RESUMO
BACKGROUND: Wieacker-Wolff syndrome is an ultra-rare disease with X-linked inheritance characterized by arthrogryposis, intellectual disability, microcephaly, and distal limb muscle atrophy. Ophthalmic abnormalities such as ptosis, strabismus, and oculomotor apraxia have been reported in half of the patients. Wieacker-Wolff syndrome female-restricted (WRWFFR) is an even rarer disease recently used for females with a more severe phenotype. MATERIALS AND METHODS: Clinical geneticist and ophthalmic examination, neuroimaging, and exome sequencing. RESULTS: A 4 years-old girl with developmental and language delay, microcephaly, camptodactyly, digital pads, and arthrogryposis was identified by the clinical geneticist. Ophthalmic examination revealed deep-set eyes, high hyperopic astigmatism in both eyes, and reduced retinal nerve fiber layer thickness measured by optical coherence tomography. Exome sequencing identified a novel, probably pathogenic variant in the ZC4H2 gene NM_018684.3:c.145A>T p. (Lys49*) in heterozygosis. DISCUSSION: WRWFFR is an ultra-rare disease with X-linked inheritance by variants in the ZC4H2 gene. This case reports a girl with a novel nonsense variant in the ZC4H2 gene and a severe phenotype; previous reports have identified WRWFFR in females with large deletions and nonsense mutations which could explain the manifestations in the current case report. A complete ophthalmic examination should be considered in patients with WRWFFR to detect the possibly associated optic nerve involvement and other previously described manifestations such as ptosis and strabismus.
Assuntos
Artrogripose , Deficiência Intelectual , Microcefalia , Estrabismo , Humanos , Feminino , Pré-Escolar , Artrogripose/genética , Microcefalia/genética , Doenças Raras , Deficiência Intelectual/genética , Nervo Óptico , Proteínas Nucleares , Peptídeos e Proteínas de Sinalização IntracelularRESUMO
(1) Background: The interaction between single nucleotide variants (SNVs) associated with congenital heart diseases (CHDs) and their gene methylation status has not been well researched. The aim of the present study was to determine if there is a relationship between the methy lation status (MS) of genes and the allelic variants associated with CHDs. (2) Methods: Seven SNVs of the genes AXIN1, TBX1, TBX20, and MTHFR were selected from the literature. DNA extraction, genotyping, and a methylation analysis were performed on healthy subjects and subjects with CHDs. (3) Results: Twenty-two subjects with CHDs were selected as the case group (15 with ventricular septal defects (VSDs) and 7 with atrial septal defects (ASDs)), and 44 healthy subjects comprised the control group. The MTHFR and AXIN1 genes were hypermethylated in the control group when compared to the case group. When analyzed separately, those with atrial septum defects exhibited greater methylation, except for the gene MTHFR where there were no differences. Only the alternate alleles of MTHFR showed a significantly different methylation status in those without cardiopathy. (4) Conclusions: The MTHFR and AXIN genes were hypermethylated in the control group; however, only the alternate alleles of MTHFR (rs1801133 and rs1801131) showed a significantly different methylation status.
Assuntos
Cardiopatias Congênitas , Humanos , Estudos de Casos e Controles , Cardiopatias Congênitas/genética , Alelos , Fatores de Risco , Metilação de DNARESUMO
BACKGROUND: DNA methylation is the best epigenetic mechanism for explaining the interactions between nutrients and genes involved in intrauterine growth and development programming. A possible contributor of methylation abnormalities to congenital heart disease is the folate methylation regulatory pathway; however, the mechanisms and methylation patterns of VSD-associated genes are not fully understood. OBJECTIVE: To determine if maternal dietary intake of folic acid (FA) is related to the methylation status (MS) of VSD-associated genes (AXIN1, MTHFR, TBX1, and TBX20). METHODS: Prospective case-control study; 48 mothers and their children were evaluated. The mothers' dietary variables were collected through a food frequency questionnaire focusing on FA and the consumption of supplements with FA. The MS of promoters of genes was determined in the children. RESULTS: The intake of FA supplements was significantly higher in the control mothers. In terms of maternal folic acid consumption, significant differences were found in the first trimester of pregnancy. Significant differences were observed in the MS of MTHFR and AXIN1 genes in VSD and control children. A correlation between maternal FA supplementation and MS of AXIN1 and TBX20 genes was found in control and VSD children, respectively. CONCLUSIONS: A lower MS of AXIN1 genes and a higher MS of TBX20 genes is associated with FA maternal supplementation.
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Ácido Fólico/metabolismo , Estudos de Associação Genética , Predisposição Genética para Doença/genética , Comunicação Interventricular/genética , Estudos de Casos e Controles , Criança , Metilação de DNA , Dieta , Suplementos Nutricionais , Epigênese Genética , Feminino , Cardiopatias Congênitas , Homocistinúria , Humanos , Masculino , Metilenotetra-Hidrofolato Redutase (NADPH2)/deficiência , Espasticidade Muscular , Gravidez , Estudos Prospectivos , Transtornos PsicóticosRESUMO
Menkes disease (MD) is a rare and often lethal X-linked recessive syndrome, characterized by generalized alterations in copper transport and metabolism, linked to mutations in the ATPase copper transporting α (ATP7A) gene. Our objective was to identify genomic alterations and circulating proteomic profiles related to MD assessing their potential roles in the clinical features of the disease. We describe the case of a male patient of 8 months of age with silvery hair, tan skin color, hypotonia, alterations in neurodevelopment, presence of seizures, and low values of plasma ceruloplasmin. Trio-whole-exome sequencing (Trio-WES) analysis, plasma proteome screening, and blood cell migration assays were carried out. Trio-WES revealed a hemizygous change c.4190C > T (p.S1397F) in exon 22 of the ATP7A gene. Compared with his parents and with child controls, 11 plasma proteins were upregulated and 59 downregulated in the patient. According to their biological processes, 42 (71.2%) of downregulated proteins had a participation in cellular transport. The immune system process was represented by 35 (59.3%) downregulated proteins (p = 9.44 × 10-11). Additional studies are necessary to validate these findings as hallmarks of MD.
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Movimento Celular/genética , Fenômenos do Sistema Imunitário/genética , Síndrome dos Cabelos Torcidos/genética , Proteoma/genética , Adolescente , Adulto , ATPases Transportadoras de Cobre/genética , Regulação para Baixo/genética , Feminino , Humanos , Lactente , Masculino , Mutação/genética , Proteômica/métodos , Regulação para Cima/genética , Sequenciamento do Exoma/métodos , Adulto JovemRESUMO
Aedes aegypti L. is the most important vector of arboviruses such as dengue, Zika, chikungunya, Mayaro, and yellow fever, which impact millions of people's health per year. MicroRNA profile has been described in some mosquito species as being important for biological processes such as digestion of blood, oviposition, sexual differentiation, insecticide resistance, and pathogens dissemination. We identified the miRNAs of Ae. aegypti females, males and eggs of a reference insecticide susceptible strain New Orleans and compared them with those other insects to determine miRNA fingerprint by new-generation sequencing. The sequences were analyzed using data mining tools and categorization, followed by differential expression analysis and conservation with other insects. A total of 55 conserved miRNAs were identified, of which 34 were of holometabolous insects and 21 shared with hemimetabolous insects. Of these miRNAs, 32 had differential expression within the stages analyzed. Three predominant functions of miRNA were related to embryonic development regulation, metamorphosis, and basal functions. The findings of this research describe new information on Ae. aegypti physiology which could be useful for the development of new control strategies, particularly in mosquito development and metamorphosis processes.
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Aedes/classificação , Aedes/genética , Insetos/classificação , Insetos/genética , MicroRNAs/genética , Animais , Evolução Molecular , Feminino , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , MasculinoRESUMO
B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is a hematological malignancy of immature B-cell precursors, affecting children more often than adults. The etiology of BCP-ALL is still unknown, but environmental factors, sex, race or ethnicity, and genomic alterations influence the development of the disease. Tools based on protein detection, such as flow cytometry, mass spectrometry, mass cytometry and reverse phase protein array, represent an opportunity to investigate BCP-ALL pathogenesis and to identify new biomarkers of disease. This review aims to document the recent advancements with respect to applications of proteomic technologies to study mechanisms of leukemogenesis, how this information could be used in the discovery of biological targets, and finally we describe the challenges of application of proteomic tools for the approach of BCP-ALL.
Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Proteômica/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/patologiaRESUMO
We investigated whether likely pathogenic variants co-segregating with gastroschisis through a family-based approach using bioinformatic analyses were implicated in body wall closure. Gene Ontology (GO)/Panther functional enrichment and protein-protein interaction analysis by String identified several biological networks of highly connected genes in UGT1A3, UGT1A4, UGT1A5, UGT1A6, UGT1A7, UGT1A8, UGT1A9, UGT1A10, AOX1, NOTCH1, HIST1H2BB, RPS3, THBS1, ADCY9, and FGFR4. SVS-PhoRank identified a dominant model in OR10G4 (also as heterozygous de novo), ITIH3, PLEKHG4B, SLC9A3, ITGA2, AOX1, and ALPP, including a recessive model in UGT1A7, UGT1A6, PER2, PTPRD, and UGT1A3. A heterozygous compound model was observed in CDYL, KDM5A, RASGRP1, MYBPC2, PDE4DIP, F5, OBSCN, and UGT1A. These genes were implicated in pathogenetic pathways involving the following GO related categories: xenobiotic, regulation of metabolic process, regulation of cell adhesion, regulation of gene expression, inflammatory response, regulation of vascular development, keratinization, left-right symmetry, epigenetic, ubiquitination, and regulation of protein synthesis. Multiple background modifiers interacting with disease-relevant pathways may regulate gastroschisis susceptibility. Based in our findings and considering the plausibility of the biological pattern of mechanisms and gene network modeling, we suggest that the gastroschisis developmental process may be the consequence of several well-orchestrated biological and molecular mechanisms which could be interacting with gastroschisis predispositions within the first ten weeks of development.
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Parede Abdominal/patologia , Biologia Computacional/métodos , Gastrosquise/genética , Variação Genética , Ontologia Genética , Humanos , Padrões de Herança/genética , Mapas de Interação de Proteínas/genética , RecidivaRESUMO
BACKGROUND: Genes involved in gastroschisis have shown a strong interaction with environmental factors. However, less is known about its influence. We aimed to systematically review the genetic associations of gastroschisis, to summarize whether its genetic susceptibility has been restricted to the interaction with the environment, and to identify significant gaps that remain for consideration in future studies. METHODS: Genetic association studies of gastroschisis published 1980-2017 (PubMed/MEDLINE) were independently searched by two reviewers. Significant SNP-gastroschisis associations were grouped into crude and stratified risks, whereas SNPs were assessed from two or more independent studies. Frequencies, odds ratios, and 95% confidence intervals were pooled using descriptive analysis and Chi-square test accounting for heterogeneity. RESULTS: Seven eligible articles capturing associations of 14 SNPs from 10 genes for crude risk (including 10 and 4 SNPs with increased and decreased risk, respectively) and 30 SNPs from 14 genes for stratified risk in gastroschisis (including 37 and 14 SNPs with increased and decreased risk, respectively) were identified (Fisher's exact test, P = 0.438). The rs4961 (ADD1), rs5443 (GNB3), rs1042713, and rs1042714 (ADRB2) were significantly associated with gastroschisis. CONCLUSIONS: Genetic susceptibility in gastroschisis is not restricted to the interaction with the environment and should not be too narrowly focused on environmental factors. We found significant associations with four SNPs from three genes related to blood pressure regulation, which supports a significant role of vascular disruption in the pathogenesis of gastroschisis. Future studies considering gene-gene or gene-environmental interactions are warranted for better understanding the etiology of gastroschisis.
Assuntos
Meio Ambiente , Gastrosquise/genética , Predisposição Genética para Doença , Variação Genética , HumanosRESUMO
STUDY OBJECTIVE: To explore the prevalence, mortality, and spatial distribution of gastroschisis using a large population-based sample with cases identified according to birth and death certificates (ICD-10 diagnosis code Q79.3, gastroschisis) through the General Directorate of Health Information of the Secretary Health of Mexico, over the course of a 15-year period. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: A descriptive study examining 10,287 cases of gastroschisis was performed from 2000-2014 using public natality data for denominators (more than 25 million live births). Gastroschisis prevalence and mortality was calculated for each of year, state, maternal, and newborn characteristics. Spatial distribution was analyzed according to gastroschisis prevalence in the 32 states of Mexico. RESULTS: Gastroschisis prevalence was 4.01 per 10,000 live births (annual trend 2.09-6.85). Mortality associated with gastroschisis was 1.28 per 10,000 live births. Women younger than 20 years old, primiparae, and preterm infants had the highest gastroschisis-related prevalence (13.12, 5.83, and 7.51 per 10,000 live births, respectively). Gastroschisis prevalence and mortality did not differ according to newborn sex. A negative binomial distribution, variance (82,391.87) greater than the mean (321.47) was identified. CONCLUSION: Our findings show an increasing temporal trend for gastroschisis since 2000 in Mexico. Additionally, gastroschisis might follow in future instances a positive binomial or Poisson distribution. Therefore, improving surveillance of risk factors and supporting research for gastroschisis is warranted among maternal age younger than 25, particularly, younger than 20 years of age.
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Gastrosquise/epidemiologia , Adulto , Bases de Dados Factuais , Demografia , Feminino , Gastrosquise/mortalidade , Humanos , Lactente , Recém-Nascido , Masculino , México/epidemiologia , Gravidez , Prevalência , Fatores de RiscoRESUMO
PURPOSE: There is uncertainty over whether familial recurrences in gastroschisis might be higher. Moreover, scant information is available regarding its sociodemographic features. We aim to explore the recurrence risk, sex-dependent influence, and geographical distribution of familial gastroschisis. METHODS: A systematic review of the literature and data extraction from population-based studies published 1970-2017 (PubMed/MEDLINE) was independently performed by two reviewers. Familial ocurrence of gastroschisis, whereas sociodemographic features from 11 studies were pooled including 862 probands as a base. A descriptive analysis and Chi-square test were performed. RESULTS: Twenty-four probands had a positive family history of gastroschisis including 49 affected family members, for a recurrence risk of 5.7 and 3% adjusted for proband. Siblings' recurrence was 4.3%. Sex-dependent influence analysis (n = 879, from three studies) evidenced an increased susceptibility to gastroschisis in males (2.5%) compared to females (1.3%) adjusted for proband. Heterogeneity was identified by Fisher's exact test (P = 0.023). CONCLUSION: Our findings support a greater liability attributable to familial factors on gastroschisis along with significant information for family and prenatal counseling. We suggest that future studies should include for a more accurate account for both familial and environmental confounding factors to uncover relatives and environmental exposures that more limited family histories may have missed.
Assuntos
Gastrosquise/genética , Predisposição Genética para Doença , Gastrosquise/epidemiologia , Humanos , Recidiva , Risco , Fatores Sexuais , IrmãosRESUMO
PURPOSE: To evaluate the occurrence of gastroschisis attributable to familial factors in a Mexican population-based setting. METHODS: A descriptive study was performed among gastroschisis cases born from 2010 through 2016 at Tijuana General Hospital (Baja California, Mexico) to generate multigenerational pedigrees. RESULTS: There were 87 gastroschisis cases from 57,217 live births. Six probands (6.9%) had another affected family member. Two half-siblings, a set of monozygotic twins, a mother-and-daughter occurrence, a distant paternal cousin and a distant maternal uncle were identified. Sibling recurrence was 5.5%. From 174 males and 153 females studied (n=327, involving 180 nuclear families), sex-dependent influence analysis evidenced an increased susceptibility to gastroschisis in males (3.2%) compared to females (1.8%) with an overall of 2.5% adjusted for proband. CONCLUSIONS: Our results provide a greater liability attributable to familial factors on gastroschisis. In spite of the predominant sporadic occurrence, underlying genetic susceptibility and environmental influences point to a complex interplay between genes and environmental factors in gastroschisis. LEVEL OF EVIDENCE: Level IV.
Assuntos
Gastrosquise/epidemiologia , Gastrosquise/genética , Predisposição Genética para Doença , Família , Feminino , Humanos , Masculino , México/epidemiologia , Linhagem , Gravidez , Fatores de Risco , Gêmeos MonozigóticosRESUMO
In 1980 Smithells et al. reported that the intake of folic acid (FA) prevents the recurrence of neural tube defects (NTDs) [1]. After this and several other studies were conducted, the intake of 400 micrograms of folic acid per day, at least three months before and three months during pregnancy for prevention of NTD, was proposed [2,3,4]. Other strategies were also developed to increase folate blood levels in woman of childbearing age such as promoting the consumption of folate rich foods and food fortification (flour and most recently rice) [5]. Nevertheless, results have not been as expected due to poor consumption of folic acid supplements [6]. As a result, in the year 2000, a novel strategy was developed in order to increase folate blood levels in Mexican women. The results of the strategy are presented, as well as, a discussion about how to personalize a program for different populations.
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Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Defeitos do Tubo Neural/prevenção & controle , Cuidado Pré-Natal/métodos , Prevenção Primária/métodos , Complexo Vitamínico B/administração & dosagem , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Ácido Fólico/uso terapêutico , Humanos , México , Projetos Piloto , Gravidez , Complexo Vitamínico B/uso terapêuticoRESUMO
INTRODUCTION: Preterm birth is the most important cause of neonatal mortality and morbidity. It is a multifactorial disease with different etiologies, including genetic factors. Genetic variability is represented by single nucleotide polymorphisms (SNPs) in genes of proteins involved in the contractile activity. We determine the association between SNP 12109G> A in REN associated with preterm birth and premature rupture of membrane. MATERIALS AND METHODS: A study of cases ( N=112, 22-36 weeks of gestation; mean: 31, 95% confidence interval 30.7-32.2) and controls ( N=66; 38-40 weeks of gestation from the last menstrual period; mean: 39.8, 95% confidence interval 38.9-39.4) was performed. Genomic DNA was isolated in all patients from peripheral blood. The SNP 12109G> A ( Mbo I) in REN was typified by PCR-restriction fragment length polymorphism. RESULTS: A significant difference in the case group for the SNP 12109G>A was observed. The A allele was increased in women with preterm birth (81% cases vs. 15% control, p<0.0000004). There was also a significant difference between genotypes, mainly an excess of G/A heterozygotes in women with preterm birth (60% cases vs. 23% controls). The phenotype 12109G> A has odds ratio 6.62 (95% confidence interval 3.14-14.15), which means a high risk of preterm birth/premature rupture of membrane in presence of allele A, both in homozygotes and in heterozygotes. CONCLUSION: Allelic frequency of A of SNP 12109G>A was higher in women with preterm birth than in women with normal vaginal delivery and could be considered a risk factor.
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Estudos de Associação Genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único/genética , Nascimento Prematuro/genética , Renina/genética , Alelos , Estudos de Casos e Controles , Eletroforese em Gel de Poliacrilamida , Humanos , Fenótipo , Fatores de RiscoRESUMO
INTRODUCTION: The consumption of marijuana (exogenous cannabinoid) almost doubled in adults during last decade. Consumption of exogenous cannabinoids interferes with the endogenous cannabinoid (or "endocannabinoid" (eCB)) system (ECS), which comprises N-arachidonylethanolamide (anandamide, AEA), 2-arachidonoyl glycerol (2-AG), endocannabinoid receptors (cannabinoid receptors 1 and 2 (CB1R and CB2R), encoded by CNR1 and CNR2, respectively), and synthesizing/degrading enzymes (FAAH, fatty-acid amide hydrolase; MAGL, monoacylglycerol lipase; DAGL-α, diacylglycerol lipase-alpha). Reports regarding the toxic and therapeutic effects of pharmacological compounds targeting the ECS are sometimes contradictory. This may be caused by the fact that structure of the eCBs varies in the species studied. OBJECTIVES: First: to clone and characterize the cDNAs of selected members of ECS in a non-human primate (baboon, Papio spp.), and second: to compare those cDNA sequences to known human structural variants (single nucleotide polymorphisms and haplotypes). MATERIALS AND METHODS: Polymerase chain reaction-amplified gene products from baboon tissues were transformed into Escherichia coli. Amplicon-positive clones were sequenced, and the obtained sequences were conceptually translated into amino-acid sequences using the genetic code. RESULTS: Among the ECS members, CNR1 was the best conserved gene between humans and baboons. The phenotypes associated with mutations in the untranslated regions of this gene in humans have not been described in baboons. One difference in the structure of CNR2 between humans and baboons was detected in the region with the only known clinically relevant polymorphism in a human receptor. All of the differences in the amino-acid structure of DAGL-α between humans and baboons were located in the hydroxylase domain, close to phosphorylation sites. None of the differences in the amino-acid structure of MAGL observed between baboons and humans were located in the area critical for enzyme function. CONCLUSION: The evaluation of the data, obtained in non-human primate model of cannabis-related developmental exposure should take into consideration possible evolutionary-determined species-specific differences in the CB1R expression, CB2R transduction pathway, and FAAH and DAGLα substrate-enzyme interactions.
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Endocanabinoides/genética , Modelos Animais , Pesquisa Translacional Biomédica , Amidoidrolases/genética , Animais , Humanos , Lipase Lipoproteica/genética , Fígado/metabolismo , Monoacilglicerol Lipases/genética , Papio , Receptor CB1 de Canabinoide/genética , Receptor CB2 de Canabinoide/genética , Especificidade da EspécieRESUMO
Aarskog-Scott syndrome (AAS), also known as faciogenital dysplasia (FGD, OMIM # 305400), is an X-linked disorder of recessive inheritance, characterized by short stature and facial, skeletal, and urogenital abnormalities. AAS is caused by mutations in the FGD1 gene (Xp11.22), with over 56 different mutations identified to date. We present the clinical and molecular analysis of four unrelated families of Mexican origin with an AAS phenotype, in whom FGD1 sequencing was performed. This analysis identified two stop mutations not previously reported in the literature: p.Gln664* and p.Glu380*. Phenotypically, every male patient met the clinical criteria of the syndrome, whereas discrepancies were found between phenotypes in female patients. Our results identify two novel mutations in FGD1, broadening the spectrum of reported mutations; and provide further delineation of the phenotypic variability previously described in AAS.
RESUMO
The family observed in this study included affected males and asymptomatic females. The patients shared specific digital abnormalities including postaxial polydactyly, cutaneous syndactyly, and brachydactyly. In addition, the patients exhibited mild-to-moderate intellectual disability and short stature coupled with microbrachycephaly, scoliosis, and cerebellar and renal hypoplasia. No chromosomal alterations or copy number variations were found in the index case. The genetic linkage analysis, which focused on the X chromosome, and the haplotype analysis detected a ~15.74 Mb candidate region located at Xp11.4-p11.21 with a LOD score of 4.8. Additionally, half of the mothers showed skewed X-inactivation, while the other mothers exhibited random inactivation patterns. The candidate region includes 28 protein-encoding genes that have not yet been implicated in human disorders. We speculate that the observed phenotype is compatible with a monogenic disorder in which the mutant gene plays a significant role during embryonic development. Based on the patients' clinical features, image studies, pedigree, chromosome location, and X-inactivation studies in the mothers, we propose that this family has a novel, specific syndrome with an X-linked recessive mode of inheritance.
Assuntos
Anormalidades Múltiplas/genética , Cromossomos Humanos X , Nanismo/genética , Dedos/anormalidades , Deficiência Intelectual/genética , Dedos do Pé/anormalidades , Anormalidades Múltiplas/diagnóstico , Adulto , Mapeamento Cromossômico , Diagnóstico Diferencial , Nanismo/diagnóstico , Feminino , Genes Recessivos , Genes Ligados ao Cromossomo X , Haplótipos , Humanos , Deficiência Intelectual/diagnóstico , Escore Lod , Masculino , México , Pessoa de Meia-Idade , Técnicas de Diagnóstico Molecular , Linhagem , Fenótipo , Inativação do Cromossomo X , Adulto JovemRESUMO
OBJECTIVE: To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. MATERIAL AND METHODS: From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. RESULTS: A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. CONCLUSIONS: The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate of 0.22%. The program permitted the identification of metabolic disorders in the newborn, allowing an early intervention and prevention of life-threatening events and permanent neurological damage.
Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Espectrometria de Massas em Tandem , Humanos , Recém-Nascido , México , Triagem Neonatal/métodos , Fatores de TempoRESUMO
OBJETIVO: Instituir un programa estatal de tamizaje neonatal ampliado para identificar errores innatos del metabolismo y determinar su prevalencia en la población de recién nacidos del estado de Nuevo León. MATERIAL Y MÉTODOS: Entre marzo de 2002 y febrero de 2004 se incluyeron neonatos consecutivos nacidos en hospitales públicos del estado. Se colectaron muestras de sangre en papel filtro entre las 24 y 48 horas de vida y se las sometió a tamiz metabólico mediante espectrometría de masas en tándem. RESULTADOS: Se analizaron 42 264 primeras muestras y se detectaron siete casos, uno de cada padecimiento: homocistinuria, fenilcetonuria, citrulinemia, tirosinemia/transitoria, deficiencia de 3-metilcrotonil-CoA carboxilasa, deficiencia de 3-hidroxi-3-metilglutaril-CoA liasa y galactosemia típica. CONCLUSIONES: La incidencia acumulada de defectos metabólicos en la población fue de 1:5 000 con 0.22 por ciento de casos falso-positivos. El programa permitió identificar y tratar con oportunidad los trastornos metabólicos al nacimiento con una efectiva prevención secundaria del retraso mental.
OBJECTIVE: To initiate a statewide expanded metabolic screening program in neonates with the purpose of identifying the most common inborn errors of metabolism. MATERIAL AND METHODS: From March 2002 through February 2004, a blood sample was obtained between 24 and 48 hours after delivery from every consecutive child born in public hospitals in Nuevo León. It was spotted on filter paper and analyzed by tandem mass spectrometry for expanded metabolic screening. RESULTS: A total of 42 264 samples were analyzed. Were obtained seven positive results, one for each disorder: homocystinuria, hyperphenylalaninemia, citrulinemia, transient tyrosinemia, 3-methylcrotonyl CoA carboxylase deficiency, 3-hydroxy-3-methylglutaryl CoA deficiency, and classic galactosemia. CONCLUSIONS: The estimated incidence of inborn errors of metabolism is 1:5 000, with a false positive rate of 0.22 percent. The program permitted the identification of metabolic disorders in the newborn, allowing an early intervention and prevention of life-threatening events and permanent neurological damage.
Assuntos
Humanos , Recém-Nascido , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Espectrometria de Massas em Tandem , México , Triagem Neonatal/métodos , Fatores de TempoRESUMO
OBJECTIVE: In 1999, a folic acid campaign for prevention of neural tube defects was started in Nuevo León, México, with the recommendation of taking a 5000 -mcg tablet of folic acid per week. The purpose of this study was to compare the epidemiology of neural tube defects after four years of the campaign. METHODS: Cases of anencephaly, spina bifida, and encephalocele (ICD Q00, Q01, Q05, 10th Ed.) from public and private hospitals were registered by immediate notification, death certificates, and fetal death registries. Comparisons of neural tube defects rates, phenotype distribution of cases, and sex ratios, registered before and after the folic acid campaign, were done using the Student's t Test and Chi square test. RESULTS: There was a 50% reduction in the incidence of anencephaly and spina bifida cases from 93 in 1999 (1.04x1000) to 46 in the year 2003 (0.56x1000) (p<0.001). Spina bifida cases declined up to 70% in 2002 and anencephaly cases up to 50% in 2003. In 1999, overall, the ratio (females: males) was 0.66 with female excess; the sex ratio was similar for anencephaly and spina bifida cases. In the year 2000, female cases showed a significant reduction for both spina bifida and anencephaly (75% and 56% respectively); the sex ratio was 0.57 with a greater male excess for both phenotypes. CONCLUSIONS: Weekly administration of 5000 mcg of folic acid reduces the incidence of neural tube defects 50%, primarily spina bifida, with a higher reduction of female cases.