Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.308
Filtrar
1.
Medicine (Baltimore) ; 100(17): e25697, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33907148

RESUMO

RATIONALE: Transient infantile hypertriglyceridemia (HTGTI) is a rare autosomal recessive inherited disease caused by inactivating mutations in the glycerol-3-phosphate dehydrogenase 1 gene. To date, only a few patients have been reported worldwide. The symptoms of the affected individuals present a certain degree of transient hypertriglyceridemia, hepatomegaly, elevated liver enzymes, persistent fatty liver and hepatic fibrosis in early infancy. However, the clinical characteristics and pathogenesis of this disease are remain unclear. PATIENT CONCERNS: A one month and twenty-five days old girl was admitted to hospital because of persisted jaundice and hepatomegaly for fifty days. DIAGNOSE: The girl was diagnosed with HTGTI coincident with a noval mutation in glycerol-3-phosphate dehydrogenase 1. INTERVENTION: She was advised to take low-fat diet and supplement of medium-chain fatty acids. OUTCOMES: Her jaundice was gradually normal at the age of 4 months without any treatment, and hypertriglyceridemia were normal at the age of 13 months, but still had elevated transaminases and hepatic steatosis. LESSONS: Jaundice may be a novel phenotype in HTGTI. The report contributes to the expansion of HTGTI's gene mutation spectrum and its clinical manifestations.


Assuntos
Fígado Gorduroso , Glicerolfosfato Desidrogenase/genética , Hepatomegalia , Hipertrigliceridemia , Icterícia , Diagnóstico Diferencial , Dieta com Restrição de Gorduras/métodos , Fígado Gorduroso/diagnóstico , Fígado Gorduroso/etiologia , Feminino , Testes Genéticos/métodos , Hepatomegalia/diagnóstico , Hepatomegalia/etiologia , Humanos , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/genética , Lactente , Icterícia/diagnóstico , Icterícia/etiologia , Testes de Função Hepática , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Mutação , Transaminases/sangue
3.
Allergol. immunopatol ; 49(1): 101-106, ene.-feb. 2021. graf, tab
Artigo em Inglês | IBECS | ID: ibc-199232

RESUMO

BACKGROUND: Propionate inborn errors of metabolism (PIEM), including propionic (PA) and methylmalonic (MMA) acidemias, are inherited metabolic diseases characterized by toxic accumulation of propionic, 3-hydroxypropionic, methylcitric, and methylmalonic organic acids in biological fluids, causing recurrent acute metabolic acidosis events and encephalopathy, which can lead to fatal outcomes if managed inadequately. PIEM patients can develop hemato­logical abnormalities and immunodeficiency, either as part of the initial clinical presentation or as chronic complications. The origin and characteristics of these abnormalities have been studied poorly. Thus, the aim of the present work was to evaluate and describe lymphoid, myeloid, and erythroid cell population profiles in a group of clinically stable PIEM patients. METHODS: This was a retrospective study of 11 nonrelated Mexican PIEM patients. Clinical, bio­chemical, nutritional, hematological, and lymphocyte subsets were analyzed. RESULTS: Despite being considered clinically stable, 91% of patients had hematological or immu­nological abnormalities. The absolute lymphocyte subset counts were low in all patients but one, with CD4+ T-cell lymphopenia, being the most common one. Furthermore, of the 11 stud­ied subjects, nine presented with a low CD4/CD8 ratio. Among the observed hematological alterations, bicytopenia was the most common (82%) one, followed by anemia (27%). CONCLUSION: Our results contribute to the landscape of immunological abnormalities observed previously in PIEM patients; these abnormalities can become a life-threatening chronic com­plications because of the increased risk of opportunistic diseases. These findings allow us to propose the inclusion of monitoring immune biomarkers, such as subsets of lymphocytes in the follow up of PIEM patients


No disponible


Assuntos
Humanos , Masculino , Feminino , Lactente , Pré-Escolar , Criança , Erros Inatos do Metabolismo/terapia , Erros Inatos do Metabolismo/diagnóstico , Acidemia Propiônica/diagnóstico , Acidose/complicações , Acidemia Propiônica/terapia , México , Estudos Retrospectivos , Antígenos CD4/imunologia , Antígenos CD8/imunologia , Espectrometria de Massas/métodos , Citometria de Fluxo , Acidose/imunologia
4.
Ideggyogy Sz ; 74(1-2): 67-72, 2021 01 30.
Artigo em Inglês | MEDLINE | ID: mdl-33497052

RESUMO

Background and purpose: Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism. Methods: One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. The personal information, routine and specific metabolic tests of the patients were analyzed retrospectively. Results: Out of the 3261 patients who presented to our outpatient clinic, 179 (5.48%) were diagnosed with autism spectrum disorder and were included in the study. As a result of specific metabolic examinations performed, 6 (3.3%) patients were diagnosed with inborn errors of metabolism. Two of our patients were diagnosed with classical phenylketonuria, two with classical homocystinuria, one with mucopolysaccharidosis type 3D (Sanfilippo syndrome) and one with 3-methylchrotonyl Co-A carboxylase deficiency. Conclusion: Inborn errors of metabolism may rarely present with autism spectrum disorder symptoms. Careful evaluation of the history, physical examination and additional findings in patients diagnosed with autism spectrum disorder will guide the clinician in the decision-making process and chose the appropriate specific metabolic investigation. An underlying inborn errors of metabolism may be a treatable cause of autism.


Assuntos
Transtorno do Espectro Autista , Erros Inatos do Metabolismo , Transtorno do Espectro Autista/complicações , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Criança , Comorbidade , Humanos , Erros Inatos do Metabolismo/complicações , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/epidemiologia , Estudos Retrospectivos
5.
Rev Esp Salud Publica ; 952021 Jan 26.
Artigo em Espanhol | MEDLINE | ID: mdl-33496277

RESUMO

Newborn screening programs for congenital diseases aim to achieve a presymptomatic and early diagnosis of treatable disorders, in order to prevent or significantly reduce morbidity and/or mortality. Many of the conditions included in these programs are inborn errors of metabolism (IEM); however, the detection of endocrine, hematological, immunological, cardiovascular diseases, and congenital hearing loss are also included in many of them. Newborn screening tests are not diagnostic and therefore additional tests are needed to confirm or exclude the suspected diagnosis. The social and professional demand of the hand of the technological advances and new therapeutic options, allow the continuous expansion of neonatal screening; This progress has a clear benefit for patients, since thanks to the early diagnosis and treatment of their disease they can have a better prognosis and a better quality of life. The inclusion criteria of the different diseases should not be evaluated exclusively in function of the moment in which the evaluation is carried out, it is necessary to apply a long-term vision of opportunity based on the strengths of the health system. Today, after 50 years of experience, we can assure that neonatal screening programs constitute one of the most significant advances that have occurred in public health, their widespread practice has been one of the great achievements in pediatric healthcare and are marking the healthcare organization of many adult units. Hand in hand with advances in genetics and genomics, newborn screening programs will continue to expand for those disorders in which early intervention can significantly modify the course of the disease.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Medicina de Precisão , Humanos , Recém-Nascido , Avaliação de Programas e Projetos de Saúde , Espanha
6.
BMJ Case Rep ; 14(1)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33462045

RESUMO

Inherited pseudocholinesterase deficiency refers to an uncommon defect in the butyrylcholinesterase enzyme which can result in prolonged muscle paralysis due to delayed breakdown of choline ester paralytic anaesthetic agents. We describe a 25-year-old woman receiving electroconvulsive therapy (ECT) for treatment of depression in whom motor function did not recover adequately after administration of succinylcholine. Investigated post-ECT, she was found to have severe pseudocholinesterase deficiency. Implications of pseudocholinesterase deficiency for ECT treatment and anaesthetic strategies are discussed.


Assuntos
Apneia/diagnóstico , Butirilcolinesterase/deficiência , Transtorno Depressivo Maior/terapia , Eletroconvulsoterapia , Erros Inatos do Metabolismo/diagnóstico , Adulto , Feminino , Humanos
7.
Rev Esp Salud Publica ; 942020 Dec 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33323918

RESUMO

Galician newborn screening program for early detection of endocrine and metabolic diseases began in 1978 and was a pioneer in expanded newborn screening in Spain with the incorporation of mass spectrometry in July 2000. As a primary objective, 28 diseases are screened, including those recommended SNS except sickle cell anemia which is in the inclusion phase. In its 20-year history, 404,616 newborns (nb) have been analyzed, identifying 547 cases affected by the diseases included, with a global incidence of 1: 739 newborns and 1: 1.237 of the screened inborn errors of metabolism (IEM) (1:1.580 nb if excluding benign hyperphenylalaninemia-HPA), with an average participation of 99.35%, progressively higher during the analyzed period. Among the pathologies screened, congenital hypothyroidism (1:2.211 nb), cystinuria (1:4.129 nb) and HPA (1:5.699 nb), followed by phenylketonuria and cystic fibrosis (1:10,936 nb) stand out for their incidence. Sixty-six cases of false positives were identified (seventeen of them in relation to maternal pathology) and five false negatives, being the overall PPV and NPV of the program respectively of 89.2% and 99.99%, with a sensitivity of 99.09% and a specificity of 99.98%. The mortality rate of diagnosed CME patients is 1.52%, with eleven cases presenting symptoms prior to the screening result (2%). The intelligence quotient of IEM patients at risk of neurological involvement is normal in more than 95% of cases.


Assuntos
Hipotireoidismo Congênito/diagnóstico , Fibrose Cística/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Hipotireoidismo Congênito/epidemiologia , Fibrose Cística/epidemiologia , Reações Falso-Positivas , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/epidemiologia , Triagem Neonatal/métodos , Triagem Neonatal/normas , Triagem Neonatal/tendências , Avaliação de Programas e Projetos de Saúde , Sensibilidade e Especificidade , Espanha/epidemiologia
8.
Rev Esp Salud Publica ; 942020 Dec 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33323920

RESUMO

OBJECTIVE: The main justification of this study was to describe our experience in neonatal screening and to define the prevalence of the diseases included in the neonatal screening program in Andalusia, among which are congenital hypothyroidism, expanded screening (aminoacidopathies, mitochondrial beta-oxidation defects and organic acidurias), cystic fibrosis, and screening for sickle cell anemia. METHODS: The study was carried out in the Metabolopathies Unit of the Virgen del Rocío Hospital in Seville with samples of newborns from Western Andalusia (Cádiz, Córdoba, Huelva and Seville) and autonomous city of Ceuta. A total of 435,141 newborns were studied (from the period from April 1st 2009 to December 31st 2019) to rule out congenital hypothyroidism and expanded screening; 378,306 for cystic fibrosis from May 1st 2011 to the same date described above. Finally, sickle cell anemia screening was included, which comprised a total of 55,576 newborns from November 26th, 2018 to the same period as the previous ones. Statistical analysis was performed using IBM SPSS software (version 22, SPSS INC., USA). RESULTS: The study revealed a prevalence of 1:1565 newborns for congenital hypothyroidism, 1:1532 newborns for extended screening, 1:6.878 newborns for cystic fibrosis, and a 1:11.115 newborns for sickle cell disease. CONCLUSIONS: The neonatal screening program allows a large number of newborns to benefit from the early detection of certain serious congenital diseases. This aim improves the morbidity and mortality of those who suffer from them.


Assuntos
Anemia Falciforme/diagnóstico , Hipotireoidismo Congênito/diagnóstico , Fibrose Cística/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal , Anemia Falciforme/epidemiologia , Hipotireoidismo Congênito/epidemiologia , Fibrose Cística/epidemiologia , Diagnóstico Precoce , Humanos , Recém-Nascido , Estudos Longitudinais , Erros Inatos do Metabolismo/epidemiologia , Prevalência , Estudos Retrospectivos , Espanha/epidemiologia
9.
Rev Esp Salud Publica ; 942020 Dec 16.
Artigo em Espanhol | MEDLINE | ID: mdl-33323922

RESUMO

OBJECTIVE: Newborn screening programmes (NBSP) have experienced a qualitative breakthrough due to the implementation of tandem mass spectrometry. However, the tests used give rise to false positives (FP) generating an excessive request for second samples with the consequent anxiety of the families. In order to avoid this problem several programmes have developed second-tier tests (2TT). METHODS: This article presents our experience in the implementation of 2TT in the NBSP of Catalonia, as well as in other international programmes. RESULTS: From 2004 to the present, 2TT tests have been developed for more than 30 diseases. The use of 2TT helps to decrease the FP rate and increase the positive predictive value (PPV). In the NBSP of Catalonia, the implementation of 2TT for the detection of methylmalonic and propionic acidemias, homocystinurias, maple syrup disease and citrulinaemia, has managed to increase the PPV to 95% and decrease the PF rate to less than 0.01%. In cystic fibrosis, the application of 2TT slightly increases PPV but with a significant decrease in the request for second samples and in the number of cases referred to clinical units. CONCLUSIONS: The introduction of 2TT in the NBSP allows to reduce considerably the FP, decreases the number of requested samples, as well as both anxiety and stress of the families, at the same time that the hospital costs are reduced and the PPV is increased, improving notably the efficiency of the NBSP.


Assuntos
Fibrose Cística/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Imunodeficiência Combinada Severa/diagnóstico , Espectrometria de Massas em Tandem/métodos , Ansiedade/etiologia , Ansiedade/prevenção & controle , Biomarcadores/sangue , Fibrose Cística/sangue , Reações Falso-Positivas , Família/psicologia , Humanos , Recém-Nascido , Cooperação Internacional , Erros Inatos do Metabolismo/sangue , Triagem Neonatal/psicologia , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Imunodeficiência Combinada Severa/sangue , Espanha , Estresse Psicológico/etiologia , Estresse Psicológico/prevenção & controle
10.
Ann Biol Clin (Paris) ; 78(5): 547-554, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026349

RESUMO

Biochemical diagnosis of hereditary metabolic diseases requires the detection and simultaneous identification of a large number of compounds, hence the interest in metabolic profiles. Organic acid chromatography allows the identification of several hundred compounds and the quantification of the main molecules of interest. As part of the accreditation process for medical biology examinations according to standard NF EN ISO 15189, the group from the French society for inborn errors of metabolism (SFEIM) recommends an approach to accredit organic acid chromatography. Validation parameters and recommendations are discussed in this specific framework.


Assuntos
Ácidos/urina , Cromatografia Gasosa-Espectrometria de Massas/normas , Erros Inatos do Metabolismo/diagnóstico , Compostos Orgânicos/urina , Urinálise/normas , Acreditação , Ácidos/análise , Adulto , Bioquímica/métodos , Bioquímica/normas , Criança , Serviços de Laboratório Clínico/normas , Testes Diagnósticos de Rotina/métodos , Testes Diagnósticos de Rotina/normas , Feminino , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Recém-Nascido , Compostos Orgânicos/análise , Fase Pré-Analítica/métodos , Fase Pré-Analítica/normas , Gravidez , Urinálise/métodos , Coleta de Urina/métodos , Coleta de Urina/normas , Estudos de Validação como Assunto
11.
Ann Biol Clin (Paris) ; 78(5): 555-564, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33026350

RESUMO

Biochemical diagnosis of hereditary metabolic diseases requires the detection and simultaneous identification of a large number of compounds, hence the interest in metabolic profiles. Amino acid chromatography allows the identification and quantification of more than forty compounds. As part of the accreditation process for medical biology examinations according to standard NF EN ISO 15189, the group from SFEIM recommends an approach to accredit amino acid chromatography. Validation parameters and recommendations are discussed in this specific framework.


Assuntos
Aminoácidos/análise , Cromatografia/normas , Testes Diagnósticos de Rotina/normas , Erros Inatos do Metabolismo/diagnóstico , Acreditação/normas , Adulto , Aminoácidos/sangue , Aminoácidos/líquido cefalorraquidiano , Aminoácidos/urina , Amniocentese/normas , Líquido Amniótico/química , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Coleta de Amostras Sanguíneas/normas , Criança , Cromatografia/métodos , Cromatografia Líquida/normas , Testes Diagnósticos de Rotina/métodos , Feminino , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/líquido cefalorraquidiano , Erros Inatos do Metabolismo/urina , Triagem Neonatal/métodos , Triagem Neonatal/normas , Fase Pré-Analítica , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas , Espectrometria de Massas em Tandem/normas , Urinálise/métodos , Urinálise/normas , Coleta de Urina/normas
12.
Ann Biol Clin (Paris) ; 78(5): 537-546, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32933890

RESUMO

Biochemical diagnosis of hereditary metabolic diseases requires the detection and simultaneous identification of a large number of compounds, hence the interest in metabolic profiles. Acylcarnitine profile allows the identification and quantification of more than thirty compounds. As part of the accreditation process for medical biology examinations according to standard NF EN ISO 15189, the group from SFEIM recommends an approach to accredit acylcarnitine profile. Validation parameters and recommendations are discussed in this specific framework.


Assuntos
Carnitina/análogos & derivados , Serviços de Laboratório Clínico/normas , Testes Diagnósticos de Rotina/normas , Erros Inatos do Metabolismo/diagnóstico , Acreditação , Adulto , Amniocentese/métodos , Amniocentese/normas , Líquido Amniótico/química , Análise Química do Sangue/métodos , Análise Química do Sangue/normas , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/normas , Carnitina/análise , Carnitina/sangue , Carnitina/urina , Criança , Cromatografia em Papel/normas , Feminino , Humanos , Recém-Nascido , Masculino , Erros Inatos do Metabolismo/sangue , Erros Inatos do Metabolismo/urina , Triagem Neonatal/métodos , Triagem Neonatal/normas , Fase Pré-Analítica/métodos , Fase Pré-Analítica/normas , Gravidez , Diagnóstico Pré-Natal/métodos , Diagnóstico Pré-Natal/normas , Urinálise/métodos , Urinálise/normas , Coleta de Urina/métodos , Coleta de Urina/normas
14.
Nat Med ; 26(9): 1392-1397, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32778825

RESUMO

Public health newborn screening (NBS) programs provide population-scale ascertainment of rare, treatable conditions that require urgent intervention. Tandem mass spectrometry (MS/MS) is currently used to screen newborns for a panel of rare inborn errors of metabolism (IEMs)1-4. The NBSeq project evaluated whole-exome sequencing (WES) as an innovative methodology for NBS. We obtained archived residual dried blood spots and data for nearly all IEM cases from the 4.5 million infants born in California between mid-2005 and 2013 and from some infants who screened positive by MS/MS, but were unaffected upon follow-up testing. WES had an overall sensitivity of 88% and specificity of 98.4%, compared to 99.0% and 99.8%, respectively for MS/MS, although effectiveness varied among individual IEMs. Thus, WES alone was insufficiently sensitive or specific to be a primary screen for most NBS IEMs. However, as a secondary test for infants with abnormal MS/MS screens, WES could reduce false-positive results, facilitate timely case resolution and in some instances even suggest more appropriate or specific diagnosis than that initially obtained. This study represents the largest, to date, sequencing effort of an entire population of IEM-affected cases, allowing unbiased assessment of current capabilities of WES as a tool for population screening.


Assuntos
Exoma/genética , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/genética , Triagem Neonatal/métodos , Sequenciamento Completo do Exoma/métodos , Testes Genéticos , Humanos , Recém-Nascido , Erros Inatos do Metabolismo/epidemiologia , Espectrometria de Massas em Tandem
15.
Wiad Lek ; 73(6): 1211-1216, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32723955

RESUMO

OBJECTIVE: The aim: To compose an applicable diagnostic checklist for neonatologists, pediatricians, and general practitioners who refer newborns with certain inherited metabolic diseases (IMDs) suspicion to confirmatory testing laboratories. PATIENTS AND METHODS: Materials and methods: Analyzed international and generally, known national clinical guides and recommendations devoted to IMDs diagnostics, treatment and follow up. RESULTS: Results: Considering integral character of the diagnostic work-up of inborn errors of metabolism, authors of this article composed an applicable checklist that comprises set of data necessary for interpretation the positive results of expanded newborn screening and making decision of appropriate biochemical and molecular tests are required for confirmatory follow-up testing to establish the diagnosis and prescribe pathogenetic therapy. CONCLUSION: Conclusions: Properly filled checklist allow metabolic professionals to select appropriate confirmatory tests and interpret results obtained. Early IMDs diagnosis and prompt treatment initiation are crucial for positive outcomes and proved to be an effective tool to decrease levels of child disability and infant mortality.


Assuntos
Doenças Metabólicas/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Criança , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Triagem Neonatal , Pediatras
17.
Rev Med Suisse ; 16(695): 1120-1122, 2020 May 27.
Artigo em Francês | MEDLINE | ID: mdl-32462842

RESUMO

Patients come in consultation with a variety of complaints, some of which are unusual. We present here the case of a patient consulting for nauseating body odors for whom a diagnosis of trimethylaminuria could be found. This pathology, not very well known, may have important psychiatric and social repercussions. Genetics play a major role in diagnosis, while treatment consists essentially of various palliative measures.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/terapia , Metilaminas/urina , Humanos , Erros Inatos do Metabolismo/genética , Odorantes/análise
18.
BMC Med Genet ; 21(1): 79, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32295532

RESUMO

BACKGROUND: Congenital chloride diarrhea (CLD; OMIM 214700) is a rare autosomal recessive disorder caused by pathogenic variations in the solute carrier family 26 member A3 (SLC26A3) gene. Without salt substitution, this chronic diarrheal disorder causes severe dehydration and electrolyte disturbances. Homozygous variants in the nearby gene SLC26A4 disrupt anion exchange in the inner ear and the thyroid, causing Pendred syndrome (PDS; OMIM 274600), which is the most frequent form of syndromic deafness. CASE PRESENTATION: We report an unusual co-occurrence of two rare homozygous mutations in both the SLC26A3 and SLC26A4 genes, causing a rare combination of both CLD and PDS in two siblings. Although the clinical pictures were typical, the combined loss of these anion transporters might modulate the risk of renal injury associated with CLD. CONCLUSIONS: Familial presentation of two rare autosomal recessive disorders with loss of function of different SLC26 anion transporters is described. Independent homozygous variants in the SLC26A3 and SLC26A4 genes cause CLD and PDS in siblings, shedding light on co-occurrence of rare recessive traits in the progeny of consanguineous couples.


Assuntos
Antiportadores de Cloreto-Bicarbonato/genética , Diarreia/congênito , Bócio Nodular/genética , Perda Auditiva Neurossensorial/genética , Erros Inatos do Metabolismo/genética , Transportadores de Sulfato/genética , Diarreia/diagnóstico , Diarreia/genética , Diarreia/patologia , Feminino , Genes Recessivos/genética , Testes Genéticos , Bócio Nodular/diagnóstico , Bócio Nodular/patologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/patologia , Humanos , Lactente , Erros Inatos do Metabolismo/diagnóstico , Erros Inatos do Metabolismo/patologia , Mutação , Linhagem , Gravidez , Doenças Raras/diagnóstico , Doenças Raras/genética , Doenças Raras/patologia , Irmãos
19.
J Clin Endocrinol Metab ; 105(3)2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32126138

RESUMO

PURPOSE: Neonatal macrosomia is a known complication of maternal obesity and gestational diabetes, and it is a risk factor for obesity and diabetes in offspring. Amino acids and acylcarnitines are biomarkers for obesity in children and adults. These analytes, which are also routinely obtained on the newborn screen, have not been well-characterized in macrosomic newborns. The impact of macrosomia on rates of false-positive results in the newborn screen has also not been well-studied. We test the hypothesis that macrosomia is an interfering factor for amino acids and/or acylcarnitines on the newborn screen. METHODS: Newborn screening analytes determined by tandem mass spectroscopy were obtained from the Colorado Department of Public Health and Environment archives (2016-2018). This included metabolite concentrations obtained at 24-72 hours of life from newborns with birth weight 2500 to 3999 g (nonmacrosomic, n = 131 896) versus 4000 to 8000 g (macrosomic, n = 7806). Mother/infant phenotypic data were limited to information provided on the newborn screening dried blood spot card. Data were analyzed using Student t-test and chi-squared analysis. RESULTS: Macrosomic newborns had elevations in C2, C3, dicarboxylic, and long-chain acylcarnitines (specifically C16 and C18 species). C3 and C18:1 were 2 to 3 times more likely to be above predetermined state cutoffs in macrosomic versus nonmacrosomic newborns (both male and female). MAIN CONCLUSIONS: Macrosomia is an interfering factor for the analytes C3 and C18:1, leading to higher risk of false-positive results for methylmalonic/propionic acidemia and carnitine palmitoyl transferase type 2 deficiency, respectively. Analyte patterns found in macrosomic neonates correspond with similar analyte patterns in obese children and adults.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Carnitina O-Palmitoiltransferase/deficiência , Macrossomia Fetal/sangue , Doenças do Recém-Nascido/diagnóstico , Erros Inatos do Metabolismo/diagnóstico , Triagem Neonatal/métodos , Adulto , Carnitina/análogos & derivados , Carnitina/sangue , Colorado , Reações Falso-Positivas , Feminino , Macrossomia Fetal/complicações , Humanos , Recém-Nascido , Masculino , Obesidade Pediátrica/diagnóstico , Gravidez , Acidemia Propiônica/diagnóstico , Espectrometria de Massas em Tandem
20.
Int J Mol Sci ; 21(4)2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32054038

RESUMO

Early diagnosis of inborn errors of metabolism (IEM)-a large group of congenital disorders-is critical, given that many respond well to targeted therapy. Newborn screening programs successfully capture a proportion of patients enabling early recognition and prompt initiation of therapy. For others, the heterogeneity in clinical presentation often confuses diagnosis with more common conditions. In the absence of family history and following clinical suspicion, the laboratory diagnosis typically begins with broad screening tests to circumscribe specialised metabolite and/or enzyme assays to identify the specific IEM. Confirmation of the biochemical diagnosis is usually achieved by identifying pathogenic genetic variants that will also enable cascade testing for family members. Unsurprisingly, this diagnostic trajectory is too often a protracted and lengthy process resulting in delays in diagnosis and, importantly, therapeutic intervention for these rare conditions is also postponed. Implementation of mass spectrometry technologies coupled with the expanding field of metabolomics is changing the landscape of diagnosing IEM as numerous metabolites, as well as enzymes, can now be measured collectively on a single mass spectrometry-based platform. As the biochemical consequences of impaired metabolism continue to be elucidated, the measurement of secondary metabolites common across groups of IEM will facilitate algorithms to further increase the efficiency of diagnosis.


Assuntos
Erros Inatos do Metabolismo/diagnóstico , Metabolômica/métodos , Animais , Biomarcadores/análise , Biomarcadores/metabolismo , Quimioinformática/métodos , Diagnóstico Precoce , Humanos , Recém-Nascido , Aprendizado de Máquina , Espectrometria de Massas/métodos , Erros Inatos do Metabolismo/metabolismo , Metaboloma , Triagem Neonatal/métodos
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...