ABSTRACT
Introduction: Morquio syndrome or mucopolysaccharidosis type IV-A (MPS IV-A) is an autosomal recessive disease caused by biallelic variants in the GALNS gene, encoding the lysosomal enzyme GalN6S, responsible for glycosaminoglycan keratan sulfate and chondroitin-6-sulfate degradation. Studies have shown that the degree of evolutionary and chemical divergence of missense variants in GalN6S when compared to ancestral amino acids is associated with the severity of the syndrome, suggesting a genotype-phenotype correlation. There is little information on Latin American patients with MPS IV-A that replicate these findings. This study aimed to characterize the phenotype and genotype from patients with MPS IV-A, who are under Enzyme Replacement Therapy at the Children's Neuropsychiatry Service of the Hospital Clínico San Borja Arriarán, Santiago, Chile, and to determine if there is any association between genotype and phenotype with those findings. Methods: Information was collected from medical charts, all patients went through a GalN6S enzymatic activity measurement in leukocytes from peripheral blood, and the GALNS gene was sequenced for all cases. Results: 12 patients with MPS IV-A were recruited, all patients presented multisystem involvement, mostly skeletal, and 75% of cases underwent surgical interventions, and cervical arthrodesis was the most frequent procedure. In regards of the genotype, the two most frequent variants were c.319+2T>C (n = 10, 41.66%) and p.(Arg386Cys) (n = 8, 33.33%), the first one was previously described in 2018 in a patient from Chile [Bochernitsan et al., 2018]. Conclusion: This is the first time that a genotype-phenotype correlation has been studied by analyzing the variants effect on the molecular structure of human GalN6S and the evolutionary conservation degree of affected residues in a cohort of patients in Chile. Albeit our work could not find statistically significant associations, we may infer that the evolutionary conservations of affected amino acids and the effect of variants on enzyme structure may play a main role. Further analyzes should consider a meta-analysis of published cases with genotype data and larger samples and include other variables that could provide more information. Finally, our data strongly suggest that variant c.319+2T>C could have a founder effect in Chilean patients with MPS IV-A.
ABSTRACT
Resumen: Objetivos: Describir la prevalencia de trastornos respiratorios del sueño (TRS) en escolares chilenos y estudiar factores de riesgo asociados. Pacientes y Método: Estudio transversal y descriptivo. Se enviaron cuestionarios a los padres de niños de 1° año básico de colegios de la Región Metropolitana (Santiago), Región del Biobío (Concepción, Chillán, Yumbel) y Región de Magallanes (Porvenir y Puerto Natales). Se consignaron datos antropométricos, desempeño escolar, características del hogar, contaminantes intradomiciliarios, antecedentes médicos y síntomas actuales de asma, rinitis alérgica y dermatitis atópica. Se determinó estado nutricional según zIMC. Se aplicó un cuestionario de sue ño pediátrico validado en español (pediatric sleep questionnaire, PSQ). Resultados: 564 encuestas fueron analizadas, la edad mediana fue 6 años (rango 5 a 9), 44,9% sexo masculino. La prevalencia de TRS fue 17,7% (n = 100): 6% en Vitacura (Metropolitana), 28,7% en Chillán (Biobío) y 36,4% en Puerto Natales (Magallanes) (p = 0,001). El grupo con TRS tuvo mayor proporción de hombres (54,5 vs 42,8%, p = 0,033), menor rendimiento académico (promedio general 6,36 ± 0,48 vs 6,56 ± 0,34, p = 0,001), menor educación superior materna (44,4 vs 69,9%, p = 0,001) y mayor exposición a contaminantes intradomiciliarios que aquellos sin TRS. Posterior al análisis multivariado se mantu vieron como predictor de TRS el haber presentado síntomas de rinitis en últimos 12 meses (OR 4,79; IC 95% 2,20-10,43) y el nivel educacional básico o medio de la madre (OR 3,51; IC 95% 1,53-8,02). Conclusiones: Los escolares chilenos presentan una alta prevalencia de TRS, con diferencias demo gráficas. Se asoció a factores de riesgo social, a factores más específicos de daño pulmonar y a peor cantidad y calidad del sueño.
Abstract: Objectives: To describe the prevalence of sleep-disordered breathing (SDB) in Chilean schoolchil dren and study associated risk factors. Patients and Method: We carried out a transversal and des criptive study. Questionnaires were sent to the parents of children attending first year of elementary school in the Metropolitan Region (Santiago), the Biobío Region (Concepción, Chillán, Yumbel) and the Magallanes Region (Porvenir and Puerto Natales). Anthropometric data, school performan ce, household characteristics, indoor pollutants, medical history, and current symptoms of asthma, allergic rhinitis, and atopic dermatitis were recorded. The nutritional status was determined accor ding to z-BMI. A pediatric sleep questionnaire validated in Spanish (PSQ) was applied. Results: 564 questionnaires were analyzed, the median age was six years (range 5 to 9), 44.9% male. The SDB prevalence was 17.7% (n = 100): 6% in Vitacura (Metropolitan Region), 28.7% in Chillán (Biobío Region), and 36.4% in Puerto Natales (Magallanes Region) (p = 0.001). The group with SDB had a higher proportion of men (54.5 vs 42.8%, p = 0.033), lower academic performance (overall grade point average 6.36 ± 0.48 vs 6.56 ± 0.34, p = 0.001), lower maternal higher education (44.4% vs 69.9%, p = 0.001), and higher exposure to indoor pollutants than those without SDB. After the multivariate analysis, symptoms of rhinitis in the last 12 months (OR 4.79, 95% CI 2.20-10.43) and lower maternal educational level (OR 3.51; 95% CI 1.53-8.02) remained as predictors of SDB. Con clusions: Chilean schoolchildren have a high prevalence of SDB with demographic differences. It was associated with social risk factors, more specific factors of lung damage, and worse sleep quality and quantity.
Subject(s)
Humans , Male , Female , Child, Preschool , Child , Sleep Apnea Syndromes/epidemiology , Sleep Apnea Syndromes/etiology , Chile/epidemiology , Prevalence , Cross-Sectional Studies , Risk FactorsABSTRACT
OBJECTIVES: To describe the prevalence of sleep-disordered breathing (SDB) in Chilean schoolchil dren and study associated risk factors. PATIENTS AND METHOD: We carried out a transversal and des criptive study. Questionnaires were sent to the parents of children attending first year of elementary school in the Metropolitan Region (Santiago), the Biobío Region (Concepción, Chillán, Yumbel) and the Magallanes Region (Porvenir and Puerto Natales). Anthropometric data, school performan ce, household characteristics, indoor pollutants, medical history, and current symptoms of asthma, allergic rhinitis, and atopic dermatitis were recorded. The nutritional status was determined accor ding to z-BMI. A pediatric sleep questionnaire validated in Spanish (PSQ) was applied. RESULTS: 564 questionnaires were analyzed, the median age was six years (range 5 to 9), 44.9% male. The SDB prevalence was 17.7% (n = 100): 6% in Vitacura (Metropolitan Region), 28.7% in Chillán (Biobío Region), and 36.4% in Puerto Natales (Magallanes Region) (p = 0.001). The group with SDB had a higher proportion of men (54.5 vs 42.8%, p = 0.033), lower academic performance (overall grade point average 6.36 ± 0.48 vs 6.56 ± 0.34, p = 0.001), lower maternal higher education (44.4% vs 69.9%, p = 0.001), and higher exposure to indoor pollutants than those without SDB. After the multivariate analysis, symptoms of rhinitis in the last 12 months (OR 4.79, 95% CI 2.20-10.43) and lower maternal educational level (OR 3.51; 95% CI 1.53-8.02) remained as predictors of SDB. Con clusions: Chilean schoolchildren have a high prevalence of SDB with demographic differences. It was associated with social risk factors, more specific factors of lung damage, and worse sleep quality and quantity.
