LONG TERM MANAGEMENT OF GLYCOGEN STORAGE DISEASE TYPE 1B: A BRAZILIAN TERTIARY CENTER EXPERIENCE.

BACKGROUND: Glycogen storage disease (GSD) type 1b is a multisystemic disease in which immune and infectious complications are present, in addition to the well-known metabolic manifestations of GSD. Treatment with granulocyte-colony stimulating factor (G-CSF) is often indicated in the management of neutropenia and inflammatory bowel disease. OBJECTIVE: To report on the demographics, genotype, clinical presentation, management, and complications of pediatric patients with glycogen storage disease type 1b (GSD 1b), with special attention to immune-related complications. METHODS: Retrospective case series of seven patients with GSD 1b diagnosed and followed at a tertiary university hospital in Brazil, from July/2000 until July/2016. RESULTS: Mean age at referral was fourteen months. Diagnosis of GSD 1b was based on clinical and laboratory findings and supported by genetic studies in five cases. All patients presented suffered from neutropenia, managed with G-CSF - specifically Filgrastim. Hospitalizations for infections were frequent. Two patients developed inflammatory bowel disease. Six patients remained alive, one died at age 14 years and 9 months. The mean age at the end of the follow-up was 11.5 years. Compliance to treatment was suboptimal: poor compliance to medications, starch and dietetic management of GSD were documented, and outpatient appointments were frequently missed. CONCLUSION: Managing GSD 1b is challenging not only for the chronic and multisystemic nature of this disease, but also for the additional demands related dietary restrictions, use of multiple medications and the need for frequent follow-up visits; furthermore in Brazil, the difficulties are increased in a scenario where we frequently care for patients with unfavorable socioeconomic status and with irregular supply of medications in the public health system.

ANTHROPOMETRIC AND DIETARY ASSESSMENT OF PATIENTS WITH GLYCOGENOSIS TYPE I.

OBJECTIVE: To perform anthropometric and dietary evaluation of patients with glycogenosis type Ia and Ib. METHODS: This cross-sectional study is composed of a sample of 11 patients with glycogenosis divided into two subgroups according to the classification of glycogenosis (type Ia=5 and type Ib=6), aged between 4 and 20 years. The analyzed anthropometric variables were weight, height, body mass index, and measures of lean and fat body mass, which were compared with reference values. For dietary assessment, a food frequency questionnaire was used to calculate energy and macronutrients intake as well as the amount of raw cornstarch consumed. Mann-Whitney U test and Fisher's exact test were performed, considering a significance level of 5%. RESULTS: Patients ingested raw cornstarch in the amount of 0.49 to 1.34 g/kg/dose at a frequency of six times a day, which is lower than recommended (1.75-2.50 g/kg/dose, four times a day). The amount of energy intake was, on average, 50% higher than energy requirements; however, carbohydrate intake was below the adequacy percentage in 5/11 patients. Short stature was found in 4/10 patients; obesity, in 3/11; and muscle mass deficit, in 7/11. There were no statistical differences between the subgroups. CONCLUSIONS: In patients with glycogenosis type I, there was deficit in growth and muscle mass, but no differences were found between the subgroups (Ia and Ib). Although the diet did not exceed the adequacy of carbohydrates, about 1/3 of the patients presented obesity, probably due to higher energy intake.

Anthropometric and dietary assessment of patients with glycogenosis type i / Avaliação antropométrica e dietética de pacientes com glicogenose tipo i

ABSTRACT Objective: To perform anthropometric and dietary evaluation of patients with glycogenosis type Ia and Ib. Methods: This cross-sectional study is composed of a sample of 11 patients with glycogenosis divided into two subgroups according to the classification of glycogenosis (type Ia=5 and type Ib=6), aged between 4 and 20 years. The analyzed anthropometric variables were weight, height, body mass index, and measures of lean and fat body mass, which were compared with reference values. For dietary assessment, a food frequency questionnaire was used to calculate energy and macronutrients intake as well as the amount of raw cornstarch consumed. Mann-Whitney U test and Fisher's exact test were performed, considering a significance level of 5%. Results: Patients ingested raw cornstarch in the amount of 0.49 to 1.34 g/kg/dose at a frequency of six times a day, which is lower than recommended (1.75-2.50 g/kg/dose, four times a day). The amount of energy intake was, on average, 50% higher than energy requirements; however, carbohydrate intake was below the adequacy percentage in 5/11 patients. Short stature was found in 4/10 patients; obesity, in 3/11; and muscle mass deficit, in 7/11. There were no statistical differences between the subgroups. Conclusions: In patients with glycogenosis type I, there was deficit in growth and muscle mass, but no differences were found between the subgroups (Ia and Ib). Although the diet did not exceed the adequacy of carbohydrates, about 1/3 of the patients presented obesity, probably due to higher energy intake.

RESUMO Objetivo: Realizar avaliação antropométrica e dietética de pacientes com glicogenose tipos Ia e Ib. Métodos: Estudo transversal composto de uma amostra de 11 pacientes com glicogenose divididos em dois subgrupos de acordo com a classificação da glicogenose (tipo Ia=5; tipo Ib=6), com idades entre 4 e 20 anos. As variáveis antropométricas analisadas foram peso, estatura, índice de massa corporal e medidas de massa magra e gorda, que foram comparadas com valores de referência. Para avaliação dietética, foi utilizado um questionário de frequência alimentar para cálculo de ingestão de energia e macronutrientes, além da quantidade de amido cru ingerida. Realizaram-se testes U de Mann-Whitney e exato de Fisher, com nível de significância de 5%. Resultados: Os pacientes ingeriram amido cru na quantidade de 0,49 a 1,34 g/kg/dose na frequência de seis vezes ao dia, inferior à dosagem preconizada (1,75-2,50 g/kg/dose quatro vezes ao dia). A quantidade de energia consumida foi, em média, 50% a mais que as necessidades, contudo o consumo de carboidratos foi abaixo da porcentagem de adequação em 5/11 pacientes. Baixa estatura ocorreu em 4/10 pacientes, obesidade em 3/11 e déficit de massa muscular em 7/11. Não houve diferença estatística entre os subgrupos. Conclusões: Em pacientes com glicogenose tipo I, houve déficit de crescimento e de massa muscular, mas não diferença significante entre os subgrupos (Ia e Ib). Embora a dieta não tenha ultrapassado a adequação de carboidratos, 1/3 dos pacientes apresentou obesidade, provavelmente pela maior ingestão de energia.

Pre and post-operative otorhinolaryngology surgery care in patients with glycogen storage disease type 1 / Cuidados pré e pós-operatórios em cirurgia otorrinolaringológica em pacientes com glicogenose tipo 1b

ABSTRACT Objective: To discuss aspects of pre and post-operative otorhinolaryngology surgery in patients with glycogen storage disease type 1b. Case description: Description of three clinical cases with probable glycogen storage disease type 1b who underwent otorhinolaryngology surgery, showing the importance of multidisciplinary interaction to avoid episodes of hypoglycemia. Comments: Patients with glycogen storage disease type 1b present recurrent infections, including the otorhinolaryngology affections. When there is an indication for surgical treatment, the caloric intake should be carefully followed in order to prevent hypoglycemia. The way to ensure this is to perform the pre and postoperative period in the hospital ward. In the postoperative period, it is important to make a slow transition between the intravenous and oral routes and not suspend the infusion of glucose during the surgical procedure. The cases illustrate the need for the interaction of the otorhinolaryngologic surgeon with the anesthesiologist, the pediatrician and the gastro-pediatrician in the management of these patients, avoiding hypoglycemic episodes.

RESUMO Objetivo: Discutir aspectos de pré e pós-operatório de cirurgia otorrinolaringológica em pacientes com glicogenose tipo 1b. Descrição do caso: Descrição de três casos clínicos com provável glicogenose tipo 1b, que se submeteram à cirurgia otorrinolaringológica, mostrando a importância da interação multidisciplinar para evitar os episódios de hipoglicemia. Comentários: Pacientes com glicogenose tipo 1b apresentam infecções de repetição, incluindo as otorrinolaringológicas. Quando há indicação de tratamento cirúrgico, deve-se observar a garantia de aporte calórico para evitar hipoglicemia. A maneira de fazer isso é efetuar o pré e pós-operatório em enfermaria, tomando-se o cuidado, no pós-operatório, de realizar uma transição lenta entre a via endovenosa e a via oral e de não suspender a infusão de glicose durante o procedimento cirúrgico. Os casos ilustram a necessidade da interação do otorrinolaringologista com o anestesista, o pediatra e o gastropediatra na condução desses pacientes para que não desenvolvam hipoglicemia.

PRE AND POST-OPERATIVE OTORHINOLARYNGOLOGY SURGERY CARE IN PATIENTS WITH GLYCOGEN STORAGE DISEASE TYPE 1.

OBJECTIVE: To discuss aspects of pre and post-operative otorhinolaryngology surgery in patients with glycogen storage disease type 1b. CASE DESCRIPTION: Description of three clinical cases with probable glycogen storage disease type 1b who underwent otorhinolaryngology surgery, showing the importance of multidisciplinary interaction to avoid episodes of hypoglycemia. COMMENTS: Patients with glycogen storage disease type 1b present recurrent infections, including the otorhinolaryngology affections. When there is an indication for surgical treatment, the caloric intake should be carefully followed in order to prevent hypoglycemia. The way to ensure this is to perform the pre and postoperative period in the hospital ward. In the postoperative period, it is important to make a slow transition between the intravenous and oral routes and not suspend the infusion of glucose during the surgical procedure. The cases illustrate the need for the interaction of the otorhinolaryngologic surgeon with the anesthesiologist, the pediatrician and the gastro-pediatrician in the management of these patients, avoiding hypoglycemic episodes.

Importância da biópsia hepática no diagnóstico da deficiência de lipase ácida lisossomal: relato de caso / Importance of liver biopsy in the diagnosis of lysosomal acid lipase deficiency: a case report

RESUMO Objetivo: Descrever a doença de depósito de ésteres de colesterol (DDEC) e a importância da biópsia hepática na realização do diagnóstico. Descrição do caso: Paciente feminina, dois anos e dez meses de idade, com queixa de aumento do volume abdominal secundário à hepatomegalia há quatro meses. Ultrassonografia abdominal demonstrou hepatomegalia e esteatose hepática. Exames laboratoriais mostraram aumento de enzimas hepáticas e dislipidemia. A biópsia hepática foi compatível com DDEC. Comentários: Embora a medida da atividade enzimática seja o padrão-ouro para o diagnóstico de DDEC, a biópsia hepática é muito útil na investigação de casos suspeitos, particularmente quando há outros diagnósticos diferenciais a serem considerados.

ABSTRACT Objective: To describe a case of cholesteryl ester storage disease (CESD) and discuss the importance of liver biopsy for diagnosis. Case description: A female patient, aged two years and ten months, presented with an increased abdominal volume following hepatomegaly for four months. Abdominal ultrasound demonstrated hepatomegaly and hepatic steatosis. Laboratory tests showed elevated liver serum enzymes and dyslipidemia. Liver biopsy was consistent with CESD. Comments: Although measuring enzyme activity is the gold standard for CESD diagnosis, liver biopsy is very helpful when investigating suspected cases of CESD, particularly upon other differential diagnoses to be considered.

IMPORTANCE OF LIVER BIOPSY IN THE DIAGNOSIS OF LYSOSOMAL ACID LIPASE DEFICIENCY: A CASE REPORT. / IMPORTÂNCIA DA BIÓPSIA HEPÁTICA NO DIAGNÓSTICO DA DEFICIÊNCIA DE LIPASE ÁCIDA LISOSSOMAL: RELATO DE CASO.

OBJECTIVE: To describe a case of cholesteryl ester storage disease (CESD) and discuss the importance of liver biopsy for diagnosis. CASE DESCRIPTION: A female patient, aged two years and ten months, presented with an increased abdominal volume following hepatomegaly for four months. Abdominal ultrasound demonstrated hepatomegaly and hepatic steatosis. Laboratory tests showed elevated liver serum enzymes and dyslipidemia. Liver biopsy was consistent with CESD. COMMENTS: Although measuring enzyme activity is the gold standard for CESD diagnosis, liver biopsy is very helpful when investigating suspected cases of CESD, particularly upon other differential diagnoses to be considered.

OBJETIVO: Descrever a doença de depósito de ésteres de colesterol (DDEC) e a importância da biópsia hepática na realização do diagnóstico. DESCRIçÃO DO CASO: Paciente feminina, dois anos e dez meses de idade, com queixa de aumento do volume abdominal secundário à hepatomegalia há quatro meses. Ultrassonografia abdominal demonstrou hepatomegalia e esteatose hepática. Exames laboratoriais mostraram aumento de enzimas hepáticas e dislipidemia. A biópsia hepática foi compatível com DDEC. COMENTÁRIOS: Embora a medida da atividade enzimática seja o padrão-ouro para o diagnóstico de DDEC, a biópsia hepática é muito útil na investigação de casos suspeitos, particularmente quando há outros diagnósticos diferenciais a serem considerados.

Atresia biliar: a experiência Brasileira / Biliary atresia: the Brazilian experience

OBJETIVO: Avaliar as características epidemiológicas, clínicas e prognósticas de crianças com atresia biliar. MÉTODOS: Dados sobre portoenterostomia, transplante hepático (TxH), idade no último seguimento e sobrevida foram coletados dos prontuários de pacientes acompanhados em seis centros no Brasil (1982-2008) e comparados em relação às décadas do procedimento cirúrgico. RESULTADOS: Dos 513 pacientes, 76,4 por cento foram submetidos a portoenterostomia [idade: 60,0-94,7 (82,6±32,8) dias] e 46,6 por cento foram submetidos a TxH. Em 69 por cento dos casos, o TxH foi realizado após a portoenterostomia, enquanto em 31 por cento dos casos o TxH foi realizado como cirurgia primária. Os pacientes da região Nordeste foram submetidos a portoenterostomia mais tardiamente do que as crianças das regiões Sul (p = 0,008) e Sudeste (p = 0,0012), embora, mesmo nas duas últimas regiões, a idade no momento da portoenterostomia tenha sido superior ao desejável. Ao longo das décadas, houve aumento progressivo do número de TxH realizados. A sobrevida global foi de 67,6 por cento. A sobrevida aumentou nas últimas décadas (anos 1980 versus 1990, p = 0,002; anos 1980 versus 2000, p < 0,001; anos 1990 versus 2000, p < 0,001). A sobrevida de 4 anos pós-portoenterostomia, com ou sem TxH, foi de 73,4 por cento, inversamente correlacionada à idade no momento da portoenterostomia (80, 77,7, 60,5 por cento para < 60, 61-90, > 90 dias, respectivamente). Os pacientes transplantados apresentaram taxas de sobrevida mais elevadas (88,3 por cento). A sobrevida de 4 anos com fígado nativo foi de 36,8 por cento, inversamente correlacionada à idade no momento da portoenterostomia (54, 33,3, 26,6 por cento para < 60, 61-90, > 90 dias, respectivamente). CONCLUSÕES: Este estudo multicêntrico demonstrou que o encaminhamento tardio das crianças portadoras de atresia biliar ainda é um problema no Brasil, influenciando a sobrevida destes pacientes. Estratégias que proporcionam o encaminhamento precoce estão sendo desenvolvidas com o objetivo de reduzir a necessidade de transplante hepático nos primeiros anos de vida.

OBJECTIVE: To evaluate epidemiological, clinical and prognostic characteristics of children with biliary atresia. METHODS: Data regarding portoenterostomy, liver transplantation (LTx), age at last follow-up and survival were collected from the records of patients followed up in six Brazilian centers (1982-2008) and compared regarding decades of surgery. RESULTS: Of 513 patients, 76.4 percent underwent portoenterostomy [age: 60-94.7 (82.6±32.8) days] and 46.6 percent underwent LTx. In 69 percent of cases, LTx followed portoenterostomy, whereas in 31 percent of cases LTx was performed as the primary surgery. Patients from the Northeast region underwent portoenterostomy later than infants from Southern (p = 0.008) and Southeastern (p = 0.0012) Brazil, although even in the latter two regions age at portoenterostomy was higher than desirable. Over the decades, LTx was increasingly performed. Overall survival was 67.6 percent. Survival increased over the decades (1980s vs. 1990s, p = 0.002; 1980s vs. 2000s, p < 0.001; 1990s vs. 2000s, p < 0.001). The 4-year post-portoenterostomy survival, with or without LTx, was 73.4 percent, inversely correlated with age at portoenterostomy (80, 77.7, 60.5 percent for < 60, 61-90, > 90 days, respectively). Higher survival rates were observed among transplanted patients (88.3 percent). The 4-year native liver survival was 36.8 percent, inversely correlated with age at portoenterostomy (54, 33.3, 26.6 percent for < 60, 61-90, > 90 days, respectively). CONCLUSIONS: This multicenter study showed that late referral for biliary atresia is still a problem in Brazil, affecting patient survival. Strategies to enhance earlier referral are currently being developed aiming to decrease the need for liver transplantation in the first years of life.

Clinical and biochemical features of autoimmune hepatitis in 36 pediatric patients

RACIONAL: Poucos estudos sobre hepatite autoimune têm sido conduzidos em pacientes não-caucasianos. OBJETIVOS: Avaliar crianças brasileiras com hepatite autoimune tipos 1 e 2 em relação à evolução clínica e parâmetros clínicos e bioquímicos. MÉTODOS: Trinta e seis pacientes foram incluídos em um protocolo que registrou os dados da história clínica, exame físico, dados bioquímicos e evolução da doença. Vinte e quatro crianças tinham hepatite autoimune tipo 1, sete pacientes hepatite autoimune tipo 2 e em cinco casos, a hepatite autoimune não pôde ser classificada. A maioria dos pacientes pertencia ao sexo feminino (77%), a mediana de idade ao diagnóstico foi de 11 anos e a mediana de duração dos sintomas foi de 5,5 e 8 meses, para os tipos 1 e 2, respectivamente. Icterícia e colúria foram as manifestações clínicas mais freqüentes. RESULTADOS: A terapia com azatioprina e prednisona foi eficaz para os pacientes com os tipos 1 ou 2 de hepatite. As enzimas AST e ALT apresentaram decréscimo em relação aos valores no diagnóstico, após 4 a 8 semanas de tratamento, nos pacientes com hepatite autoimune do tipo 1. Os valores de GGT tornaram-se mais elevados após o início da terapia e retornaram aos níveis pré-tratamento após 1 ano, nos dois tipos de hepatite. Três pacientes foram a óbito e outros três realizaram transplante hepático. CONCLUSÕES: Crianças não-caucasianas apresentaram doença semelhante a pacientes caucasianos com hepatite autoimune. Níveis elevados de GGT no primeiro ano de tratamento não devem ser o único marcador da existência de colangiopatia.