Erros inatos do metabolismo confirmados no Hospital das Clínicas de Ribeirão Preto-SP no período de 2000 a 2008 / Inborn errors of metabolism in the Hospital of Clinics of Ribeirão Preto - SP from 2000 to 2008

Os Erros Inatos do Metabolismo (EIM) vêm sendo cada vez mais identificados nos últimos anos. A preocupação com o diagnóstico precoce decorre do foco na prevenção de deficiências, especialmente a mental. Este estudo descritivo teve por objetivo verificar diagnósticos confirmados e modalidades de tratamento utilizadas de janeiro de 2000 a dezembro de 2008. Método: foi realizada busca ativa de casos confirmados nos serviços que atendem esse tipo doença: neurologia (neuropediatria e doençasneuromusculares), pediatria (serviço de gastrologia e hepatologia) e genética clínica, além de levantamento no Serviço de Arquivo Médico do HCFMRP-USP. Foram confirmados 165 pacientes com EIM, com idades de um dia a 22 anos (mediana de um ano); 50 casos foram defeitos na síntese ou catabolismo de moléculas complexas, 65 no metabolismo intermediário, e 50 na produção ou utilização de energia. O tratamento foi instituído para 12 dos 50 pacientes do grupo I sendo reposição enzimática em 11 e transplante de medula óssea em um; todos do grupo II e III receberam orientação nutricional; 60 do grupo II receberam fórmula dietética industrializada; dos 50 do grupo III, 43 com mitocondriopatias receberam L-carnitina e coenzimas e aqueles com glicogenose, orientação sobre aporte de carbohidratos. A formação de novos recursos humanos, integração com a Rede EIM Brasil e linhas de pesquisa na área são prioridades para melhorar a acuidade na detecção e tratamento de erros inatos do metabolismo.

Inborn Errors of Metabolism have been increasingly identified in recent years. The early diagnosis focuses on prevention of disabilities, especially mental retardation. This descriptive study aims to verify confirmed diagnosis and treatment modalities in HCFMRP-USP cases from January of 2000 to December of 2008. A total of 165 patients with ages ranging from one day to 22 years (median one year) were detected. Fifty patients had synthesis or catabolism of complex molecules (group I), 65 intermediary metabolism (group II), and 50 had production or use of energy (group III) defects. Among the patients of group I, 11 had enzyme replacement therapy, and one bone marrow transplantation; for group II and III, inaddition to daily nutritional guidance for all of the patients, 60 from group II received industrialized diets; from group III, 43 with mitochondrial diseases received L-carnitine and coenzymes, and those with glycogenosis were focused mainly on the intake of carbohydrates. New human resources, integration with the Network EIM Brazil and lines of research in the area are priorities for improving the accuracy in the detection and treatment of inborn errors of metabolism.

Effects of L-arginine-enriched total enteral nutrition on body weight gain, tumor growth, and in vivo concentrations of blood and tissue metabolites in rats inoculated with Walker tumor in the kidney.

OBJECTIVE: We evaluated the effects of l-arginine-enriched total enteral nutrition (LATEN) on tumor-free and right kidney tumor-bearing rats through the determination of in vivo concentrations of metabolites to better understand intermediary metabolism in this model. METHODS: Rats were individually housed in wire cages within a controlled environment (25 degrees C and 50% relative humidity) and exposed to a 12-h light-and-dark cycle. Rats comprised the following groups: tumor-free on enteral nutrition plus l-amino acid (n = 8); tumor-free on enteral nutrition plus l-arginine (n = 8); tumor bearing on enteral nutrition plus l-amino acids (n = 8); and tumor bearing on enteral nutrition plus l-arginine (n = 8). Rats had their right kidneys inoculated with saline or tumor cells and were subjected to laparotomy or gastrostomy on day 1 and received chow diet for the next 2 days. Gastrostomy with enteral nutrition was performed on days 3 to 9. On day 9, body weight gain, tumor growth as volume, in vivo blood (microM/mL), and tissue (microM/g) metabolite concentrations were determined. The Mann-Whitney U test was used to test significance. RESULTS: LATEN in tumor-free rats decreased liver (0.25 +/- 0.03 versus 0.13 +/- 0.03 micromol/g, P < 0.05) and right kidney (0.13 +/- 0.1 versus 0.04 +/- 0.00 micromol/g, P < 0.05) ketone body concentrations. LATEN in tumor-bearing rats decreased blood pyruvate (0.17 +/- 0.01 versus 0.10 +/- 0.008 microM/mL, P < 0.005), lactate (5.2 +/- 0.3 versus 2.9 +/- 0.28 microM/mL, P < 0.01), and glucose (6.4 +/- 0.8 versus 3.7 +/- 0.5 microM/mL, P < 0.05). Glucose concentrations decreased in liver (13.9 +/- 2.0 versus 4.89 +/- 0.6 microM/g, P < 0.005) and tumor (3.5 +/- 0.8 versus 1.41 +/- 0.3 microM/g, P < 0.05). There were no changes in body weight gain (21 +/- 2.0 versus 30.3 +/- 3.6 g) or tumor growth (1.53 +/- 0.1 versus 1.26 +/- 0.01 cm(3)). CONCLUSIONS: LATEN decreased ketone body concentrations in liver and kidney in tumor-free rats, possibly due to lower ketogenesis and decreased kidney uptake. In tumor-bearing rats, LATEN decreased lacticemia and glycemia and pyruvate blood concentrations. LATEN also reduced liver and tumor glucose concentrations in tumor-bearing animals. The possibility of LATEN-induced insulin and insulin-like growth factor-1 liberation signaling these changes is discussed.