagnostic and the therapeutic aspects, there are some controversial issues which we discuss from the point of view of recent experience at our department. Methods: A descriptive and retrospective study was conducted on patients who underwent parotidectomy for any indication between July 2004 and June 2009 (5 years). Results: Fifty four parotidectomies were performed in 52 patients. CT was the most commonly used preoperative diagnostic imaging study. The accuracy of FNAB was 93.3%. 76% were benign processes; among them 7.3% with inflammatory causes. All of the surgical procedures from April 2005 onwards were performed with electrophysiological monitoring of the facial nerve. Superficial parotidectomy was performed in 75.6% of benign cases. The incidence of transient facial paresis in benign pathologies was of 14.6% (all of them of grades II and III). Two cases (both with total parotidectomy) had permanent facial mobility sequelae. The rhytidectomy incision was used preferentially in young women. Conclusions: The controversial issues identified, due either to discrepancies or lack of enough evidence, were: the diagnostic role of MRI, the validity and usefulness of FNAB, the indications of surgical treatment, the need for facial nerve monitoring and the consideration of cosmetic aspects, in particular the indications of rhytidectomy incision (AU)

[Management of the surgical pathology of the parotid gland: A review of 54 cases]. / Manejo de la patología quirúrgica de la glándula parótida: revisión de 54 casos.

INTRODUCTION AND AIM OF THE STUDY: The management of the surgical pathology of the parotid gland and its results are relatively uniform. However, both in the diagnostic and the therapeutic aspects, there are some controversial issues which we discuss from the point of view of recent experience at our department. METHODS: A descriptive and retrospective study was conducted on patients who underwent parotidectomy for any indication between July 2004 and June 2009 (5 years). RESULTS: Fifty four parotidectomies were performed in 52 patients. CT was the most commonly used preoperative diagnostic imaging study. The accuracy of FNAB was 93.3%. 76% were benign processes; among them 7.3% with inflammatory causes. All of the surgical procedures from April 2005 onwards were performed with electrophysiological monitoring of the facial nerve. Superficial parotidectomy was performed in 75.6% of benign cases. The incidence of transient facial paresis in benign pathologies was of 14.6% (all of them of grades II and III). Two cases (both with total parotidectomy) had permanent facial mobility sequelae. The rhytidectomy incision was used preferentially in young women. CONCLUSIONS: The controversial issues identified, due either to discrepancies or lack of enough evidence, were: the diagnostic role of MRI, the validity and usefulness of FNAB, the indications of surgical treatment, the need for facial nerve monitoring and the consideration of cosmetic aspects, in particular the indications of rhytidectomy incision.

Common mutations in Cuban cystic fibrosis patients.

So far, more than 1500 mutations have been reported in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. Mutational spectrum varies in accordance with geographic and/or ethnic origin. In this study, we have analyzed seven common CF mutations (p.F508del, p.G542X, p.R1162X, p.N1303K, p.R334W, p.R553X and c.3120+1G>A) taking into account the ethnic origin of the Cuban population which is mainly influenced by Spanish and sub-Sahara African contribution. All but p.N1303K have been detected in our patients, the p.F508del being the most prevalent (37.9%). Overall, six mutations showed frequencies above 1% accounting for 55.5% of the Cuban CF alleles.

Epidemiology of prenatal genetic and environmental factors of mental retardation in cuba.

Introduction: One of the most sensitive disabilities in human beings is intellectual disability. In April, 2003, a 10-month study was completed of all persons in Cuba with mental retardation (MR), producing results that included epidemiological variables on a national scale. Objective: Through follow-up research, this paper describes and analyzes 4 prenatal factors associated with MR: Down syndrome (DS), fragile X syndrome (FXS), consanguinity, and maternal alcohol use during pregnancy, in order to provide recommendations for health system decision-makers on consolidating prevention strategies at the community level and improving individual attention to persons with MR. Materials & Methods: All studies were carried out on the basis of strict ethical principles. Data for the 4 prenatal factors was gleaned from the national study's database. Additional data on affected individuals was obtained through home visits. A previously developed screening instrument was used for clinical genetic analysis to classify possible MR causal factors as prenatal, perinatal, postnatal, psychosis, and unclassifiable. Prenatal included causal factors such as: genetic (by clinical genetic examination, metabolic screening in urine, and routine karyotypes); nonspecific (evidence of prenatal causal factor without diagnosis of genetic or environmental etiology); and environmental (prenatal medical history of biological, physical, or chemical teratogens, endocrine-metabolic diseases, or other maternal diseases known to affect fetal neurodevelopment). Frequency, prevalence, and percentages were reported using a descriptive statistical method. Impact of interventions and actions over time were also compared. Results: MR prevalence in Cuba is 1.25%, lower than the value of 2%-3% reported in developed countries. National prevalence of DS was found to be 4.3 per 10,000 population, representing 22.1% of persons with MR attributed to an ascertained genetic cause. FXS prevalence in a population of individuals of both sexes with MR, initially classified as nonspecific prenatal, psychosis, and unclassifiable, was 2.5 per 1,000 of that population; however, in males of the same population, prevalence was 3.7 per 1,000. At this first stage, such results indicate that this syndrome contributes biologically to the 1.46:1 male/female ratio among the 140,489 individuals with MR. Maternal alcohol use during pregnancy was found in 4.22% of persons with MR and consanguinity was present in 6.89% of the population with MR (10.9% of persons with mild prenatal MR and 14.2% with severe MR). This national data is subdivided by regions and provinces in this paper. Conclusions: Prevalence of MR in Cuba is lower than reference values for developed countries. Knowledge generated by this study about 4 specific causes of MR constitutes pioneering research in the Cuban context, contributing to the field of medical genetics. The results offer the basis for formulation of new scientific contributions related to MR genetics as well as preventive approaches to such genetic factors as consanguinity and to environmental factors such as maternal alcohol use during pregnancy, which affect or target embryo-fetal development of the nervous system.