Avaliação clínica, metabólica e molecular de pacientes com acidemias orgânicas
Arquivos
Data
2023-07-27
Autores
Silva, José Araújo de Oliveira 
Orientadores
D'Almeida, Vânia
Tipo
Tese de doutorado
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ISSN da Revista
Título de Volume
Resumo
Introdução: As acidemias orgânicas (AOs) são doenças metabólicas hereditárias devidas à deficiência de uma enzima ou proteína de transporte envolvidas em uma das várias vias metabólicas celulares dedicadas ao catabolismo de aminoácidos, carboidratos ou lipídios. Não há dados oficiais brasileiros sobre a incidência dessas doenças na população. O diagnóstico precoce das AOs é fundamental para evitar descompensações que prejudiquem o desenvolvimento global dos pacientes, e especialmente no sistema nervoso central. Objetivo: Caracterizar uma amostra de pacientes com AOs do Centro de Referência em Erros Inatos do Metabolismo da Universidade Federal de São Paulo (CREIM/UNIFESP) do ponto de vista clínico, nutricional e molecular. Método: Estudo do tipo transversal, com análise de dados clínicos, bioquímicos e moleculares por meio de coleta de sangue e urina. Dados dietéticos foram analisadas por meio de recordatório alimentar de 3 dias. Análise molecular realizada por meio de sequenciamento de nova geração. As análises estatísticas descritivas foram feitas por meio de inferência e as variáveis e suas comparações por meio do teste-t de Student. Resultados: A amostra constou de 75 participantes diagnosticados com 11 acidemias orgânicas. Destes, 34% (n=26) foram diagnosticados por meio de análise de ácidos orgânicos, 17,3% (n=13) pelo perfil de acilcarnitinas e 14,6% (n=11) por espectrometria de massas em tandem. A mediana do tempo em tratamento foi de 6 anos (intervalo de 2 dias a 28 anos). A mediana de idade de início dos sintomas/sinais foi de 11 dias, o intervalo de aparecimento de sintomas esteve entre 0 e 720 dias. O valor de mediana do diagnóstico foi de 360 dias (intervalo de 2 a 13.500 dias). O sintoma mais prevalente foi atraso do desenvolvimento neuropsicomotor 56% (n=42), hipoglicemia ocorreu em 20% (n=15) dos casos, seguida de náuseas e vômitos 18% (n=14), e convulsão em 13% (n=10). O Índice de Massa Corpórea para Idade (IMC/I) foi avaliado em 72 pacientes (96%), sendo 61,5% (n=32) apresentavam eutrofia, 17,3% (n=9) risco de sobrepeso, 7,6% (n=4) sobrepeso, 3,8% (n=2) estavam na faixa de magreza, 5,7% em extrema magreza e 1,92% (n=1) em obesidade grave. Não houve diferença estatisticamente significante entre estes parâmetros (p=0,39). A prescrição dietética ocorreu em 71 pacientes visando à diminuição do metabólito tóxico. Para pacientes com restrição de proteína (n=70), a prescrição de fórmula de aminoácidos e/ou metabólica foi indicada em 42 (60%) pacientes sendo eles: Maple Syrup Urine Disease (MSUD)=24, acidemia metilmalônica (MMA)=11, acidemia propiônica (PA)=3, acidemia glutárica (GA1)= 3 e Acidemia 3-hidroxi-3- metilglutárica=1. A ingestão dos aminoácidos se mostrou abaixo do recomendado em 16 pacientes, sendo: GA1 (n=5), MSUD (n=3), PA (n=2), acidemia isovalérica (n=1) e MMA (n=5). Em todos a ingestão de fibra estava abaixo do recomendado. As alterações ao longo do tratamento aconteceram em sua maior parte em relação à série vermelha, ferro sérico, ferritina, selênio e vitamina D. A análise molecular ocorreu em 20 pacientes. Variantes foram encontradas em 13 pacientes, sendo 5 (25%) em homozigose e 8 (40%) em heterozigose. Todas variantes já descritas na literatura. Conclusão: Nossos achados mostram que o acompanhamento assistencial, multidisciplinar e bioquímico dos pacientes com acidemias orgânicas ainda é desafiador para profissionais e serviços de saúde, o que mostra a importância de mais estudos com essa população visando ao diagnóstico precoce e permitindo a melhora do prognóstico desses pacientes.
Introduction: Organic acidemias (AOs) are hereditary metabolic diseases due to the deficiency of an enzyme or transport protein involved in one of several cellular metabolic pathways dedicated to the catabolism of amino acids, carbohydrates or lipids. There are no official Brazilian data on the incidence of these diseases in the population. Early diagnosis of AOs is essential to avoid decompensations that harm the overall development of patients, and especially in the central nervous system. Objective: To characterize a sample of patients with AOs from the Reference Center for Inborn Errors of Metabolism at the Federal University of São Paulo (CREIM/UNIFESP) from a clinical, nutritional and molecular point of view. Method: Crosssectional study, with analysis of clinical, biochemical and molecular data through blood and urine collection. Dietary data were analyzed using a 3day dietary recall. Molecular analysis performed using nextgeneration sequencing. Descriptive statistical analyzes were performed using inference and variables and their comparisons using Student's ttest. Results: The sample consisted of 75 participants diagnosed with 11 organic acidemias. Of these, 34% (n=26) were diagnosed by organic acid analysis, 17.3% (n=13) by acylcarnitine profile, and 14.6% (n=11) by tandem mass spectrometry. The median time on treatment was 6 years (range 2 days to 28 years). The median age of onset of symptoms/signs was 11 days, the interval between the onset of symptoms was between 0 and 720 days. The median value of the diagnosis was 360 days (range 2 to 13,500 days). The most prevalent symptom was delayed neuropsychomotor development in 56% (n=42), hypoglycemia occurred in 20% (n=15) of cases, followed by nausea and vomiting in 18% (n=14), and seizures in 13% (n=15). =10). The Body Mass Index for Age (BMI/A) was assessed in 72 patients (96%), of which 61.5% (n=32) had normal weight, 17.3% (n=9) at risk of overweight, 7, 6% (n=4) were overweight, 3.8% (n=2) were in the thin range, 5.7% were extremely thin and 1.92% (n=1) were severely obese. There was no statistically significant difference between these parameters (p=0.39). Dietary prescription was given to 71 patients with a view to reducing the toxic metabolite. For patients with protein restriction (n=70), the prescription of an amino acid and/or metabolic formula was indicated in 42 (60%) patients, namely: Maple Syrup Urine Disease (MSUD)=24, methylmalonic acidemia (MMA)= 11, propionic acidemia (PA=3), glutaric acidemia (GA1)=3 and 3hydroxy3methylglutaric acidemia=1. Amino acid intake was below the recommended level in 16 patients, namely: GA1 (n=5), MSUD (n=3), BP (n=2), isovaleric acidemia (n=1) and MMA (n=5). In all, fiber intake was below the recommended level. Changes during treatment mostly occurred in relation to the red series, serum iron, ferritin, selenium and vitamin D. Molecular analysis was carried out in 20 patients. Variants were found in 13 patients, 5 (25%) homozygous and 8 (40%) heterozygous. All variants already described in the literature. Conclusion: Our findings show that the care, multidisciplinary and biochemical followup of patients with organic acidemia is still challenging for health professionals and services, which shows the importance of further studies with this population aimed at early diagnosis and allowing the improvement of the prognosis of these patients. patients.
Introduction: Organic acidemias (AOs) are hereditary metabolic diseases due to the deficiency of an enzyme or transport protein involved in one of several cellular metabolic pathways dedicated to the catabolism of amino acids, carbohydrates or lipids. There are no official Brazilian data on the incidence of these diseases in the population. Early diagnosis of AOs is essential to avoid decompensations that harm the overall development of patients, and especially in the central nervous system. Objective: To characterize a sample of patients with AOs from the Reference Center for Inborn Errors of Metabolism at the Federal University of São Paulo (CREIM/UNIFESP) from a clinical, nutritional and molecular point of view. Method: Crosssectional study, with analysis of clinical, biochemical and molecular data through blood and urine collection. Dietary data were analyzed using a 3day dietary recall. Molecular analysis performed using nextgeneration sequencing. Descriptive statistical analyzes were performed using inference and variables and their comparisons using Student's ttest. Results: The sample consisted of 75 participants diagnosed with 11 organic acidemias. Of these, 34% (n=26) were diagnosed by organic acid analysis, 17.3% (n=13) by acylcarnitine profile, and 14.6% (n=11) by tandem mass spectrometry. The median time on treatment was 6 years (range 2 days to 28 years). The median age of onset of symptoms/signs was 11 days, the interval between the onset of symptoms was between 0 and 720 days. The median value of the diagnosis was 360 days (range 2 to 13,500 days). The most prevalent symptom was delayed neuropsychomotor development in 56% (n=42), hypoglycemia occurred in 20% (n=15) of cases, followed by nausea and vomiting in 18% (n=14), and seizures in 13% (n=15). =10). The Body Mass Index for Age (BMI/A) was assessed in 72 patients (96%), of which 61.5% (n=32) had normal weight, 17.3% (n=9) at risk of overweight, 7, 6% (n=4) were overweight, 3.8% (n=2) were in the thin range, 5.7% were extremely thin and 1.92% (n=1) were severely obese. There was no statistically significant difference between these parameters (p=0.39). Dietary prescription was given to 71 patients with a view to reducing the toxic metabolite. For patients with protein restriction (n=70), the prescription of an amino acid and/or metabolic formula was indicated in 42 (60%) patients, namely: Maple Syrup Urine Disease (MSUD)=24, methylmalonic acidemia (MMA)= 11, propionic acidemia (PA=3), glutaric acidemia (GA1)=3 and 3hydroxy3methylglutaric acidemia=1. Amino acid intake was below the recommended level in 16 patients, namely: GA1 (n=5), MSUD (n=3), BP (n=2), isovaleric acidemia (n=1) and MMA (n=5). In all, fiber intake was below the recommended level. Changes during treatment mostly occurred in relation to the red series, serum iron, ferritin, selenium and vitamin D. Molecular analysis was carried out in 20 patients. Variants were found in 13 patients, 5 (25%) homozygous and 8 (40%) heterozygous. All variants already described in the literature. Conclusion: Our findings show that the care, multidisciplinary and biochemical followup of patients with organic acidemia is still challenging for health professionals and services, which shows the importance of further studies with this population aimed at early diagnosis and allowing the improvement of the prognosis of these patients. patients.
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Citação
SILVA, José Araújo de Oliveira. Avaliação clínica, metabólica e molecular de pacientes com acidemias orgânicas. 2023. 116 f. Tese (Doutorado em Pediatria e Ciências Aplicadas à Pediatria) - Escola Paulista de Medicina, Universidade Federal de São Paulo (UNIFESP), São Paulo, 2023.