Biochemical and Molecular Chitotriosidase Profiles in Patients with Gaucher Disease Type 1 in Minas Gerais, Brazil: New Mutation in CHIT1 Gene.

Chitotriosidase (ChT) is a human chitinase secreted by activated macrophages and its activity is used in therapeutic monitoring of Gaucher disease (GD), the most common lysosomal storage disease. About 6% of the population is homozygous for a duplication of 24 bp in exon 11 of the CHIT1 gene (dup24), which is the main polymorphism that results in the absence of ChT. As ChT enzyme activity can be used as a biomarker in GD, it is important to know the CHIT1 genotype of each patient. In this study, ChT activity and CHIT1 genotype were evaluated in 33 GD type 1 patients under treatment in the state of Minas Gerais, Brazil, and compared to healthy controls. As expected, the enzyme activity was found to be higher in GD type 1 patients than in healthy subjects. Four patients had no ChT activity. Their genotype revealed three patients (9%) homozygous for dup24 allele and one patient with two polymorphisms in exon 11: G354R and a 4 bp deletion at the exon-intron 11 boundary (g.16993_16996delGAGT), the later described for the first time in literature. Two other patients with lower ChT activity presented a polymorphism in exon 4 (c.304G>A, p.G102S), without dup24 allele. In conclusion, this study demonstrated that ChT activity can be used for therapeutic monitoring in 82% of GD patients of the state of Minas Gerais, Brazil.

Linfoma não-Hodgkin em crianças com imunodeficiência: relato de cinco casos / Non-Hodgkin's lymphoma in children with immunodeficiency: report of five cases

Neste estudo é relatado o quadro clínico de cinco crianças com linfoma não-Hodgkin secundário a imunodeficiência ou imunossupressão: três portadoras do vírus da imunodeficiência humana, uma com imunodeficiência primária e uma após transplante hepático. De acordo com a classificação atual, os tipos histológicos foram: linfoma linfoblástico de células B precursoras (2), linfoma cutâneo de grandes células anaplásico (1), linfoma de células B periféricas, sugestivo de Burkitt (1), e linfoma linfoblástico de células T precursoras (1). Todos os pacientes foram submetidos a quimioterapia, sendo que dois estão em remissão clínica, dois morreram e um continua em tratamento. Após a introdução da terapia anti-retroviral combinada e o aumento dos transplantes de órgãos sólidos ocorre maior risco de neoplasia nesses pacientes. Desse modo, é importante o seguimento desses pacientes para determinar os fatores de risco para o desenvolvimento de neoplasias e definir adequada estratégia de tratamento.

The outcomes of five children with non-Hodgkin's lymphomas associated with immunodeficiency or immunosuppression is reported: three children with HIV, one with primary immunodeficiency and one after liver transplantation. According to the REAL classification, two patients had precursor B-lymphoblastic lymphomas, one had an anaplastic large cell lymphoma, one had a peripheral B-cell neoplasm suggestive of Burkitt's lymphoma, and one had precursor T-lymphoblastic lymphoma. All patients received chemotherapy. Two are in complete remission, two died and one remains under treatment. There has been an increasing awareness of the risk of non-Hodgkin's lymphoma and lymphoproliferative disorders after active antiretroviral therapy and with the expansion of solid organ transplant programs in the pediatric setting. Thus, for these patients it is important to establish risk factors for hematological disorders and determine the optimal and safest treatment.

Clinical course of autoimmune hemolytic anemia: an observational study.

OBJECTIVE: Autoimmune hemolytic anemia is characterized by the production of autoantibodies against erythrocyte membrane antigens. This study was carried out to identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG) Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS: We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS: The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients), followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkin's lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months). Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION: Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

Clinical course of autoimmune hemolytic anemia: an observational study

OBJECTIVE: Autoimmune hemolytic anemia is characterized by the production of autoantibodies against erythrocyte membrane antigens. This study was carried out to identify the clinical, immunological and outcome characteristics of autoimmune hemolytic anemia patients treated at the (HC-UFMG) Pediatric Hematology Unit and the Hemocentro de Belo Horizonte. METHODS: We evaluated 17 patients younger than 15 years old admitted from 1988 to 2003 were evaluated. Autoimmune hemolytic anemia diagnosis was based on the presence of acquired hemolysis and confirmed by positive direct Coombs polyspecific test results. Clinical, laboratory, and outcome data were obtained from patient records. RESULTS: The median age at diagnosis was 10.5 months. The direct Coombs polyspecific test was positive in 13 and negative in four patients. Monospecific testing was performed for 14 patients. The most frequent red cell autoantibody was IgG (five patients), followed by IgM in two. Thirteen patients had severe anemia and needed blood transfusions. Underlying diseases were identified in four patients: systemic lupus erythematosus, Hodgkin's lymphoma, autoimmune hepatitis and Langerhans cell histiocytosis. The remaining patients were classified as having primary disease. The median follow-up period was 11 months (5 to 23 months). Three children died, two after splenectomy and one with complications of the underlying disease. CONCLUSION: Autoimmune hemolytic anemia is rare in children and adolescents. Although patients usually respond to corticosteroids and/or immunoglobulin, fatal cases can occur. Prognosis is worse in patients with chronic underlying diseases.

[Clinical and nutritional aspects of Gaucher disease: prospective study of 13 children at a single center]. / Aspectos clínicos e nutricionais da doença de Gaucher: estudo prospectivo de 13 crianças em um único centro.

OBJECTIVE: Gaucher disease is an autosomal recessive lysosomal storage disease, caused by mutation to the GBA gene (glucocerebrosidase gene) located on chromosome 1. The objective of the present study was to identify the clinical, nutritional, biochemical and genetic features of the patients with Gaucher disease treated at the Unit of Pediatric Hematology (Hospital das Clínicas-Universidade Federal de Minas Gerais). METHODS: Thirteen patients were prospectively followed up. Gaucher disease was confirmed in all patients through the use of an enzyme assay test to measure glucocerebrosidase enzyme activity. Demographic and nutritional data, and biochemical findings obtained on admission, were studied. Genetic testing was performed in seven patients. The median age of follow-up was 5.3 years. Z scores for weight and height on admission and at the end of observation period were calculated. The standardized prevalence for malnutrition was calculated using the Mora method. RESULTS: The mean age at diagnosis was 5.8 years. The predominant clinical manifestations at diagnosis were hepatomegaly and splenomegaly, and all patients were classified as clinical type 1. Low platelet count and anemia were detected at diagnosis in eight and six children, respectively. The most frequent genetic mutation was N370S. One child died during follow-up due to septicemia, after splenectomy. The prevalence of malnutrition was 26% at admission and 48% at the end of the observation period. CONCLUSION: The analysis of data demonstrates that N370S and clinical type 1 predominate in our Unit, characterizing the milder form of the disease. The irregular enzyme replacement therapy during the study period did not allow valid clinical conclusions on its efficacy.

Estudo de doenças de má absorçäo intestinal como causa de baixa estatura monossintomática / Study of intestinal malabsorption diseases as cause of monosymptomatic short stature

Objetivo: Este estudo foi realizado com o objetivo de avaliar causas de baixa estatura monossintomática na infância, enfatizando causas de má-absorçäo intestinal, especialmente doença celíaca. Métodos: Foram avaliadas, em um desenho transversal, crianças com estatura abaixodo terceiro percentil ou taxa de crescimento inferior a 5cm/ano. A seguinte propedêutica foi realizada: avaliaçäo hematológica, bioquímica, endocrinológica, idade óssea, pesquisa sorológica de anticorpos antigliadina, gordura fecal, dosagem de cloretos no suor e biópsia jejunal. Resultados: Um total de 51 crianças foi estutado, sendo que a maioria foi incluída no grupo dos variantes da normalidade. Näo foram encontradas portadoras de doença celíaca, mas identificaram-se 4 crianças com provável fibrose cística, assintomáticas em relaçäo ao trato respiratório e gastrintestinal. Conclusäo: Além da doença celíaca, a fibrose cística deve ser incluída no diagnóstico diferencial de baixa estatura na infância...