Frequency of rs1051338 and rs116928232 Variants in Individuals from Northwest Mexico.

BACKGROUND: LIPA, situated on chromosome 10q23.2-q23.3, encodes the enzyme lysosomal acid lipase (LAL) (EC 3.1.1.13). Genetic alterations in LIPA lead to lysosomal acid lipase deficiency (LALD), an inborn error causing lipid metabolism anomalies and impairing cholesterol and triacylglyceride degradation. Over 40 LIPA variants have been documented, yet this study focuses on just two. The rs1051338 variant (NM_000235:c.46A>C) affects the signal peptide in Exon 2, whereas rs116928232, located in Exon 8, alters the splice site (NM_000235:c.894G>A), impacting lysosomal acid lipase activity. Considering the diverse clinical manifestations of LALD and the rising hepatic steatosis prevalence in Mexican population, mainly due to diet, these variants were investigated within this demographic to uncover potential contributing factors. This study aimed to reveal the frequency of rs1051338 and rs116928232 among healthy mestizo individuals in Northwest Mexico, marking a significant genetic exploration in this demographic. METHODS: Three hundred ten healthy mestizo individuals underwent PCR-RFLP analysis for both variants, and Sanger sequencing was performed for variant rs116928232. Bioinformatic analysis was also performed to predict protein changes. RESULTS: Allele frequencies for rs1051338 (FA = 0.39, p value = 0.15) and rs116928232 (FA = 0.0016, p value = 0.49) aligned with reported data, while bioinformatic analysis allowed us to identify the protein alteration observed in both variants; finally, the variants showed no linkage between them (normalized D' = 1.03, p value = 0.56). CONCLUSIONS: Allelic frequencies closely matched reported data, and protein structure analysis confirmed variant impacts on LAL enzyme function. Notably, this study marks the first analysis of rs1051338 and rs116928232 in a healthy Mexican mestizo population.

Causas del hidrops fetal: experiencia en un hospital obstétrico del Occidente de México / Etiology of fetal hydrops: experience in an obstetric hospital in western Mexico

Resumen OBJETIVO: Identificar las causas de hidrops fetal no inmunitario en un hospital obstétrico de referencia del Occidente de México. MATERIALES Y MÉTODOS: Estudio de serie de casos, con un muestreo no probabilístico por conveniencia, llevado a cabo de octubre de 2014 a septiembre de 2015 al que se incluyeron pacientes (entre las 15 y 38 semanas de embarazo), mayores de edad (en casos de menores de edad se solicitó consentimiento informado a los padres o tutores), con diagnóstico de hidrops fetal por ultrasonido obstétrico. Para el análisis estadístico se generó una base de datos en Excel y se aplicó estadística descriptiva. RESULTADOS: Se reunieron 33 embarazadas en quienes el hidrops fetal no inmunitario fue el más frecuente (n = 31) y la causa idiopática más común (n = 10) seguida por errores innatos del metabolismo, alteraciones cromosómicas y cardiacas (n = 6 de cada una). Posteriormente, las causas hematológicas (n = 4), linfáticas y sindrómicas (n = 3 de cada una), y las infecciosas y tumorales (n = 1 de cada una). En este estudio los errores innatos del metabolismo (específicamente síndrome Sly) tuvieron una frecuencia superior a la referida en la bibliografía. CONCLUSIONES: Los errores innatos del metabolismo, las anomalías cromosómicas y cardiacas fueron la segunda causa más frecuente de hidrops fetal no inmunitario. Se sugiere tener en cuenta las causas metabólicas en el enfoque diagnóstico del hidrops fetal, sobre todo para el establecimiento del tratamiento temprano.

Abstract OBJECTIVE: To identify the causes of nonimmune fetal hydrops fetalis in an obstetric referral hospital in Western Mexico. MATERIALS AND METHODS: Case series study, with non-probabilistic sampling by convenience, carried out from October 2014 to September 2015 which included patients (between 15 and 38 weeks of pregnancy), of legal age (in cases of minors, informed consent was requested from parents or guardians), with a diagnosis of fetal hydrops fetalis by obstetric ultrasound. For statistical analysis, an Excel database was generated and descriptive statistics were applied. RESULTS: Thirty-three pregnant women were included, in whom non-immune fetal hydrops fetalis was the most frequent (94%) and idiopathic was the most common cause (n = 10), followed by inborn errors of metabolism, chromosomal and cardiac alterations (n = 6 each). This was followed by hematologic (n = 4), lymphatic and syndromic causes (n = 3 each), and infectious and tumor causes (n = 1 each). In this study, inborn errors of metabolism (specifically Sly syndrome) had a higher frequency than that reported in the literature. CONCLUSIONS: Inborn errors of metabolism, chromosomal and cardiac abnormalities were the second most frequent cause of nonimmune fetal hydrops. It is suggested that metabolic causes be taken into account in the diagnostic approach to fetal hydrops, especially for the establishment of early treatment.

Biochemical diagnosis of mucopolysaccharidosis in a Mexican reference center.

Mucopolysaccharidoses (MPS) are a group of genetic disorders, each resulting from the deficiency of one of the lysosomal enzymes that catabolizes mucopolysaccharides. For the accurate diagnosis of the disease, the quantification of a specific enzymatic activity is needed. In the present study, we analyzed seven MPS over several periods of time ranging from 2 to 5 years in a reference center in Mexico. During this time, a total of 761 samples belonging to 505 individuals with suspected MPS were analyzed. A total of 198 (26.01%) positive results were found. Among these, MPS IVA accounted for the highest frequency of positive results (49.10%), followed by MPS III (17.69%, IIIA: 11.80% and IIIB: 5.89%). Adjusting for the number of births per year, the estimated incidence per 100,000 births for MPS analyzed were as follows: MPS I: 0.19, MPS II: 0.15, MPS IIIA: 0.26, MPS IIIB: 0.13, MPS IVA: 1.10, MPS VI: 0.17 and MPS VII: 0.23, and the combined estimated incidence of MPS was 2.23 per 100,000 births; however, this incidence seems to be highly underestimated when compared with the results of newborn screenings.