Avances y logros del programa de tamiz metabólico neonatal (2012-2018)

Flores, Erika Paola García; Maldonado, Nazarea Herrera; Trejo, Mirna Angélica Hinojosa; Vázquez, Mónica Vergara; Castillo, María Elizabeth Halley

doi:10.18233/apm39no6pp57s-65s1722

Cited by 19 publications

(28 citation statements)

References 1 publication

(1 reference statement)

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“…The number of patients detected by NBS in our center increased from 54.1% in 2015 [6] to 78.2%. This significant increment (p = 0.001) could be related to the optimization of the NBS system in Mexico, although it still does not reach the optimal goal of having a total NBS coverage for this disease [21]. This finding agrees with the fact that improvements in the NBS programs increase the detection of MHP forms [22,23].…”

Section: Discussionmentioning

confidence: 54%

An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations

Vela-Amieva

Alcántara-Ortigoza

Ibarra-González

et al. 2021

Genes

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Establishing the genotypes of patients with hyperphenylalaninemia (HPA)/phenylketonuria (PKU, MIM#261600) has been considered a cornerstone for rational medical management. However, knowledge of the phenylalanine hydroxylase gene (PAH) mutational spectrum in Latin American populations is still limited. Herein, we aim to update the mutational PAH spectrum in the largest cohort of HPA/PKU Mexican patients (N = 124) reported to date. The biallelic PAH genotype was investigated by Sanger automated sequencing, and genotypes were correlated with documented biochemical phenotypes and theoretical tetrahydrobiopterin (BH4) responsiveness. Patients were biochemically classified as having classic PKU (50%, 62/124), mild PKU (20.2%, 25/124) and mild HPA (29.8%, 37/124). Furthermore, 78.2% of the included patients (97/124) were identified by newborn screening. A total of 60 different pathogenic variants were identified, including three novel ones (c. 23del, c. 625_626insC and c. 1315 + 5_1315 + 6insGTGTAACAG), the main categories being missense changes (58%, 35/60) and those affecting the catalytic domain (56.6%, 34/60), and c. 60 + 5G > T was the most frequent variant (14.5%, 36/248) mainly restricted (69.2%) to patients from the central and western parts of Mexico. These 60 types of variants constituted 100 different biallelic PAH genotypes, with the predominance of compound-heterozygous ones (96/124, 77%). The expected BH4 responsiveness based on the PAH genotype was estimated in 52% of patients (65/124), mainly due to the p. (Val388Met) (rs62516101) allele. Instead, our study identified 27 null variants with an allelic phenotype value of zero, with a predominance of c. 60 + 5G > T, which predicts the absence of BH4 responsiveness. An identical genotype reported in BIOPKUdb was found in 92/124 (74%) of our patients, leading to a genotype–phenotype concordance in 80/92 (86.9%) of them. The high number of variants found confirms the heterogeneous and complex mutational landscape of HPA/PKU in Mexico.

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Section: Discussionmentioning

confidence: 54%

An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations

Vela-Amieva

Alcántara-Ortigoza

Ibarra-González

et al. 2021

Genes

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“…For many years , the mandatory NBS program in Mexico only included the detection of congenital hypothyroidism (CH). The coverage of public NBS programs for CH has made significant progress [27], and in 2015, the panel was extended to include PKU, congenital adrenal hyperplasia, galactosemia, and recently, G6PDd and cystic fibrosis [28]. However, the inclusion of other genetic disorders appears remote [29].…”

Section: Discussionmentioning

confidence: 99%

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Ibarra-González

Fernández-Lainez

Guillén-López

et al. 2021

J. inborn errors metab. screen.

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Introduction: Any abnormal newborn screening (NBS) test should be subjected to appropriate diagnostic tests and should be followed. Once the newborn has been diagnosed and treated, the family should receive comprehensive genetic services. Aim: To present the experience of studying older siblings of patients with inborn errors of metabolism (IEM) identified by NBS in a single-national follow-up reference center. Methods: A retrospective analysis of medical files of the IEM patients detected by NBS was conducted. All those older siblings who tested positive for the same IEM of the patient detected by newborn screening were included. Results: A total of 26 positive siblings from 18 families with seven different IEM were found (phenylketonuria, argininemia, glucose-6-phosphate dehydrogenase deficiency, 3-methylcrotonyl-CoA carboxylase deficiency, dihydropteridine reductase deficiency, tyrosinemia type 3, and medium chain acyl-CoA dehydrogenase deficiency). The age range of the affected siblings was 2 to 19 years old, with a mean age of 8.5 years. Ten older siblings (38.5%) had clinical consequences for the disease, including severe intellectual disability. Conclusions: It is necessary to study older siblings, and family history and genetic counseling of all NBS-detected families should be recommended, especially in countries where expanded NBS programs are beginning.

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“…However, when grouped, estimations show an incidence of 1:500-1:1500 in live newborns, and from these, approximately 50% develop the disorder in the neonatal period in Mexico 7 . Today, advances in new technology have optimized the sensitivity and specificity of laboratory tests, reducing false negatives almost completely and endorsing the quality of the results 8 . The term cutoff point (CP) or biological reference interval (BRI) is an internationally accepted and utilized concept applied to establish and use relevant data for interpreting medical observations.…”

Section: Introductionmentioning

confidence: 99%

Determination and comparison of neonatal screening biomarker cutoff points in Mexican newborns against the manufacturerÓ?s cutoff point

Cobos-Puc¹,

Martínez-Tapia²,

Martínez-Castillo³

et al. 2023

RMU

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Objective:The objective of the study was to determine the cutoff points (CP) of nine neonatal screening biomarkers performed at the Laboratory of the Center for Neonatal and Genetic Studies in Mexico City, comparing them with the CP recommended by the manufacturer of the reagents. Materials and methods: A descriptive cross-sectional research was carried out. The study included 2805 newborns aged 1-30 days, who had a drop of dried whole blood collected on filter paper, then quantified for their concentrations of thyroid-stimulating hormone, thyroxine, phenylalanine, immunotrypsin, galactose-1-phosphate uridyltransferase, galactose, glucose-6-phosphate dehydrogenase, biotinidase, and 17-alpha hydroxyprogesterone, by immunofluorescence method (DELFIA, PerkinElmer LifeSciences time-resolved fluorometry). The cutoff point (excluding atypical values) was calculated with the data obtained for each test, and the mean and standard deviation were determined. Sensitivity and specificity were determined with receiver operating characteristic (ROC) curves. The determined CPs were compared with the CPs recommended by the manufacturer of the reagents. Results: Except for T4, it was shown that, when comparing the CP obtained, these were lower compared to the CPs recommended by the manufacturer. Conclusion: The CPs obtained in Mexican neonates differ from those recommended by the manufacturer. In addition, CPs are analytically acceptable, as they have high sensitivity and specificity. Consequently, these CPs can be used as a reference in clinical practice for the possible early detection of metabolic diseases in newborns.

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Avances y logros del programa de tamiz metabólico neonatal (2012-2018)

Cited by 19 publications

References 1 publication

An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations

An Updated PAH Mutational Spectrum of Phenylketonuria in Mexican Patients Attending a Single Center: Biochemical, Clinical-Genotyping Correlations

Importance of Studying Older Siblings of Patients Identified by Newborn Screening: a Single-Center Experience in Mexico

Determination and comparison of neonatal screening biomarker cutoff points in Mexican newborns against the manufacturerÓ?s cutoff point

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