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INTRODUCTION: Tyrosinemia type 1 is a rare disease with autosomal recessive inheritance, featuring various clinical manifestations. These may encompass acute neonatal liver failure, neonatal cholestatic syndrome, chronic hepatitis, cirrhosis, hepatocellular carcinoma, and, alternatively, kidney disorders like renal tubular acidosis, Fanconi syndrome, hypophosphatemic rickets, among other alterations. Diagnosis relies on detecting toxic metabolites in the blood and urine, ideally confirmed through molecular testing. METHOD: A consensus was reached with experts in the field of inborn errors of metabolism (EIM), including eight pediatric gastroenterologists, two EIM specialists, two geneticists, three pediatric nutritionists specialized in EIM, and a pediatric surgeon specializing in transplants. Six working groups were tasked with formulating statements and justifications, and 32 statements were anonymously voted on using the Likert scale and the Delphi method. The first virtual vote achieved an 80% consensus, with the remaining 20% determined in person. RESULTS: The statements were categorized into epidemiology, clinical presentation, diagnosis, nutritional and medical treatment, and genetic counseling. CONCLUSIONS: This consensus serves as a valuable tool for primary care physicians, pediatricians, and pediatric gastroenterologists, aiding in the prompt diagnosis and treatment of this disease. Its impact on the morbidity and mortality of patients with tyrosinemia type 1 is substantial.
INTRODUCCIÓN: La tirosinemia tipo 1 es una enfermedad rara, con herencia autosómica recesiva, con múltiples manifestaciones clínicas, que pueden comprender desde falla hepática aguda neonatal, síndrome colestásico neonatal, hepatitis crónica, cirrosis o hepatocarcinoma, hasta alteraciones renales como acidosis tubular renal, síndrome de Fanconi o raquitismo hipofosfatémico, entre otras. El diagnóstico se basa en la presencia de metabolitos tóxicos en la sangre y la orina, idealmente con la confirmación molecular de la enfermedad. MÉTODO: Se realizó un consenso con expertos en el área de los errores innatos del metabolismo (EIM): ocho gastroenterólogos pediatras, dos médicos especialistas en EIM, dos genetistas, tres nutriólogas pediatras especializadas en EIM y un cirujano pediatra especialista en trasplantes. Se formaron seis mesas de trabajo encargadas de desarrollar los enunciados con sus justificaciones y fueron votados anónimamente 32 enunciados en una escala Likert con un método Delphi. La primera votación fue virtual, obteniendo consenso del 80% de los enunciados, y la segunda fue presencial, obteniendo el 20% restante. RESULTADOS: Los enunciados fueron divididos en epidemiología, cuadro clínico, diagnóstico, tratamiento nutricional y médico, y consejo genético. CONCLUSIONES: Este consenso constituye una valiosa herramienta para los médicos de atención primaria, pediatras y gastroenterólogos pediátricos, ya que ayuda a diagnosticar y tratar rápidamente esta enfermedad. Su impacto en la morbilidad y mortalidad de los pacientes con tirosinemia tipo 1 es sustancial.
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Consenso , Tirosinemias , Humanos , Tirosinemias/diagnóstico , Tirosinemias/terapia , México , Recém-Nascido , Técnica Delphi , Aconselhamento GenéticoRESUMO
Propionate defects (PDs) mainly include methylmalonic (MMA) and propionic acidemia (PA) defects. Lifelong PD patients progress from the compensated to the decompensated stages, the latter of which are characterized by life-threatening acidemia and hyperammonemia crises. PD patients can suffer immunocompromise, especially during the decompensation stage. There is a significant gap in the research regarding the humoral immune response in PD patients. Here, we analyzed serum immunoglobulin concentrations and hemograms across compensated and decompensated stages in PD patients. Nutritional status and crisis triggers of decompensation were also explored. Twenty patients were studied, and 25 decompensation events (DE) and 8 compensation events (CE) were recorded. Compared with those in the CE group, the IgG levels in the DE group (513.4 ± 244.5 mg/dL) were significantly lower than those in the CE group (860.8 ± 456.5 mg/dL) (p < 0.0087). The mean hemoglobin concentration was significantly lower in the DE group (11.8 g/dL) than in the CE group (13.4 g/dL) (p < 0.05). The most frequent (48%) possible decompensation trigger factor was infection. Most of the events were registered in eutrophic patients (87.9%), despite which 65.2% and 50% of patients who experienced decompensated and compensated events, respectively, presented with hypogammaglobulinemia G. These findings provide evidence of the immunodeficiency of PD patients, independent of their nutritional status. We suggest that PD patients be managed as immunocompromised independently of their nutritional status or metabolic state (compensated or decompensated).
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Agamaglobulinemia , Estado Nutricional , Humanos , Masculino , Feminino , Agamaglobulinemia/sangue , Agamaglobulinemia/imunologia , Agamaglobulinemia/complicações , Pessoa de Meia-Idade , Idoso , Imunoglobulina G/sangue , Adulto , Propionatos/sangue , Acidemia PropiônicaRESUMO
Introduction: Congenital glucose-galactose malabsorption (CGGM) is a rare autosomal recessive disorder that primarily causes chronic intractable diarrhea. This study aims to describe the clinical history, laboratory profile, diagnostic workflow, and management of the first patient reported with CGGM in Mexico. Methods: The case involves a Mexican female infant with recurrent admissions to the emergency room since birth due to chronic diarrhea. Results: The infant was born at term by C-section with a birth weight of 3.120â kg and height of 48â cm for consanguineous parents. She had been breastfed until day 5 of her life when she presented lethargy, diarrhea, abdominal discomfort, and jaundice. During the first evaluation at the emergency room, the significant laboratory finding was blood tyrosine elevation; afterward, amino acid and succinylacetone determinations were obtained, discarding tyrosinemia. When admitted to the hospital, an abdominal ultrasound detected a duplex collecting system. At this time, rice formula was introduced to the patient. She was discharged with jaundice improvement, but diarrhea persisted. Several formula changes had been made from rice to extensively hydrolyzed casein protein to whey-based, with no clinical improvement; the patient still had 10-12 excretions daily. In the second hospitalization, the patient presented anemia, severe dehydration, hyperammonemia, and renal tubular acidosis. A next-generation sequencing panel for inborn errors of metabolism and congenital diarrhea was performed, identifying a homozygous variant in SLC5A1 (c.1667T > C). The diagnosis of CGGM was made at 3 months of age. The infant was initially treated with a modular galactose-glucose-free formula with oil, fructose, casein, minerals, and vitamins until a commercial fructose-based formula was introduced. This led to a complete resolution of diarrhea and improved nutritional status. Discussion: Diagnosing CGGM is challenging for clinicians, and next-generation sequencing is a valuable tool for providing appropriate treatment. More detailed information on patients with this condition might lead to possible phenotype-genotype correlations. This case's primary clinical and biochemical findings were chronic diarrhea, anemia, jaundice, renal tubular acidosis, hyperammonemia, and initial hypertyrosinemia. Symptoms were resolved entirely with the fructose-based formula.
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Objective: To characterize adherence to Phenylketonuria (PKU) management practices among PKU patients treated at reference sites around Argentina, Brazil, and Mexico. Methods: This is a retrospective, observational, multicenter, and multinational survey-based study using aggregate data. From an initial list of 40 sites, 22 clinicians expressed interest in completing the survey, with 20 clinicians from 20 unique sites fulfilling all the study criteria. The Survey contained 28 questions, including respondent's clinic characteristics, clinic PKU treatment recommendations, and patient adherence to clinic recommendations. Survey was available in local languages, and the respondents were asked to consult their clinic records to complete their responses. Adherence was assessed by target blood phenylalanine (Phe), target blood testing frequency, and clinic visits. Results: A total of 1077 (out of 1377) actively managed PKU patients (seen in the clinic in the last 3 years) from 13 clinics in Brazil, six in Argentina, and one in Mexico were analyzed. Upper blood Phe target was set over 360 µMol/L in 70% of the clinics for adult patients. Around 40% of the patients >30 years old had Phe blood tests done twice a year or less, with 60% of the clinics recommending semestral visits for adults <30 years old. Twice a month was the most common frequency of visits for <1 year old. The COVID-19 pandemic was a disruptor for frequency of visits and exams. Conclusions: These results show that there is still room for improvement in terms of adherence, namely in adults and older children. More efforts must be made to educate patients and healthcare professionals about the importance of treatment adherence, accompanied by public policies that expand access to pharmacological and dietary treatment with diversity and quality to improve adherence to adequate blood Phe levels.
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Hyperphenylalaninemia (HPA), which includes phenylketonuria (PKU), is a genetic autosomal recessive disorder arising from a deficiency in the enzyme named phenylalanine hydroxylase (PAH). Affected patients can experience severe and irreversible neurological impairments when phenylalanine (Phe) blood concentration exceeds 360 µmol/L (6 mg/dL). Here, we describe a female HPA patient who was born in Mexico to Cuban non-consanguineous parents and identified by newborn screening, and who bears the previously unreported PAH NM_000277.3(PAH):c.[229T>C];[1222C>T] or p.[Tyr77His];[Arg408Trp] genotype. At diagnosis, the patient showed a Phe blood level of 321 µmol/L (5.3 mg/dL), indicative of mild HPA. Neither of the PAH variants found in this patient had been previously reported in the mutational PAH spectrum of the Mexican population. The c.229T>C or p.(Tyr77His) PAH variant was previously related to mild HPA in the Swedish population. Our in silico structural analysis and molecular docking showed that mutated His 77 residue is located in the allosteric site of PAH at the interface of the two monomers. The PDBsum in silico tool predicted that this variant would cause minimal structural disturbance of the protein interface in the presence of Phe at the allosteric site. Docking studies revealed that these structural changes might be attenuated by the allosteric effect of Phe. Given the classic PKU phenotype conditioned by the "Celtic" or c.[1222C>T] or p.(Arg408Trp) PAH variant, which is the second variant in this patient, we propose that p.(Tyr77His) has a hypomorphic feature that could explain her mild HPA phenotype. Our results show the importance of following up on cases detected by NBS and the value of genetic studies and in silico tools that aid in the establishment of correct therapeutic strategies.
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Advances in an early diagnosis by expanded newborn screening (NBS) have been achieved mainly in developed countries, while populations of middle- and low-income countries have poor access, leading to disparities. Expanded NBS in Mexico is not mandatory. Herein, we present an overview of the differences and unmet NBS needs of a group of Mexican patients with inborn errors of intermediary metabolism (IEiM), emphasizing the odyssey experienced to reach a diagnosis. We conducted a retrospective observational study of a historical cohort of patients with IEiM from a national reference center. A total of 924 patients with IEiM were included. Although 72.5% of the diseases identified are detectable by expanded NBS, only 35.4% of the patients were screened. The mortality in the unscreened group was almost two-fold higher than that in the screened group. Patients experienced a median diagnostic delay of 4 months, which is unacceptably long considering that to prevent disability and death, these disorders must be treated in the first days of life. Patients had to travel long distances to our reference center, contributing to their unacceptable diagnostic odyssey. This study highlights the urgent need to have an updated, expanded NBS program with adequate follow up in Mexico and promote the creation of regional medical care centers. We also provide compelling evidence that could prove valuable to decision makers overseeing public health initiatives for individuals impacted by IEiM from middle- and low-income countries.
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BACKGROUND/PURPOSE(S): During a viral infection, the immune response is mediated by the toll-like receptors and myeloid differentiation Factor 88 (MyD88) that play an important role sensing infections such as SARS-CoV-2 which has claimed the lives of more than 6.8 million people around the world. METHODS: We carried out a cross-sectional with a population of 618 SARS-CoV-2-positive unvaccinated subjects and further classified based on severity: 22% were mild, 34% were severe, 26% were critical, and 18% were deceased. Toll Like Receptor 7 (TLR7) single-nucleotide polymorphisms (rs3853839, rs179008, rs179009, and rs2302267) and MyD88 (rs7744) were genotyped using TaqMan OpenArray. The association of polymorphisms with disease outcomes was performed by logistic regression analysis adjusted by covariates. RESULTS: A significant association of rs3853839 and rs7744 of the TLR7 and MyD88 genes, respectively, was found with COVID-19 severity. The G/G genotype of the rs3853839 TLR7 was associated with the critical outcome showing an Odd Ratio = 1.98 (95% IC = 1.04-3.77). The results highlighted an association of the G allele of MyD88 gene with severe, critical and deceased outcomes. Furthermore, in the dominant model (AG + GG vs. AA), we observed an Odd Ratio = 1.70 (95% CI = 1.02-2.86) with severe, Odd Ratio = 1.82 (95% CI = 1.04-3.21) with critical, and Odd Ratio = 2.44 (95% CI = 1.21-4.9) with deceased outcomes. CONCLUSION: To our knowledge this work represents an innovative report that highlights the significant association of TLR7 and MyD88 gene polymorphisms with COVID-19 outcomes and the possible implication of the MyD88 variant with D-dimer and IFN-α concentrations.
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COVID-19 , Receptor 7 Toll-Like , Humanos , Receptor 7 Toll-Like/genética , Receptor 7 Toll-Like/metabolismo , Predisposição Genética para Doença , Fator 88 de Diferenciação Mieloide/genética , Estudos Transversais , COVID-19/genética , SARS-CoV-2 , Genótipo , Polimorfismo de Nucleotídeo Único/genéticaRESUMO
BACKGROUND: Gestational diabetes mellitus (GDM) represents the main metabolic alteration during pregnancy. The available methods for diagnosing GDM identify women when the disease is established, and pancreatic beta-cell insufficiency has occurred.The present study aimed to generate an early prediction model (under 18 weeks of gestation) to identify those women who will later be diagnosed with GDM. METHODS: A cohort of 75 pregnant women was followed during gestation, of which 62 underwent normal term pregnancy and 13 were diagnosed with GDM. Targeted metabolomics was used to select serum biomarkers with predictive power to identify women who will later be diagnosed with GDM. RESULTS: Candidate metabolites were selected to generate an early identification model employing a criterion used when performing Random Forest decision tree analysis. A model composed of two short-chain acylcarnitines was generated: isovalerylcarnitine (C5) and tiglylcarnitine (C5:1). An analysis by ROC curves was performed to determine the classification performance of the acylcarnitines identified in the study, obtaining an area under the curve (AUC) of 0.934 (0.873-0.995, 95% CI). The model correctly classified all cases with GDM, while it misclassified ten controls as in the GDM group. An analysis was also carried out to establish the concentrations of the acylcarnitines for the identification of the GDM group, obtaining concentrations of C5 in a range of 0.015-0.25 µmol/L and of C5:1 with a range of 0.015-0.19 µmol/L. CONCLUSION: Early pregnancy maternal metabolites can be used to screen and identify pregnant women who will later develop GDM. Regardless of their gestational body mass index, lipid metabolism is impaired even in the early stages of pregnancy in women who develop GDM.
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The relationship between protein and energy and their appropriate proportions in hyperphenylalaninemia (HPA) or phenylketonuria (PKU) patients in terms of growth have been poorly studied, especially in those diagnosed late. We aimed to describe the protein energy ratio (P:E) and its association with body mass index (BMI) in 638 dietetic and anthropometric assessments from 54 early- or late-diagnosed HPA/PKU patients. Dietetic and anthropometric data were analyzed and classified according to BMI Z-Score and type of diagnosis, early by newborn screening (NBS) or late. Correlation between BMI Z-Score and P:E ratio was established. Percent of dietary protein from Phe-free metabolic formula was analyzed. According to the BMI Z-Score, the majority of assessments were eutrophic (69.4%). The median P:E ratio was >4 in most of the overweight assessments. Remarkably, the underweight group consumed the highest proportion of Phe-free metabolic formula (74.5%). A positive correlation between BMI Z-Score and P:E ratio was found. The highest proportion of underweight was found in the late-diagnosed patients. Our findings might be related to their nutritional history previous to the HPA/PKU treatment. Thus, complex nutritional outcome of the late-diagnosed HPA/PKU patients deserves actions to guarantee the early diagnosis, closer nutritional follow-up and alternative therapeutic approaches.
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Fenilcetonúrias , Magreza , Recém-Nascido , Humanos , Índice de Massa Corporal , México , Fenilcetonúrias/diagnóstico , Peso CorporalRESUMO
Severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection triggers inflammatory clinical stages that affect the outcome of patients with coronavirus disease 2019 (COVID-19). Disease severity may be associated with a metabolic imbalance related to amino acids, lipids, and energy-generating pathways. The aim of this study was to characterize the profile of amino acids and acylcarnitines in COVID-19 patients. A multicenter, cross-sectional study was carried out. A total of 453 individuals were classified by disease severity. Levels of 11 amino acids, 31 acylcarnitines, and succinylacetone in serum samples were analyzed by electrospray ionization-triple quadrupole tandem mass spectrometry. Different clusters were observed in partial least squares discriminant analysis, with phenylalanine, alanine, citrulline, proline, and succinylacetone providing the major contribution to the variability in each cluster (variable importance in the projection >1.5). In logistic models adjusted by age, sex, type 2 diabetes mellitus, hypertension, and nutritional status, phenylalanine was associated with critical outcomes (odds ratio=5.3 (95% CI 3.16-9.2) in the severe vs. critical model, with an area under the curve of 0.84 (95% CI 0.77-0.90). In conclusion the metabolic imbalance in COVID-19 patients might affect disease progression. This work shows an association of phenylalanine with critical outcomes in COVID-19 patients, highlighting phenylalanine as a potential metabolic biomarker of disease severity.
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COVID-19 , Diabetes Mellitus Tipo 2 , Humanos , SARS-CoV-2 , Estudos Transversais , Aminoácidos , FenilalaninaRESUMO
BACKGROUND: Newborn screening for glucose-6-phosphate dehydrogenase deficiency (G6PDd) was implemented in Mexico beginning in 2017. In a Mexican population, genotyping analysis of G6PD as a second-tier method identified a previously unreported missense variant, p.(Ser184Cys), which we propose to call "Toluca", and the extremely rare p.(Gln195His) or "Tainan" variant, which was previously described in the Taiwanese population as a Class II allele through in silico evaluations. Here, we sought to perform in vitro biochemical characterizations of the Toluca and Tainan G6PD natural variants and describe their associated phenotypes. METHODS: The "Toluca" and "Tainan" variants were identified in three unrelated G6PDd newborn males, two of whom lacked evidence of acute hemolytic anemia (AHA) or neonatal hyperbilirubinemia (NHB). We constructed wild-type (WT), Tainan, and Toluca G6PD recombinant enzymes and performed in vitro assessments. RESULTS: Both variants had diminished G6PD expression, decreased affinities for glucose-6-phosphate and NADP+ substrates, significant decreases in catalytic efficiency (â¼97 % with respect to WT-G6PD), and diminished thermostabilities that were partially rescued by NADP+. In silico protein modeling predicted that the variants would have destabilizing effects on the protein tertiary structure, potentially reducing the enzyme half-lives and/or catalytic efficiencies. CONCLUSION: Our data suggest that G6PD "Tainan" and "Toluca" are potential Class II natural variants, which agrees with the absence of chronic nonspherocytic hemolytic anemia (CNSHA) in our patients. It remains to be determined whether these variants represent high-risk genetic factors for developing CNSHA, AHA, and/or NHB.
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Deficiência de Glucosefosfato Desidrogenase , Humanos , Masculino , Recém-Nascido , Deficiência de Glucosefosfato Desidrogenase/diagnóstico , Deficiência de Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/química , Triagem Neonatal , NADP , MéxicoRESUMO
Metabolic syndrome (MetS) is a group of several metabolic conditions predisposing to chronic diseases. Individuals diagnosed with MetS are physiologically heterogeneous, with significant sex-specific differences. Therefore, we aimed to investigate the potential sex-specific serum modifications of amino acids and acylcarnitines (ACs) and their relationship with MetS in the Mexican population. This study included 602 participants from the Health Workers Cohort Study. Forty serum metabolites were analyzed using a targeted metabolomics approach. Multivariate regression models were used to test associations of clinical and biochemical parameters with metabolomic profiles. Our findings showed a serum amino acid signature (citrulline and glycine) and medium-chain ACs (AC14:1, AC10, and AC18:10H) associated with MetS. Glycine and AC10 were specific metabolites representative of discrimination according to sex-dependent MetS. In addition, we found that glycine and short-chain ACs (AC2, AC3, and AC8:1) are associated with age-dependent MetS. We also reported a significant correlation between body fat and metabolites associated with sex-age-dependent MetS. In conclusion, the metabolic profile varies by MetS status, and these differences are sex-age-dependent in the Mexican population.
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Síndrome Metabólica , Carnitina/análogos & derivados , Citrulina , Estudos de Coortes , Feminino , Glicina , Humanos , Masculino , MetabolômicaRESUMO
Inborn errors of intermediary metabolism (IEiM) are a group of monogenic disorders that affect a metabolic pathway of proteins, carbohidrates, or lipids; when not treated timely, IEiM are associated with high morbidity and mortality. To date, nutritional therapy is the cornerstone of treatment for patients with IEiM, which aims to prevent the accumulation of toxic metabolites by restricting the substrates involved in the affected pathway. Nutritional management in infants includes a metabolic formula free of the nutrients involved in IEiM and breastmilk or infant formula. Because of its amino acid profile, the content of essential fatty acids, and protection against disease, breast milk is an excellent food for patients with IEiM. This literature review on breastfeeding in some IEiM aims to serve as a guide for health care personnel involved in the medical care of these patients. Breastfeeding can be successfully carried out in patients with IEiM as long as there is a close and continuous follow-up, preferably in specialized centers. The nutrition professional and the pediatrician should individualize the recommendations to provide on-demand breastfeeding in conjunction with metabolic formula or quantified breastfeeding to achieve a good clinical evolution in this group of patients.
Los errores innatos del metabolismo intermediario (EIMi) son un grupo de enfermedades monogénicas que afectan alguna vía del metabolismo de las proteínas, los hidratos de carbono o los lípidos; cuando no son tratados a tiempo, se asocian con una elevada morbimortalidad. A la fecha, la piedra angular del tratamiento de los EIMi ha sido la terapia nutricional, cuyo propósito es evitar la acumulación de metabolitos tóxicos al restringir los sustratos que están involucrados en la vía afectada. El manejo nutricional en lactantes incluye una fórmula metabólica sin los nutrimentos involucrados en el EIMi más el aporte de alimentación al seno materno o fórmula infantil. Por el perfil de aminoácidos, la proporción de ácidos grasos esenciales y la protección contra enfermedades, la leche materna resulta un alimento ideal para los pacientes con EIMi. El objetivo de esta revisión de la literatura sobre la lactancia materna en algunos EIMi es servir de guía para el personal de salud involucrado en la atención médica de estos pacientes. La lactancia materna puede ser llevada a cabo de forma exitosa en pacientes con EIMi siempre que exista un seguimiento estrecho y continuo, de preferencia en centros especializados. El profesional de la nutrición y el pediatra deben individualizar las recomendaciones para proporcionar una lactancia a libre demanda en conjunto con una fórmula metabólica o una lactancia materna cuantificada, y con ello lograr una adecuada evolución en estos pacientes.
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Aleitamento Materno , Fórmulas Infantis , Feminino , Humanos , Lactente , Recém-NascidoRESUMO
Resumen Los errores innatos del metabolismo intermediario (EIMi) son un grupo de enfermedades monogénicas que afectan alguna vía del metabolismo de las proteínas, los hidratos de carbono o los lípidos; cuando no son tratados a tiempo, se asocian con una elevada morbimortalidad. A la fecha, la piedra angular del tratamiento de los EIMi ha sido la terapia nutricional, cuyo propósito es evitar la acumulación de metabolitos tóxicos al restringir los sustratos que están involucrados en la vía afectada. El manejo nutricional en lactantes incluye una fórmula metabólica sin los nutrimentos involucrados en el EIMi más el aporte de alimentación al seno materno o fórmula infantil. Por el perfil de aminoácidos, la proporción de ácidos grasos esenciales y la protección contra enfermedades, la leche materna resulta un alimento ideal para los pacientes con EIMi. El objetivo de esta revisión de la literatura sobre la lactancia materna en algunos EIMi es servir de guía para el personal de salud involucrado en la atención médica de estos pacientes. La lactancia materna puede ser llevada a cabo de forma exitosa en pacientes con EIMi siempre que exista un seguimiento estrecho y continuo, de preferencia en centros especializados. El profesional de la nutrición y el pediatra deben individualizar las recomendaciones para proporcionar una lactancia a libre demanda en conjunto con una fórmula metabólica o una lactancia materna cuantificada, y con ello lograr una adecuada evolución en estos pacientes.
Abstract Inborn errors of intermediary metabolism (IEiM) are a group of monogenic disorders that affect a metabolic pathway of proteins, carbohidrates, or lipids; when not treated timely, IEiM are associated with high morbidity and mortality. To date, nutritional therapy is the cornerstone of treatment for patients with IEiM, which aims to prevent the accumulation of toxic metabolites by restricting the substrates involved in the affected pathway. Nutritional management in infants includes a metabolic formula free of the nutrients involved in IEiM and breastmilk or infant formula. Because of its amino acid profile, the content of essential fatty acids, and protection against disease, breast milk is an excellent food for patients with IEiM. This literature review on breastfeeding in some IEiM aims to serve as a guide for health care personnel involved in the medical care of these patients. Breastfeeding can be successfully carried out in patients with IEiM as long as there is a close and continuous follow-up, preferably in specialized centers. The nutrition professional and the pediatrician should individualize the recommendations to provide on-demand breastfeeding in conjunction with metabolic formula or quantified breastfeeding to achieve a good clinical evolution in this group of patients.
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Preterm newborns are extremely vulnerable to morbidities, complications, and death. Preterm birth is a global public health problem due to its socioeconomic burden. Nurturing preterm newborns is a critical medical issue because they have limited nutrient stores and it is difficult to establish enteral feeding, which leads to inadequate growth frequently associated with poor neurodevelopmental outcomes. Parenteral nutrition (PN) provides nutrients to preterm newborns, but its biochemical effects are not completely known. To study the effect of PN treatment on preterm newborns, an untargeted metabolomic 1H nuclear magnetic resonance (NMR) assay was performed on 107 urine samples from 34 hospitalized patients. Multivariate data (Principal Component Analysis, PCA, Orthogonal partial least squares discriminant analysis OPLS-DA, parallel factor analysis PARAFAC-2) and univariate analyses were used to identify the association of specific spectral data with different nutritional types (NTs) and gestational ages. Our results revealed changes in the metabolic profile related to the NT, with the tricarboxylic acid cycle and galactose metabolic pathways being the most impacted pathways. Low citrate and succinate levels, despite higher glucose relative urinary concentrations, seem to constitute the metabolic profile found in the studied critically ill preterm newborns who received PN, indicating an energetic dysfunction that must be taken into account for better nutritional management.
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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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Mutação , Fenilalanina Hidroxilase/química , Fenilalanina Hidroxilase/genética , Fenilcetonúrias/genética , Análise de Sequência de DNA/métodos , Substituição de Aminoácidos , Domínio Catalítico , Feminino , Técnicas de Genotipagem , Humanos , Recém-Nascido , Mutação com Perda de Função , Masculino , México , Modelos Moleculares , Mutação de Sentido Incorreto , Triagem Neonatal , Conformação ProteicaRESUMO
According to the Iodine Global Network, Mexico is considered a country with adequate national iodine intake (297 mg/L), but some regions have not been studied. We aimed to evaluate urinary iodine concentration (UIC) and its association with thyroid stimulating hormone (TSH) levels and the nutritional status in 307 children (aged 5 to 11 years) from three elementary schools of Monterrey, northern Mexico. UIC in spot urine samples and capillary TSH levels were measured to assess thyroid function, in addition to weight, height, body mass index (BMI), and waist circumference (WC). We found a median UIC of 442 mg/L and a significant association between UIC and TSH levels by logistic regression when data were adjusted for (1) age and sex; (2) age, sex, and WC; and (3) age, sex, and weight status. UIC values were higher in 7-year-old children compared to 11-year-old children. High prevalences of overweight/obesity (41%) and WC >90 pctl (22%) were observed. This study identified higher UIC levels in children than those previously reported in the country. The UIC showed a positive and significant correlation between TSH levels in the three models evaluated. More studies are needed to assess the causes and possible outcomes of high UIC levels.
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Iodo/urina , Estado Nutricional , Tireotropina/sangue , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , México/epidemiologia , Obesidade/epidemiologia , Sobrepeso/epidemiologiaRESUMO
La fenilcetonuria y otras hiperfenilalaninemias son enfermedades genéticas cuya detección actualmente es obligatoria en México, tanto en el sector público como en el privado. La detección y el tratamiento oportunos han demostrado prevenir las manifestaciones neurológicas y la discapacidad que caracterizan esta enfermedad. Por ello, es de suma importancia que el pediatra y el personal de salud involucrados en la atención de estos pacientes conozcan, comprendan e implementen el manejo nutricional de manera correcta. Aunque existen varios tratamientos, el más utilizado es la restricción dietética de fenilalanina. El tratamiento nutricio incluye el uso de la llamada «fórmula médica¼ o «fórmula metabólica sin fenilalanina¼, la cual fue concebida desde el primer tercio del siglo XX. Posteriormente, se han realizado múltiples estudios y modificaciones con el fin de mejorar el pronóstico de los pacientes. El presente trabajo describe las principales características y diferencias entre las fórmulas libres de fenilalanina de seguimiento disponibles en México, para que el personal de salud cuente con elementos para su correcta prescripción.
Assuntos
Fenilcetonúrias , Humanos , México , Fenilcetonúrias/metabolismoRESUMO
BACKGROUND: Elevations of circulating branched-chain amino acids (BCAA) are observed in humans with obesity and metabolic comorbidities, such as insulin resistance. Although it has been described that microbial metabolism contributes to the circulating pool of these amino acids, studies are still scarce, particularly in pediatric populations. Thus, we aimed to explore whether in early adolescents, gut microbiome was associated to circulating BCAA and in this way to insulin resistance. METHODS: Shotgun sequencing was performed in DNA from fecal samples of 23 early adolescents (10-12 years old) and amino acid targeted metabolomics analysis was performed by LC-MS/MS in serum samples. By using the HUMAnN2 algorithm we explored microbiome functional profiles to identify whether bacterial metabolism contributed to serum BCAA levels and insulin resistance markers. RESULTS: We identified that abundance of genes encoding bacterial BCAA inward transporters were negatively correlated with circulating BCAA and HOMA-IR (P < 0.01). Interestingly, Faecalibacterium prausnitzii contributed to approximately ~ 70% of bacterial BCAA transporters gene count. Moreover, Faecalibacterium prausnitzii abundance was also negatively correlated with circulating BCAA (P = 0.001) and with HOMA-IR (P = 0.018), after adjusting for age, sex and body adiposity. Finally, the association between Faecalibacterium genus and BCAA levels was replicated over an extended data set (N = 124). CONCLUSIONS: We provide evidence that gut bacterial BCAA transport genes, mainly encoded by Faecalibacterium prausnitzii, are associated with lower circulating BCAA and lower insulin resistance. Based on the later, we propose that the relationship between Faecalibacterium prausnitzii and insulin resistance, could be through modulation of BCAA.
Assuntos
Aminoácidos de Cadeia Ramificada/sangue , Faecalibacterium prausnitzii/fisiologia , Microbioma Gastrointestinal , Adolescente , Fatores Etários , Aminoácidos de Cadeia Ramificada/metabolismo , Biomarcadores , Pesos e Medidas Corporais , Criança , Feminino , Humanos , Resistência à Insulina , Masculino , Metabolômica/métodos , Metagenoma , Metagenômica/métodos , Obesidade/metabolismo , Vigilância em Saúde PúblicaRESUMO
Recent evidence shows that obesity correlates negatively with bone mass. However, traditional anthropometric measures such as body mass index could not discriminate visceral adipose tissue from subcutaneous adipose tissue. The visceral adiposity index (VAI) is a reliable sex-specified indicator of visceral adipose distribution and function. Thus, we aimed to identify metabolomic profiles associated with VAI and low bone mineral density (BMD). A total of 602 individuals from the Health Workers Cohort Study were included. Forty serum metabolites were measured using the targeted metabolomics approach, and multivariate regression models were used to test associations of metabolomic profiles with anthropometric, clinical, and biochemical parameters. The analysis showed a serum amino acid signature composed of glycine, leucine, arginine, valine, and acylcarnitines associated with high VAI and low BMD. In addition, we found a sex-dependent VAI in pathways related to primary bile acid biosynthesis, branched-chain amino acids, and the biosynthesis of pantothenate and coenzyme A (CoA). In conclusion, a metabolic profile differs by VAI and BMD status, and these changes are gender-dependent.